Therapeutic agents useful for treating pain

Abstract
A compound of formula:
Description
REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

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1. FIELD OF THE INVENTION

The present invention relates to Cyclo(hetero)alkenyl Compounds, compositions comprising an effective amount of a Cyclo(hetero)alkenyl Compound and methods for treating or preventing a condition such as pain comprising administering to an animal in need thereof an effective amount of a Cyclo(hetero)alkenyl Compound.


2. BACKGROUND OF THE INVENTION

Pain is the most common symptom for which patients seek medical advice and treatment. Pain can be acute or chronic. While acute pain is usually self-limited, chronic pain persists for 3 months or longer and can lead to significant changes in a patient's personality, lifestyle, functional ability and overall quality of life (K. M. Foley, Pain, in Cecil Textbook of Medicine 100-107 (J. C. Bennett and F. Plum eds., 20th ed. 1996)).


Moreover, chronic pain can be classified as either nociceptive or neuropathic. Nociceptive pain includes tissue injury-induced pain and inflammatory pain such as that associated with arthritis. Neuropathic pain is caused by damage to the peripheral or central nervous system and is maintained by aberrant somatosensory processing. There is a large body of evidence relating activity at both Group I metabotropic glutamate receptors (mGluR1 and mGluR5) (M. E. Fundytus, CNS Drugs 15:29-58 (2001)) and vanilloid receptors (VR1) (V. Di Marzo et al., Current Opinion in Neurobiology 12:372-379 (2002)) to pain processing. Inhibiting mGluR1 or mGluR5 reduces pain, as shown by in vivo treatment with antibodies selective for either mGluR1 or mGluR5, where neuropathic pain in rats was attenuated (M. E. Fundytus et al., NeuroReport 9:731-735 (1998)). It has also been shown that antisense oligonucleotide knockdown of mGluR1 alleviates both neuropathic and inflammatory pain (M. E. Fundytus et al., Brit. J. Pharmacol. 132:354-367 (2001); M. E. Fundytus et al., Pharmacol., Biochem. & Behavior 73:401-410 (2002)). Small molecule antagonists for mGluR5-attenuated pain in in vivo animal models are disclosed in, e.g., K. Walker et al., Neuropharmacol. 40:1-9 (2000) and A. Dogrul et al., Neurosci. Let. 292:115-118 (2000)).


Nociceptive pain has been traditionally managed by administering non-opioid analgesics, such as acetylsalicylic acid, choline magnesium trisalicylate, acetaminophen, ibuprofen, fenoprofen, diflusinal, and naproxen; or opioid analgesics, including morphine, hydromorphone, methadone, levorphanol, fentanyl, oxycodone, and oxymorphone. Id. In addition to the above-listed treatments, neuropathic pain, which can be difficult to treat, has also been treated with anti-epileptics (e.g., gabapentin, carbamazepine, valproic acid, topiramate, phenyloin), NMDA antagonists (e.g., ketamine, dextromethorphan), topical lidocaine (for post-herpetic neuralgia), and tricyclic antidepressants (e.g., fluoxetine, sertraline and amitriptyline).


UI is uncontrollable urination, generally caused by bladder-detrusor-muscle instability. UI affects people of all ages and levels of physical health, both in health care settings and in the community at large. Physiologic bladder contraction results in large part from acetylcholine-induced stimulation of post-ganglionic muscarinic-receptor sites on bladder smooth muscle. Treatments for UI include the administration of drugs having bladder-relaxant properties, which help to control bladder-detrusor-muscle overactivity. For example, anticholinergics such as propantheline bromide and glycopyrrolate, and combinations of smooth-muscle relaxants such as a combination of racemic oxybutynin and dicyclomine or an anticholinergic, have been used to treat UI (See, e.g., A. J. Wein, Urol. Clin. N. Am. 22:557-577 (1995); Levin et al., J. Urol. 128:396-398 (1982); Cooke et al., S. Afr. Med. J. 63:3 (1983); R. K. Mirakhur et al., Anaesthesia 38:1195-1204 (1983)). These drugs are not effective, however, in all patients having uninhibited bladder contractions.


None of the existing commercial drug treatments for UI has achieved complete success in all classes of UI patients, nor has treatment occurred without significant adverse side effects. For example, drowsiness, dry mouth, constipation, blurred vision, headaches, tachycardia, and cardiac arrhythmia, which are related to the anticholinergic activity of traditional anti-UI drugs, can occur frequently and adversely affect patient compliance. Yet despite the prevalence of unwanted anticholinergic effects in many patients, anticholinergic drugs are currently prescribed for patients having UI. The Merck Manual of Medical Information 631-634 (R. Berkow ed., 1997).


Ulcers are sores occurring where the lining of the digestive tract has been eroded by stomach acids or digestive juices. The sores are typically well-defined round or oval lesions primarily occurring in the stomach and duodenum. About 1 in 10 people develop an ulcer. Ulcers develop as a result of an imbalance between acid-secretory factors, also known as “aggressive factors,” such as stomach acid, pepsin, and Helicobacter pylori infection, and local mucosal-protective factors, such as secretion of bicarbonate, mucus, and prostaglandins.


Treatment of ulcers typically involves reducing or inhibiting the aggressive factors. For example, antacids such as aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, and calcium bicarbonate can be used to neutralize stomach acids. Antacids, however, can cause alkalosis, leading to nausea, headache, and weakness. Antacids can also interfere with the absorption of other drugs into the blood stream and cause diarrhea.


H2 antagonists, such as cimetidine, ranitidine, famotidine, and nizatidine, are also used to treat ulcers. H2 antagonists promote ulcer healing by reducing gastric acid and digestive-enzyme secretion elicited by histamine and other H2 agonists in the stomach and duodenum. H2 antagonists, however, can cause breast enlargement and impotence in men, mental changes (especially in the elderly), headache, dizziness, nausea, myalgia, diarrhea, rash, and fever.


H+, K+-ATPase inhibitors such as omeprazole and lansoprazole are also used to treat ulcers. H+, K+-ATPase inhibitors inhibit the production of enzymes used by the stomach to secrete acid. Side effects associated with H+, K+-ATPase inhibitors include nausea, diarrhea, abdominal colic, headache, dizziness, somnolence, skin rashes, and transient elevations of plasma activities of aminotransferases.


Sucraflate is also used to treat ulcers. Sucraflate adheres to epithelial cells and is believed to form a protective coating at the base of an ulcer to promote healing. Sucraflate, however, can cause constipation, dry mouth, and interfere with the absorption of other drugs.


Antibiotics are used when Helicobacter pylori is the underlying cause of the ulcer. Often antibiotic therapy is coupled with the administration of bismuth compounds such as bismuth subsalicylate and colloidal bismuth citrate. The bismuth compounds are believed to enhance secretion of mucous and HCO3, inhibit pepsin activity, and act as an antibacterial against H. pylori. Ingestion of bismuth compounds, however, can lead to elevated plasma concentrations of Bi+3 and can interfere with the absorption of other drugs.


Prostaglandin analogues, such as misoprostal, inhibit secretion of acid and stimulate the secretion of mucous and bicarbonate and are also used to treat ulcers, especially ulcers in patients who require nonsteroidal anti-inflammatory drugs. Effective oral doses of prostaglandin analogues, however, can cause diarrhea and abdominal cramping. In addition, some prostaglandin analogues are abortifacients.


Carbenoxolone, a mineral corticoid, can also be used to treat ulcers. Carbenoxolone appears to alter the composition and quantity of mucous, thereby enhancing the mucosal barrier. Carbenoxolone, however, can lead to Na+ and fluid retention, hypertension, hypokalemia, and impaired glucose tolerance.


Muscarinic cholinergic antagonists such as pirenzapine and telenzapine can also be used to reduce acid secretion and treat ulcers. Side effects of muscarinic cholinergic antagonists include dry mouth, blurred vision, and constipation. The Merck Manual of Medical Information 496-500 (R. Berkow ed., 1997) and Goodman and Gilman's The Pharmacological Basis of Therapeutics 901-915 (J. Hardman and L. Limbird eds., 9th ed. 1996).


Inflammatory-bowel disease (“IBD”) is a chronic disorder in which the bowel becomes inflamed, often causing recurring abdominal cramps and diarrhea. The two types of IBD are Crohn's disease and ulcerative colitis.


Crohn's disease, which can include regional enteritis, granulomatous ileitis, and ileocolitis, is a chronic inflammation of the intestinal wall. Crohn's disease occurs equally in both sexes and is more common in Jews of eastern-European ancestry. Most cases of Crohn's disease begin before age 30 and the majority start between the ages of 14 and 24. The disease typically affects the full thickness of the intestinal wall. Generally the disease affects the lowest portion of the small intestine (ileum) and the large intestine, but can occur in any part of the digestive tract.


Early symptoms of Crohn's disease are chronic diarrhea, crampy abdominal pain, fever, loss of appetite, and weight loss. Complications associated with Crohn's disease include the development of intestinal obstructions, abnormal connecting channels (fistulas), and abscesses. The risk of cancer of the large intestine is increased in people who have Crohn's disease. Often Crohn's disease is associated with other disorders such as gallstones, inadequate absorption of nutrients, amyloidosis, arthritis, episcleritis, aphthous stomatitis, erythema nodosum, pyoderma gangrenosum, ankylosing spondylitis, sacroilitis, uveitis, and primary sclerosing cholangitis. There is no known cure for Crohn's disease.


Cramps and diarrhea, side effects associated with Crohn's disease, can be relieved by anticholinergic drugs, diphenoxylate, loperamide, deodorized opium tincture, or codeine. Generally, the drug is taken orally before a meal.


Broad-spectrum antibiotics are often administered to treat the symptoms of Crohn's disease. The antibiotic metronidazole is often administered when the disease affects the large intestine or causes abscesses and fistulas around the anus. Long-term use of metronidazole, however, can damage nerves, resulting in pins-and-needles sensations in the arms and legs. Sulfasalazine and chemically related drugs can suppress mild inflammation, especially in the large intestine. These drugs, however, are less effective in sudden, severe flare-ups. Corticosteroids, such as prednisone, reduce fever and diarrhea and relieve abdominal pain and tenderness. Long-term corticosteroid therapy, however, invariably results in serious side effects such as high blood-sugar levels, increased risk of infection, osteoporosis, water retention, and fragility of the skin. Drugs such as azathioprine and mercaptourine can compromise the immune system and are often effective for Crohn's disease in patients that do not respond to other drugs. These drugs, however, usually need 3 to 6 months before they produce benefits and can cause serious side effects such as allergy, pancreatitis, and low white-blood-cell count.


When Crohn's disease causes the intestine to be obstructed or when abscesses or fistulas do not heal, surgery can be necessary to remove diseased sections of the intestine. Surgery, however, does not cure the disease, and inflammation tends to recur where the intestine is rejoined. In almost half of the cases a second operation is needed. The Merck Manual of Medical Information 528-530 (R. Berkow ed., 1997).


Ulcerative colitis is a chronic disease in which the large intestine becomes inflamed and ulcerated, leading to episodes of bloody diarrhea, abdominal cramps, and fever. Ulcerative colitis usually begins between ages 15 and 30; however, a small group of people have their first attack between ages 50 and 70. Unlike Crohn's disease, ulcerative colitis never affects the small intestine and does not affect the full thickness of the intestine. The disease usually begins in the rectum and the sigmoid colon and eventually spreads partially or completely throughout the large intestine. The cause of ulcerative colitis is unknown.


Treatment of ulcerative colitis is directed to controlling inflammation, reducing symptoms, and replacing lost fluids and nutrients. Anticholinergic drugs and low doses of diphenoxylate or loperamide are administered for treating mild diarrhea. For more intense diarrhea higher doses of diphenoxylate or loperamide, or deodorized opium tincture or codeine are administered. Sulfasalazine, olsalazine, prednisone, or mesalamine can be used to reduce inflammation. Azathioprine and mercaptopurine have been used to maintain remissions in ulcerative-colitis patients who would otherwise need long-term corticosteroid treatment. In severe cases of ulcerative colitis the patient is hospitalized and given corticosteroids intravenously. People with severe rectal bleeding can require transfusions and intravenous fluids. If toxic colitis develops and treatments fail, surgery to remove the large intestine can be necessary. Non-emergency surgery can be performed if cancer is diagnosed, precancerous lesions are detected, or unremitting chronic disease would otherwise make the person an invalid or dependent on high doses of corticosteroids. Complete removal of the large intestine and rectum permanently cures ulcerative colitis. The Merck Manual of Medical Information 530-532 (R. Berkow ed., 1997) and Goodman and Gilman's The Pharmacological Basis of Therapeutics (J. Hardman and L. Limbird eds., 9th ed. 1996).


Irritable-bowel syndrome (“IBS”) is a disorder of motility of the entire gastrointestinal tract, causing abdominal pain, constipation, and/or diarrhea. IBS affects three-times more women than men. In IBS stimuli such as stress, diet, drugs, hormones, or irritants can cause the gastrointestinal tract to contract abnormally. During an episode of IBS, contractions of the gastrointestinal tract become stronger and more frequent, resulting in the rapid transit of food and feces through the small intestine, often leading to diarrhea. Cramps result from the strong contractions of the large intestine and increased sensitivity of pain receptors in the large intestine.


There are two major types of IBS. The first type, spastic-colon type, is commonly triggered by eating, and usually produces periodic constipation and diarrhea with pain. Mucous often appears in the stool. The pain can come in bouts of continuous dull aching pain or cramps, usually in the lower abdomen. The person suffering from spastic-colon type IBS can also experience bloating, gas, nausea, headache, fatigue, depression, anxiety, and difficulty concentrating. The second type of IBS usually produces painless diarrhea or constipation. The diarrhea can begin suddenly and with extreme urgency. Often the diarrhea occurs soon after a meal and can sometimes occur immediately upon awakening.


Treatment of IBS typically involves modification of an IBS-patient's diet. Often it is recommended that an IBS patient avoid beans, cabbage, sorbitol, and fructose. A low-fat, high-fiber diet can also help some IBS patients. Regular physical activity can also help keep the gastrointestinal tract functioning properly. Drugs such as propantheline that slow the function of the gastrointestinal tract are generally not effective for treating IBS. Antidiarrheal drugs, such as diphenoxylate and loperamide, help with diarrhea. The Merck Manual of Medical Information 525-526 (R. Berkow ed., 1997).


Certain pharmaceutical agents have been administered for treating addiction. U.S. Pat. No. 5,556,838 to Mayer et al. discloses the use of nontoxic NMDA-blocking agents co-administered with an addictive substance to prevent the development of tolerance or withdrawal symptoms. U.S. Pat. No. 5,574,052 to Rose et al. discloses co-administration of an addictive substance with an antagonist to partially block the pharmacological effects of the addictive substance. U.S. Pat. No. 5,075,341 to Mendelson et al. discloses the use of a mixed opiate agonist/antagonist to treat cocaine and opiate addiction. U.S. Pat. No. 5,232,934 to Downs discloses administration of 3-phenoxypyridine to treat addiction. U.S. Pat. Nos. 5,039,680 and 5,198,459 to Imperato et al. disclose using a serotonin antagonist to treat chemical addiction. U.S. Pat. No. 5,556,837 to Nestler et. al. discloses infusing BDNF or NT-4 growth factors to inhibit or reverse neurological adaptive changes that correlate with behavioral changes in an addicted individual. U.S. Pat. No. 5,762,925 to Sagan discloses implanting encapsulated adrenal medullary cells into an animal's central nervous system to inhibit the development of opioid tolerance. U.S. Pat. No. 6,204,284 to Beer et al. discloses racemic (±)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane for use in the prevention or relief of a withdrawal syndrome resulting from addiction to drugs and for the treatment of chemical dependencies.


Without treatment, Parkinson's disease progresses to a rigid akinetic state in which patients are incapable of caring for themselves. Death frequently results from complications of immobility, including aspiration pneumonia or pulmonary embolism. Drugs commonly used for the treatment of Parkinson's disease include carbidopa/levodopa, pergolide, bromocriptine, selegiline, amantadine, and trihexyphenidyl hydrochloride. There remains, however, a need for drugs useful for the treatment of Parkinson's disease and having an improved therapeutic profile.


Currently, benzodiazepines are the most commonly used anti-anxiety agents for generalized anxiety disorder. Benzodiazepines, however, carry the risk of producing impairment of cognition and skilled motor functions, particularly in the elderly, which can result in confusion, delerium, and falls with fractures. Sedatives are also commonly prescribed for treating anxiety. The azapirones, such as buspirone, are also used to treat moderate anxiety. The azapirones, however, are less useful for treating severe anxiety accompanied with panic attacks.


Examples of drugs for treating a seizure and epilepsy include carbamazepine, ethosuximide, gabapentin, lamotrigine, phenobarbital, phenyloin, primidone, valproic acid, trimethadione, benzodiazepines, γ-vinyl GABA, acetazolamide, and felbamate. Anti-seizure drugs, however, can have side effects such as drowsiness; hyperactivity; hallucinations; inability to concentrate; central and peripheral nervous system toxicity, such as nystagmus, ataxia, diplopia, and vertigo; gingival hyperplasia; gastrointestinal disturbances such as nausea, vomiting, epigastric pain, and anorexia; endocrine effects such as inhibition of antidiuretic hormone, hyperglycemia, glycosuria, osteomalacia; and hypersensitivity such as scarlatiniform rash, morbilliform rash, Stevens-Johnson syndrome, systemic lupus erythematosus, and hepatic necrosis; and hematological reactions such as red-cell aplasia, agranulocytosis, thrombocytopenia, aplastic anemia, and megaloblastic anemia. The Merck Manual of Medical Information 345-350 (R. Berkow ed., 1997).


Symptoms of strokes vary depending on what part of the brain is affected. Symptoms include loss or abnormal sensations in an arm or leg or one side of the body, weakness or paralysis of an arm or leg or one side of the body, partial loss of vison or hearing, double vision, dizziness, slurred speech, difficulty in thinking of the appropriate word or saying it, inability to recognize parts of the body, unusual movements, loss of bladder control, imbalance, and falling, and fainting. The symptoms can be permanent and can be associated with coma or stupor. Examples of drugs for treating strokes include anticoagulants such as heparin, drugs that break up clots such as streptokinase or tissue plasminogen activator, and drugs that reduce swelling such as mannitol or corticosteroids. The Merck Manual of Medical Information 352-355 (R. Berkow ed., 1997).


Pruritus is an unpleasant sensation that prompts scratching. Conventionally, pruritus is treated by phototherapy with ultraviolet B or PUVA or with therapeutic agents such as naltrexone, nalmefene, danazol, tricyclics, and antidepressants.


Selective antagonists of the metabotropic glutamate receptor 5 (“mGluR5”) have been shown to exert analgesic activity in in vivo animal models (K. Walker et al., Neuropharmacol. 40:1-9 (2000) and A. Dogrul et al., Neurosci. Let. 292(2): 115-118 (2000)).


Selective antagonists of the mGluR5 receptor have also been shown to exert anxiolytic and anti-depressant activity in in vivo animal models (E. Tatarczynska et al., Brit. J. Pharmacol. 132(7):1423-1430 (2001) and P. J. M. Will et al., Trends in Pharmacological Sci. 22(7):331-37 (2001)).


Selective antagonists of the mGluR5 receptor have also been shown to exert anti-Parkinson activity in vivo (K. J. Ossowska et al., Neuropharmacol. 41(4):413-20 (2001) and P. J. M. Will et al., Trends in Pharmacological Sci. 22(7):331-37 (2001)).


Selective antagonists of the mGluR5 receptor have also been shown to exert anti-dependence activity in vivo (C. Chiamulera et al., Nature Neurosci. 4(9):873-74 (2001)).


U.S. published patent application no. US 2002/0091116 to Zhu et al. describes a class of compounds useful as selective inhibitors of isolated factor Xa or useful when assembled in the prothrombinase complex.


U.S. Pat. No. 5,474,996 to Caille et al. describes a class of pyrimidine derivatives having angiotensin II inhibiting activity.


U.S. Pat. No. 6,063,930 to Dinsmore et al. describes a class of compounds that are useful for inhibiting farnesyl-protein transferase and for the farnesylation of Ras, an oncogene protein.


Citation of any reference in Section 2 of this application is not to be construed as an admission that such reference is prior art to the present application.


3. SUMMARY OF THE INVENTION

The present invention encompasses compounds of formula:




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and pharmaceutically acceptable salts thereof, wherein


Ar1 is




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Ar2 is




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V is N or CH;


X is O or S;


R1 is —H, -halo, —(C1-C4)alkyl, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo);


each R2 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C5-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


R4 is —H or —(C1-C6)alkyl;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each R8 is independently —(C1-C10)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —R7OR7, —R7COR7, —R7C(O)OR7, —R7OC(O)R7, —R7OC(O)OR7, —R7SR7, —R7S(O)R7, —R7S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), —C(OH)(CF3)2, —(C1-C10)alkyl, or -(3- to 7-membered)heterocycle;


each R9 is independently —H, -halo, or —(C1-C6)alkyl;


each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7;


Y1 and Y2 are —CH2— and —CH2—, —O— and —O—, —NH— and —NH—, —S— and —S—, —CH2— and —O—, —CH2— and —NH—, —CH2— and —S—, —O— and —CH2—, —NH— and —CH2—, —S— and —CH2—, —O— and —NH—, —NH— and —O—, —S— and —NH—, or —NH— and —S— respectively; each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


n is an integer ranging from 0 to 3;


p is an integer ranging from 0 to 2;


q is an integer ranging from 0 to 6;


r is an integer ranging from 0 to 5; and


s is an integer ranging from 0 to 4.


The present invention encompasses compounds of formula:




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and pharmaceutically acceptable salts thereof, wherein


Ar1 is




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Ar2 is




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V is N or CH;


R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo);


each R2 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7;


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


n is an integer ranging from 0 to 3;


p is an integer ranging from 0 to 2;


q is an integer ranging from 0 to 6;


r is an integer ranging from 0 to 5; and


s is an integer ranging from 0 to 4.


A Compound of Formula (I) or (IA) or a pharmaceutically acceptable salt thereof (a “Cyclo(hetero)alkenyl Compound”), is useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression (each being a “Condition”) in an animal.


The invention also relates to compositions comprising an effective amount of a Cyclo(hetero)alkenyl Compound and a pharmaceutically acceptable carrier or excipient. The compositions are useful for treating or preventing a Condition in an animal.


The invention further relates to methods for treating a Condition, comprising administering to an animal in need thereof an effective amount of a Cyclo(hetero)alkenyl Compound.


The invention further relates to methods for preventing a Condition, comprising administering to an animal in need thereof an effective amount of a Cyclo(hetero)alkenyl Compound.


The invention still further relates to methods for inhibiting Vanilloid Receptor 1 (“VR1”) function in a cell, comprising contacting a cell capable of expressing VR1 with an effective amount of a Cyclo(hetero)alkenyl Compound.


The invention still further relates to a method for preparing a composition, comprising the step of admixing a Cyclo(hetero)alkenyl Compound and a pharmaceutically acceptable carrier or excipient.


The invention still further relates to a kit comprising a container containing an effective amount of a Cyclo(hetero)alkenyl Compound. The kit may further comprise printed instructions for using the Cyclo(hetero)alkenyl Compound to treat any of the aforementioned Conditions.


The present invention can be understood more fully by reference to the following detailed description and illustrative examples, which are intended to exemplify non-limiting embodiments of the invention.







4. DETAILED DESCRIPTION OF THE INVENTION
4.1 Cyclo(Hetero)Alkenyl Compounds
4.1.1 Cyclo(Hetero)Alkenyl Compounds of Formula (I)

The present invention encompasses Compounds of Formula (I)




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and pharmaceutically acceptable salts thereof, where V, X, Ar1, Ar2, R3, R4, and m are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


In one embodiment, each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —R7OR7, —R7COR7, —R7C(O)OR7, —R7OC(O)R7, —R7OC(O)OR7, —R7SR7, —R7S(O)R7, —R7S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), —C(OH)(CF3)2, —(C1-C10)alkyl, or -(3- to 7-membered)heterocycle.


In another embodiment, R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo).


In another embodiment, Ar2 is




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In another embodiment, Ar1 is




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In another embodiment, Ar2 is




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and Ar1 is




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In another embodiment, each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —C N, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, Ar2 is




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and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, Ar1 is




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and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, Ar2 is




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Ar1 is




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and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, R4 is —H.


In another embodiment, Ar2 is




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and R4 is —H.


In another embodiment, Ar1 is




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and R4 is —H.


In another embodiment, Ar2 is




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Ar1 is




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and R4 is —H.


In another embodiment, R4 is —H and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, Ar2 is




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each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7, and


R4 is —H.


In another embodiment, Ar1 is




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each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7, and


R4 is —H.


In another embodiment, Ar2 is




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Ar1 is




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each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7, and R4 is —H.


In another embodiment, R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); and Ar2 is




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In another embodiment, Ar1 is




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and R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo).


In another embodiment, Ar2 is




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Ar1 is




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and R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo).


In another embodiment, R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, Ar2 is




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each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7; and R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo).


In another embodiment, Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, Ar2 is




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each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7; Ar1 is




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and R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo).


In another embodiment, R is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2 (halo); and R4 is —H.


In another embodiment, Ar2 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); and R4 is —H.


In another embodiment, Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); and R4 is —H.


In another embodiment, Ar2 is




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Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); and R4 is —H.


In another embodiment, R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); R4 is —H; and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, Ar2 is




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each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7; R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); and R4 is —H.


In another embodiment, Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo); each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7, and R4 is —H.


In another embodiment, Ar2 is




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each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7; Ar1 is




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and R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, C(halo)3, —CH(halo)2, or —CH2(halo).


In one embodiment, Ar1 is a pyridyl group.


In another embodiment, Ar1 is a pyrimidyl group


In another embodiment, Ar1 is a pyrazinyl group.


In another embodiment, Ar1 is a pyridazinyl group.


In another embodiment, Ar1 is a thiadiazolyl group.


In another embodiment, Ar1 is




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In another embodiment, Ar1 is




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In another embodiment, Ar1 is




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In another embodiment, V is N.


In another embodiment, V is CH.


In another embodiment, Ar2 is a benzoimidazolyl group.


In another embodiment, Ar2 is a benzothiazolyl group.


In another embodiment, Ar2 is a benzooxazolyl group.


In another embodiment, Ar2 is a 5-benzodioxolyl group, a 5-benzodithiolyl group, a 5-dihydroindenyl group, a 5-dihydrobenzoimidazolyl group, a 6-dihydrobenzofuranyl group, a 5-dihydrobenzofuranyl group, a 6-indolinyl group, a 5-indolinyl group, a 6-dihydrobenzothiopheneyl group, a 5-dihydrobenzothiopheneyl group, a 5-dihydrobenzooxazolyl group, a 6-dihydrobenzooxazolyl group, a 5-dihydrobenzothiazolyl group, or a 6-dihydrobenzothiazolyl group.


In another embodiment, Ar2 is a 5-benzodioxolyl group, a 5-benzodithiolyl group, a 5-dihydroindenyl group, a 5-dihydrobenzoimidazolyl group, a 6-dihydrobenzofuranyl group, a 5-dihydrobenzofuranyl group, a 6-indolinyl group, a 5-indolinyl group, a 6-dihydrobenzothiopheneyl group, or a 5-dihydrobenzothiopheneyl group.


In another embodiment, Ar2 is a 5-dihydroindenyl group, a 5-dihydrobenzoimidazolyl group, a 5-benzodioxolyl group, or a 5-benzodithiolyl group.


In another embodiment, Ar2 is a 5-benzodioxolyl group or a 5-benzodithiolyl group.


In another embodiment, Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar2 is a 5-benzodithiolyl group.


In another embodiment, Ar2 is




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In another embodiment, Ar2 is




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In another embodiment, Ar2 is




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In another embodiment, Ar2 is




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In another embodiment, Ar2 is




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In another embodiment, Ar2 is




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In another embodiment, p or n is 0.


In another embodiment, p or n is 1.


In another embodiment, m is 0.


In another embodiment, m is 0 and V is N.


In another embodiment, m is 0 and V is CH.


In another embodiment, m is 1.


In another embodiment, m is 1 and V is N.


In another embodiment, m is 1 and V is CH.


In another embodiment, Ar2 is




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and s is 0.


In another embodiment, Ar2 is




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and s is 1.


In another embodiment, Ar2 is




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and q is 0.


In another embodiment, Ar2 is




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and q is 1.


In another embodiment, Ar2 is




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and r is 0.


In another embodiment, Ar2 is




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and r is 0.


In another embodiment, Ar2 is a benzothiazolyl group and s is 0.


In another embodiment, Ar2 is a benzoimidazolyl group and s is 0.


In another embodiment, Ar2 is a benzooxazolyl group and s is 0.


In another embodiment, Ar2 is a benzothiazolyl group and s is 1.


In another embodiment, Ar2 is a benzoimidazolyl group and s is 1.


In another embodiment, Ar2 is a benzooxazolyl group and s is 1.


In another embodiment, Ar2 is a 5-benzodioxolyl group and each R9 is —H.


In another embodiment, Ar2 is a 5-benzodioxolyl group and each R9 is —F.


In another embodiment, R1 is —H.


In another embodiment, R2 is -halo.


In another embodiment, R1 is —(C1-C4)alkyl.


In another embodiment, R1 is —CH3 or —CH2CH3.


In another embodiment, R1 is —CH2CH3.


In another embodiment, R1 is —CH3.


In another embodiment, R1 is —NO2.


In another embodiment, R1 is —CN.


In another embodiment, R1 is —OH.


In another embodiment, R1 is —OCH3.


In another embodiment, R1 is —NH2.


In another embodiment, R1 is —C(halo)3.


In another embodiment, R1 is —CH(halo)2.


In another embodiment, R1 is —CH2(halo).


In another embodiment, n or p is 1 and R2 is -halo, —CN, —OH, —NO2, or —NH2.


In another embodiment, n or p is 1 and R2 is —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.


In another embodiment, n or p is 1 and R2 is -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups.


In another embodiment, m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring, and R3 is -halo, —CN, —OH, —NO2, or —NH2;


In another embodiment, m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring, and R3 is —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.


In another embodiment, m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring, and R3 is -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups.


In another embodiment, m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring, and R3 is —CH3.


In another embodiment, R4 is —H.


In another embodiment, R4 is —(C1-C6)alkyl.


In another embodiment, R4 is ethyl.


In another embodiment, R4 is methyl.


In another embodiment, R4 is —H or methyl.


In another embodiment, each R8 is independently —(C1-C10)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -(3- to 7-membered)heterocycle, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —R7C(O)OR7, —OC(O)R7, —R7OC(O)R7, —OC(O)OR7, —R7OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.


In another embodiment, each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, or —C(halo)2C(halo)3.


In another embodiment, Ar2 is a benzothiazolyl group, benzoimidazolyl group, or benzooxazolyl group and each R8 is independently —H, halo, —(C1-C6)alkyl, —O(C1-C6)alkyl, —C(halo)3, —CH(halo)2, or —CH2(halo).


In another embodiment, Ar2 is




embedded image



and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), or —C(OH)(CF3)2.


In another embodiment, Ar2 is




embedded image



and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), or —C(OH)(CF3)2.


In another embodiment, Ar2 is




embedded image



and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), or —C(OH)(CF3)2.


In another embodiment, Ar2 is




embedded image



and each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7.


In another embodiment, Ar1 is a pyridyl group; V is N; m is 0, and Ar2 is a benzothiazolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; R8 s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl rig.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Art is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; and s is 1. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; —F —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group, V is CH; m is 0, and Ar2 is a benzothiazolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; R8 s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F—Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; and s is 1. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment the R3 group in attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzothiazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group, V is N; m is 0, and Ar2 is a benzoimidazolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; R8 s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; v is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; and s is 1. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In other embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Art is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group, V is CH; m is 0, and Ar2 is a benzoimidazolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; R8 s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F—Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; and s is 1. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzoimidazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group, V is N; m is 0, and Ar2 is a benzooxazolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; R8 s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Art is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; and s is 1. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the 3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group, V is CH; m is 0, and Ar2 is a benzooxazolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; R8 s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Art is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group s is 1; and R8 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is −1; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; and s is 1. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the . . . cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a benzooxazolyl group; s is 1; and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, V is N, Ar1 is a pyridyl group, m is 0, and Ar2 is




embedded image


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is chloro. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3, Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3, Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



r is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, V is CH, Ar1 is a pyridyl group, m is 0, and Ar2 is




embedded image


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



and r is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is (R8)r




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is chloro. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Art is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



and r is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; —R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Art is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



r is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is —OCH2CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



r is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 4-position of the phenyl ring.


In another embodiment, V is N, Ar1 is a pyridyl group, m is 0, and Ar2 is




embedded image


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0, R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is chloro. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (P) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3, Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R1) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3, Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, V is CH, Ar1 is a pyridyl group, m is 0, and Ar2 is




embedded image


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



and s is 0.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is chloro. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is




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s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is




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s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



and s is 0. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is




embedded image



s is 1; and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is —CH2CF3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is




embedded image



s is 1 and R8 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring. In another embodiment, R8 is at the 5-position of the Ar2 pyridyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; m is 0, and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl;


Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br;


Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F, —Cl —Br, or —I; Ar2 is a 5-benzodioxolyl group; R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Art is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar(is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is N; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group, V is CH; m is 0, and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group and each R9 is —Cl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl, —F, —Br, or —I, Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; and Ar2 is a 5-benzodioxolyl group.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —I.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 0; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; and Ar2 is a 5-benzodioxolyl group. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -halo. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Br. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —F. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is CH3; R1 is —Cl, —F —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —Cl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl, —F, —Br, or —I, Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —I. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is —CH3. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -ethyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -isopropyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F, —Cl, —Br, or —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —F; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Cl; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —Br; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —I; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CH3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In another embodiment, Ar1 is a pyridyl group; V is CH; n is 0; m is 1; R3 is —CH3; R1 is —CF3; Ar2 is a 5-benzodioxolyl group; and each R9 is -tert-butyl. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the R3 group is attached to the 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring and the carbon atom to which the R3 group is attached has the (S) configuration. In yet another embodiment, the R3 group is attached to the 2-position of the cyclo(hetero)alkenyl ring.


In the Cyclo(hetero)alkenyl Compounds that have an R3 group, the R3 group can be attached to the carbon at the 2-, 3-, 5- or 6-position of the cyclo(hetero)alkenyl ring. In one embodiment, the R3 group is attached to the carbon at the 3-position of the cyclo(hetero)alkenyl ring. In another embodiment, the R3 group is attached to the carbon at the 5-position of the cyclo(hetero)alkenyl ring. In another embodiment, the R3 group is attached to the carbon at the 6-position of the cyclo(hetero)alkenyl ring. In another embodiment, the R3 group is attached to the carbon at the 2-position of the


In one embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group; the carbon atom to which the R3 group is attached is at the 3-, 5- or 6-position of the tetrahydropiperidine ring; and the carbon atom to which the R3 group is attached has the (R) configuration. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group; the carbon atom to which the R3 group is attached is at the 3-, 5- or 6-position of the tetrahydropiperidine ring; and the carbon atom to which the R3 group is attached has the (S) configuration.


In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, and the carbon to which the R3 group is attached is in the (R) configuration. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —(C1-C4)alkyl unsubstituted or substituted with one or more halo groups. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CH3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CF3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CH2CH3.


In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, and the carbon to which the R3 group is attached is in the (R) configuration. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —(C1-C4)alkyl unsubstituted or substituted with one or more halo groups. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CH3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CF3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CH2CH3.


In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, and the carbon to which the R3 group is attached is in the (R) configuration. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydrorpiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —(C1-C4)alkyl unsubstituted or substituted with one or more halo groups. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CH3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (R) configuration, and R3 is —CF3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring. The R3 group is in the (R) configuration, and R3 is —CH2CH3.


In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, and the carbon to which the R3 group is attached is in the (S) configuration. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —(C1-C4)alkyl unsubstituted or substituted with one or more halo groups. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CH3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CF3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon that is at the 3-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CH2CH3.


In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, and the carbon to which the R3 group is attached is in the (S) configuration. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —(C1-C4)alkyl unsubstituted or substituted with one or more halo groups. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CH3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CF3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 6-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CH2CH3.


In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, and the carbon to which the R3 group is attached is in the (S) configuration. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —(C1-C4)alkyl unsubstituted or substituted with one or more halo groups. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CH3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, the carbon to which the R3 group is attached is in the (S) configuration, and R3 is —CF3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 5-position of the tetrahydropiperidine ring, the carbon atom to which the R3 group is attached is in the (S) configuration, and R3 is —CH2CH3.


In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 2-position of the cyclo(hetero)alkenyl ring and R3 is —(C1-C4) alkyl unsubstituted or substituted with one or more halo groups. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 2-position of the cyclo(hetero)alkenyl ring and R3 is —CH3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 2-position of the cyclo(hetero)alkenyl ring and R3 is —CF3. In another embodiment, the Cyclo(hetero)alkenyl Compound has an R3 group, the R3 group is attached to the carbon atom at the 2-position of the cyclo(hetero)alkenyl ring and R3 is —CH2CH3.


4.1.2 Cyclo(Hetero)Alkenyl Compounds of Formula (IA)

The present invention encompasses Compounds of Formula (IA)




embedded image



and pharmaceutically acceptable salts thereof, where V, Ar1, Ar2, R3, and m are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (IA).


Illustrative Cyclo(hetero)alkenyl Compounds are listed below in Tables 1-27.


For the chemical structure depicted, e.g., at the head of each of Tables 1, 3, 5, 7, 9, 13-19, 21, 22, 24, 25 and 27, a is independently 0 or 1. When a=0, the group at the “a” position is —H. When a=1, the group at the “a” position (R8a) is other than —H, i.e., is R8.


For the chemical structure depicted, e.g., at the head of each of Tables 2, 4, 6, 8, 10, 20, 23 and 26, a is independently 0 or 1. When a=0, the group at the “a” position is —H. When a=1, the group at the “a” position ((R8)a) is other than —H, i.e., is R8.


For the chemical structure depicted, e.g., at the head of each of Tables 2, 4, 6, 8, 10, 20, 23 and 26, b is independently 0 or 1. When b=0, the group at the “b” position is —H. When b=1, the group at the “b” position ((R8)b) is other than —H, i.e., is R8.










TABLE 1








(Ia)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






A01 (a and b)
—H
—H



A02 (a and b)
—H
-tert-butyl



A03 (a and b)
—H
-iso-butyl



A04 (a and b)
—H
-sec-butyl



A05 (a and b)
—H
-iso-propyl



A06 (a and b)
—H
-n-propyl



A07 (a and b)
—H
-cyclohexyl



A08 (a and b)
—H
-tert-butoxy



A09 (a and b)
—H
-isopropoxy



A10 (a and b)
—H
—CF3



A11 (a and b)
—H
—CH2CF3



A12 (a and b)
—H
—OCF3



A13 (a and b)
—H
—Cl



A14 (a and b)
—H
—Br



A15 (a and b)
—H
—I



A16 (a and b)
—H
-n-butyl



A17 (a and b)
—H
—CH3



A18 (a and b)
—H
—SCF3



A19 (a and b)
—H
—N(CH2CH3)2



A20 (a and b)
—H
—OCF2CHF2



A21 (a and b)
—H
—C(OH)(CF3)2



A22 (a and b)
—H
-(1,1-dimethyl-pentyl)



A23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



A24 (a and b)
—H
—N-piperidinyl



A25 (a and b)
—Cl
—H



A26 (a and b)
—Cl
-tert-butyl



A27 (a and b)
—Cl
-iso-butyl



A28 (a and b)
—Cl
-sec-butyl



A29 (a and b)
—Cl
-iso-propyl



A30 (a and b)
—Cl
-n-propyl



A31 (a and b)
—Cl
-cyclohexyl



A32 (a and b)
—Cl
-tert-butoxy



A33 (a and b)
—Cl
-isopropoxy



A34 (a and b)
—Cl
—CF3



A35 (a and b)
—Cl
—CH2CF3



A36 (a and b)
—Cl
—OCF3



A37 (a and b)
—Cl
—Cl



A38 (a and b)
—Cl
—Br



A39 (a and b)
—Cl
—I



A40 (a and b)
—Cl
-n-butyl



A41 (a and b)
—Cl
—CH3



A42 (a and b)
—Cl
—SCF3



A43 (a and b)
—Cl
—N(CH2CH3)2



A44 (a and b)
—Cl
—OCF2CHF2



A45 (a and b)
—Cl
—C(OH)(CF3)2



A46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



A47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



A48 (a and b)
—Cl
—N-piperidinyl



A49 (a and b)
—F
—H



A50 (a and b)
—F
-tert-butyl



A51 (a and b)
—F
-iso-butyl



A52 (a and b)
—F
-sec-butyl



A53 (a and b)
—F
-iso-propyl



A54 (a and b)
—F
-n-propyl



A55 (a and b)
—F
-cyclohexyl



A56 (a and b)
—F
-tert-butoxy



A57 (a and b)
—F
-isopropoxy



A58 (a and b)
—F
—CF3



A59 (a and b)
—F
—CH2CF3



A60 (a and b)
—F
—OCF3



A61 (a and b)
—F
—Cl



A62 (a and b)
—F
—Br



A63 (a and b)
—F
—I



A64 (a and b)
—F
-n-butyl



A65 (a and b)
—F
—CH3



A66 (a and b)
—F
—SCF3



A67 (a and b)
—F
—N(CH2CH3)2



A68 (a and b)
—F
—OCF2CHF2



A69 (a and b)
—F
—C(OH)(CF3)2



A70 (a and b)
—F
-(1,1-dimethyl-pentyl)



A71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



A72 (a and b)
—F
—N-piperidinyl



A73 (a and b)
—CH3
—H



A74 (a and b)
—CH3
-iso-butyl



A75 (a and b)
—CH3
-tert-butyl



A76 (a and b)
—CH3
-sec-butyl



A77 (a and b)
—CH3
-iso-propyl



A78 (a and b)
—CH3
-n-propyl



A79 (a and b)
—CH3
-cyclohexyl



A80 (a and b)
—CH3
-tert-butoxy



A81 (a and b)
—CH3
-isopropoxy



A82 (a and b)
—CH3
—CF3



A83 (a and b)
—CH3
—CH2CF3



A84 (a and b)
—CH3
—OCF3



A85 (a and b)
—CH3
—Cl



A86 (a and b)
—CH3
—Br



A87 (a and b)
—CH3
—I



A88 (a and b)
—CH3
-n-butyl



A89 (a and b)
—CH3
—CH3



A90 (a and b)
—CH3
—SCF3



A91 (a and b)
—CH3
—N(CH2CH3)2



A92 (a and b)
—CH3
—OCF2CHF2



A93 (a and b)
—CH3
—C(OH)(CF3)2



A94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



A95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



A96 (a and b)
—CH3
—N-piperidinyl



A97 (a and b)
—CF3
—H



A98 (a and b)
—CF3
-tert-butyl



A99 (a and b)
—CF3
-iso-butyl



A100 (a and b)
—CF3
-sec-butyl



A101 (a and b)
—CF3
-iso-propyl



A102 (a and b)
—CF3
-n-propyl



A103 (a and b)
—CF3
-cyclohexyl



A104 (a and b)
—CF3
-tert-butoxy



A105 (a and b)
—CF3
-isopropoxy



A106 (a and b)
—CF3
—CF3



A107 (a and b)
—CF3
—CH2CF3



A108 (a and b)
—CF3
—OCF3



A109 (a and b)
—CF3
—Cl



A110 (a and b)
—CF3
—Br



A111 (a and b)
—CF3
—I



A112 (a and b)
—CF3
-n-butyl



A113 (a and b)
—CF3
—CH3



A114 (a and b)
—CF3
—SCF3



A115 (a and b)
—CF3
—N(CH2CH3)2



A116 (a and b)
—CF3
—OCF2CHF2



A117 (a and b)
—CF3
—C(OH)(CF3)2



A118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



A119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



A120 (a and b)
—CF3
—N-piperidinyl



A121 (a and b)
—CHF2
-tert-butyl



A122 (a and b)
—CHF2
—H



A123 (a and b)
—CHF2
-iso-butyl



A124 (a and b)
—CHF2
-sec-butyl



A125 (a and b)
—CHF2
-iso-propyl



A126 (a and b)
—CHF2
-n-propyl



A127 (a and b)
—CHF2
-cyclohexyl



A128 (a and b)
—CHF2
-tert-butoxy



A129 (a and b)
—CHF2
-isopropoxy



A130 (a and b)
—CHF2
—CF3



A131 (a and b)
—CHF2
—CH2CF3



A132 (a and b)
—CHF2
—OCF3



A133 (a and b)
—CHF2
—Cl



A134 (a and b)
—CHF2
—Br



A135 (a and b)
—CHF2
—I



A136 (a and b)
—CHF2
-n-butyl



A137 (a and b)
—CHF2
—CH3



A138 (a and b)
—CHF2
—SCF3



A139 (a and b)
—CHF2
—N(CH2CH3)2



A140 (a and b)
—CHF2
—OCF2CHF2



A141 (a and b)
—CHF2
—C(OH)(CF3)2



A142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



A143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



A144 (a and b)
—CHF2
—N-piperidinyl



A145 (a and b)
—OH
—H



A146 (a and b)
—OH
-tert-butyl



A147 (a and b)
—OH
-iso-butyl



A148 (a and b)
—OH
-sec-butyl



A149 (a and b)
—OH
-iso-propyl



A150 (a and b)
—OH
-n-propyl



A151 (a and b)
—OH
-cyclohexyl



A152 (a and b)
—OH
-tert-butoxy



A153 (a and b)
—OH
-isopropoxy



A154 (a and b)
—OH
—CF3



A155 (a and b)
—OH
—CH2CF3



A156 (a and b)
—OH
—OCF3



A157 (a and b)
—OH
—Cl



A158 (a and b)
—OH
—Br



A159 (a and b)
—OH
—I



A160 (a and b)
—OH
-n-butyl



A161 (a and b)
—OH
—CH3



A162 (a and b)
—OH
—SCF3



A163 (a and b)
—OH
—N(CH2CH3)2



A164 (a and b)
—OH
—OCF2CHF2



A165 (a and b)
—OH
—C(OH)(CF3)2



A166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



A167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



A168 (a and b)
—OH
—N-piperidinyl



A169 (a and b)
—NO2
—H



A170 (a and b)
—NO2
-tert-butyl



A171 (a and b)
—NO2
-iso-butyl



A172 (a and b)
—NO2
-sec-butyl



A173 (a and b)
—NO2
-iso-propyl



A174 (a and b)
—NO2
-n-propyl



A175 (a and b)
—NO2
-cyclohexyl



A176 (a and b)
—NO2
-tert-butoxy



A177 (a and b)
—NO2
-isopropoxy



A178 (a and b)
—NO2
—CF3



A179 (a and b)
—NO2
—CH2CF3



A180 (a and b)
—NO2
—OCF3



A181 (a and b)
—NO2
—Cl



A182 (a and b)
—NO2
—Br



A183 (a and b)
—NO2
—I



A184 (a and b)
—NO2
-n-butyl



A185 (a and b)
—NO2
—CH3



A186 (a and b)
—NO2
—SCF3



A187 (a and b)
—NO2
—N(CH2CH3)2



A188 (a and b)
—NO2
—OCF2CHF2



A189 (a and b)
—NO2
—C(OH)(CF3)2



A190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



A191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



A192 (a and b)
—NO2
—N-piperidinyl



A193 (a and b)
—CN
—H



A194 (a and b)
—CN
-tert-butyl



A195 (a and b)
—CN
-iso-butyl



A196 (a and b)
—CN
-sec-butyl



A197 (a and b)
—CN
-iso-propyl



A198 (a and b)
—CN
-n-propyl



A199 (a and b)
—CN
-cyclohexyl



A200 (a and b)
—CN
-tert-butoxy



A201 (a and b)
—CN
-isopropoxy



A202 (a and b)
—CN
—CF3



A203 (a and b)
—CN
—CH2CF3



A204 (a and b)
—CN
—OCF3



A205 (a and b)
—CN
—Cl



A206 (a and b)
—CN
—Br



A207 (a and b)
—CN
—I



A208 (a and b)
—CN
-n-butyl



A209 (a and b)
—CN
—CH3



A210 (a and b)
—CN
—SCF3



A211 (a and b)
—CN
—N(CH2CH3)2



A212 (a and b)
—CN
—OCF2CHF2



A213 (a and b)
—CN
—C(OH)(CF3)2



A214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



A215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



A216 (a and b)
—CN
—N-piperidinyl



A217 (a and b)
—Br
—H



A218 (a and b)
—Br
-tert-butyl



A219 (a and b)
—Br
-iso-butyl



A220 (a and b)
—Br
-sec-butyl



A221 (a and b)
—Br
-iso-propyl



A222 (a and b)
—Br
-n-propyl



A223 (a and b)
—Br
-cyclohexyl



A224 (a and b)
—Br
-tert-butoxy



A225 (a and b)
—Br
-isopropoxy



A226 (a and b)
—Br
—CF3



A227 (a and b)
—Br
—CH2CF3



A228 (a and b)
—Br
—OCF3



A229 (a and b)
—Br
—Cl



A230 (a and b)
—Br
—Br



A231 (a and b)
—Br
—I



A232 (a and b)
—Br
-n-butyl



A233 (a and b)
—Br
—CH3



A234 (a and b)
—Br
—SCF3



A235 (a and b)
—Br
—N(CH2CH3)2



A236 (a and b)
—Br
—OCF2CHF2



A237 (a and b)
—Br
—C(OH)(CF3)2



A238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



A239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



A240 (a and b)
—Br
—N-piperidinyl



A241 (a and b)
—I
-tert-butyl



A242 (a and b)
—I
—H



A243 (a and b)
—I
-iso-butyl



A244 (a and b)
—I
-sec-butyl



A245 (a and b)
—I
-iso-propyl



A246 (a and b)
—I
-n-propyl



A247 (a and b)
—I
-cyclohexyl



A248 (a and b)
—I
-tert-butoxy



A249 (a and b)
—I
-isopropoxy



A250 (a and b)
—I
—CF3



A251 (a and b)
—I
—CH2CF3



A252 (a and b)
—I
—OCF3



A253 (a and b)
—I
—Cl



A254 (a and b)
—I
—Br



A255 (a and b)
—I
—I



A256 (a and b)
—I
-n-butyl



A257 (a and b)
—I
—CH3



A258 (a and b)
—I
—SCF3



A259 (a and b)
—I
—N(CH2CH3)2



A260 (a and b)
—I
—OCF2CHF2



A261 (a and b)
—I
—C(OH)(CF3)2



A262 (a and b)
—I
-(1,1-dimethyl-pentyl)



A263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



A264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 2








(Ib)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
Y
R1
(R8)a
(R8)b





B1 (a and b)
S
—H
—Cl
—H


B2 (a and b)
S
—H
—Br
—H


B3 (a and b)
S
—H
—F
—H


B4 (a and b)
S
—H
—CH3
—H


B5 (a and b)
S
—H
—CF3
—H


B6 (a and b)
S
—H
—OCH3
—H


B7 (a and b)
S
—H
—OCH2CH3
—H


B8 (a and b)
S
—H
—OCF3
—H


B9 (a and b)
S
—H
-tert-butyl
—H


B10 (a and b)
S
—H
-iso-propyl
—H


B11 (a and b)
S
—H
—CH3
—CH3


B12 (a and b)
S
—H
—H
—H


B13 (a and b)
S
—H
—H
—Cl


B14 (a and b)
S
—H
—H
—Br


B15 (a and b)
S
—H
—H
—F


B16 (a and b)
S
—H
—H
—CH3


B17 (a and b)
S
—H
—H
—CF3


B18 (a and b)
S
—H
—H
—OCH3


B19 (a and b)
S
—H
—H
—OCH2CH3


B20 (a and b)
S
—H
—H
—OCF3


B21 (a and b)
S
—H
—H
-tert-butyl


B22 (a and b)
S
—H
—H
-iso-propyl


B23 (a and b)
S
—Cl
—Cl
—H


B24 (a and b)
S
—Cl
—Br
—H


B25 (a and b)
S
—Cl
—F
—H


B26 (a and b)
S
—Cl
—CH3
—H


B27 (a and b)
S
—Cl
—CF3
—H


B28 (a and b)
S
—Cl
—OCH3
—H


B29 (a and b)
S
—Cl
—OCH2CH3
—H


B30 (a and b)
S
—Cl
—OCF3
—H


B31 (a and b)
S
—Cl
-tert-butyl
—H


B32 (a and b)
S
—Cl
-iso-propyl
—H


B33 (a and b)
S
—Cl
—CH3
—CH3


B34 (a and b)
S
—Cl
—H
—H


B35 (a and b)
S
—Cl
—H
—Cl


B36 (a and b)
S
—Cl
—H
—Br


B37 (a and b)
S
—Cl
—H
—F


B38 (a and b)
S
—Cl
—H
—CH3


B39 (a and b)
S
—Cl
—H
—CF3


B40 (a and b)
S
—Cl
—H
—OCH3


B41 (a and b)
S
—Cl
—H
—OCH2CH3


B42 (a and b)
S
—Cl
—H
—OCF3


B43 (a and b)
S
—Cl
—H
-tert-butyl


B44 (a and b)
S
—Cl
—H
-iso-propyl


B45 (a and b)
S
—Cl
—H
—OCF3


B46 (a and b)
S
—Cl
—H
-tert-butyl


B47 (a and b)
S
—Cl
—H
-iso-propyl


B48 (a and b)
S
—CH3
—Cl
—H


B49 (a and b)
S
—CH3
—Br
—H


B50 (a and b)
S
—CH3
—F
—H


B51 (a and b)
S
—CH3
—CH3
—H


B52 (a and b)
S
—CH3
—CF3
—H


B53 (a and b)
S
—CH3
—OCH3
—H


B54 (a and b)
S
—CH3
—OCH2CH3
—H


B55 (a and b)
S
—CH3
—OCF3
—H


B56 (a and b)
S
—CH3
-tert-butyl
—H


B57 (a and b)
S
—CH3
-iso-propyl
—H


B58 (a and b)
S
—CH3
—CH3
—CH3


B59 (a and b)
S
—CH3
—H
—H


B60 (a and b)
S
—CH3
—H
—Cl


B61 (a and b)
S
—CH3
—H
—Br


B62 (a and b)
S
—CH3
—H
—F


B63 (a and b)
S
—CH3
—H
—CH3


B64 (a and b)
S
—CH3
—H
—CF3


B65 (a and b)
S
—CH3
—H
—OCH3


B66 (a and b)
S
—CH3
—H
—OCH2CH3


B67 (a and b)
S
—CH3
—H
—OCF3


B68 (a and b)
S
—CH3
—H
-tert-butyl


B69 (a and b)
S
—CH3
—H
-iso-propyl


B70 (a and b)
S
—CF3
—Cl
—H


B71 (a and b)
S
—CF3
—Br
—H


B72 (a and b)
S
—CF3
—F
—H


B73 (a and b)
S
—CF3
—CH3
—H


B74 (a and b)
S
—CF3
—CF3
—H


B75 (a and b)
S
—CF3
—OCH3
—H


B76 (a and b)
S
—CF3
—OCH2CH3
—H


B77 (a and b)
S
—CF3
—OCF3
—H


B78 (a and b)
S
—CF3
-tert-butyl
—H


B79 (a and b)
S
—CF3
-iso-propyl
—H


B80 (a and b)
S
—CF3
—CH3
—CH3


B81 (a and b)
S
—CF3
—H
—H


B82 (a and b)
S
—CF3
—H
—Cl


B83 (a and b)
S
—CF3
—H
—Br


B84 (a and b)
S
—CF3
—H
—F


B85 (a and b)
S
—CF3
—H
—CH3


B86 (a and b)
S
—CF3
—H
—CF3


B87 (a and b)
S
—CF3
—H
—OCH3


B88 (a and b)
S
—CF3
—H
—OCH2CH3


B89 (a and b)
S
—CF3
—H
—OCF3


B90 (a and b)
S
—CF3
—H
-tert-butyl


B91 (a and b)
S
—CF3
—H
-iso-propyl


B92 (a and b)
S
—CHF2
—Cl
—H


B93 (a and b)
S
—CHF2
—Br
—H


B94 (a and b)
S
—CHF2
—F
—H


B95 (a and b)
S
—CHF2
—CH3
—H


B96 (a and b)
S
—CHF2
—CF3
—H


B97 (a and b)
S
—CHF2
—OCH3
—H


B98 (a and b)
S
—CHF2
—OCH2CH3
—H


B99 (a and b)
S
—CHF2
—OCF3
—H


B100 (a and b)
S
—CHF2
-tert-butyl
—H


B101 (a and b)
S
—CHF2
-iso-propyl
—H


B102 (a and b)
S
—CHF2
—CH3
—CH3


B103 (a and b)
S
—CHF2
—H
—H


B104 (a and b)
S
—CHF2
—H
—Cl


B105 (a and b)
S
—CHF2
—H
—Br


B106 (a and b)
S
—CHF2
—H
—F


B107 (a and b)
S
—CHF2
—H
—CH3


B108 (a and b)
S
—CHF2
—H
—CF3


B109 (a and b)
S
—CHF2
—H
—OCH3


B110 (a and b)
S
—CHF2
—H
—OCH2CH3


B111 (a and b)
S
—CHF2
—H
—OCF3


B112 (a and b)
S
—CHF2
—H
-tert-butyl


B113 (a and b)
S
—CHF2
—H
-iso-propyl


B114 (a and b)
S
—OH
—Cl
—H


B115 (a and b)
S
—OH
—Br
—H


B116 (a and b)
S
—OH
—F
—H


B117 (a and b)
S
—OH
—CH3
—H


B118 (a and b)
S
—OH
—CF3
—H


B119 (a and b)
S
—OH
—OCH3
—H


B120 (a and b)
S
—OH
—OCH2CH3
—H


B121 (a and b)
S
—OH
—OCF3
—H


B122 (a and b)
S
—OH
-tert-butyl
—H


B123 (a and b)
S
—OH
-iso-propyl
—H


B124 (a and b)
S
—OH
—CH3
—CH3


B125 (a and b)
S
—OH
—H
—H


B126 (a and b)
S
—OH
—H
—Cl


B127 (a and b)
S
—OH
—H
—Br


B128 (a and b)
S
—OH
—H
—F


B129 (a and b)
S
—OH
—H
—CH3


B130 (a and b)
S
—OH
—H
—CF3


B131 (a and b)
S
—OH
—H
—OCH3


B132 (a and b)
S
—OH
—H
—OCH2CH3


B133 (a and b)
S
—OH
—H
—OCF3


B134 (a and b)
S
—OH
—H
-tert-butyl


B135 (a and b)
S
—OH
—H
-iso-propyl


B136 (a and b)
S
—NO2
—Cl
—H


B137 (a and b)
S
—NO2
—Br
—H


B138 (a and b)
S
—NO2
—F
—H


B139 (a and b)
S
—NO2
—CH3
—H


B140 (a and b)
S
—NO2
—CF3
—H


B141 (a and b)
S
—NO2
—OCH3
—H


B142 (a and b)
S
—NO2
—OCH2CH3
—H


B143 (a and b)
S
—NO2
—OCF3
—H


B144 (a and b)
S
—NO2
-tert-butyl
—H


B145 (a and b)
S
—NO2
-iso-propyl
—H


B146 (a and b)
S
—NO2
—CH3
—CH3


B147 (a and b)
S
—NO2
—H
—H


B148 (a and b)
S
—NO2
—H
—Cl


B149 (a and b)
S
—NO2
—H
—Br


B150 (a and b)
S
—NO2
—H
—F


B151 (a and b)
S
—NO2
—H
—CH3


B152 (a and b)
S
—NO2
—H
—CF3


B153 (a and b)
S
—NO2
—H
—OCH3


B154 (a and b)
S
—NO2
—H
—OCH2CH3


B155 (a and b)
S
—NO2
—H
—OCF3


B156 (a and b)
S
—NO2
—H
-tert-butyl


B157 (a and b)
S
—NO2
—H
-iso-propyl


B158 (a and b)
S
—CN
—Br
—H


B159 (a and b)
S
—CN
—Cl
—H


B160 (a and b)
S
—CN
—F
—H


B161 (a and b)
S
—CN
—CH3
—H


B162 (a and b)
S
—CN
—CF3
—H


B163 (a and b)
S
—CN
—OCH3
—H


B164 (a and b)
S
—CN
—OCH2CH3
—H


B165 (a and b)
S
—CN
—OCF3
—H


B166 (a and b)
S
—CN
-tert-butyl
—H


B167 (a and b)
S
—CN
-iso-propyl
—H


B168 (a and b)
S
—CN
—CH3
—CH3


B169 (a and b)
S
—CN
—H
—H


B170 (a and b)
S
—CN
—H
—Cl


B171 (a and b)
S
—CN
—H
—Br


B172 (a and b)
S
—CN
—H
—F


B173 (a and b)
S
—CN
—H
—CH3


B174 (a and b)
S
—CN
—H
—CF3


B175 (a and b)
S
—CN
—H
—OCH3


B176 (a and b)
S
—CN
—H
—OCH2CH3


B177 (a and b)
S
—CN
—H
—OCF3


B178 (a and b)
S
—CN
—H
-tert-butyl


B179 (a and b)
S
—CN
—H
-iso-propyl


B180 (a and b)
S
—Br
—Br
—H


B181 (a and b)
S
—Br
—Cl
—H


B182 (a and b)
S
—Br
—F
—H


B183 (a and b)
S
—Br
—CH3
—H


B184 (a and b)
S
—Br
—CF3
—H


B185 (a and b)
S
—Br
—OCH3
—H


B186 (a and b)
S
—Br
—OCH2CH3
—H


B187 (a and b)
S
—Br
—OCF3
—H


B188 (a and b)
S
—Br
-tert-butyl
—H


B189 (a and b)
S
—Br
-iso-propyl
—H


B190 (a and b)
S
—Br
—CH3
—CH3


B191 (a and b)
S
—Br
—H
—H


B192 (a and b)
S
—Br
—H
—Cl


B193 (a and b)
S
—Br
—H
—Br


B194 (a and b)
S
—Br
—H
—F


B195 (a and b)
S
—Br
—H
—CH3


B196 (a and b)
S
—Br
—H
—CF3


B197 (a and b)
S
—Br
—H
—OCH3


B198 (a and b)
S
—Br
—H
—OCH2CH3


B199 (a and b)
S
—Br
—H
—OCF3


B200 (a and b)
S
—Br
—H
-tert-butyl


B201 (a and b)
S
—Br
—H
-iso-propyl


B202 (a and b)
S
—I
—Cl
—H


B203 (a and b)
S
—I
—Br
—H


B204 (a and b)
S
—I
—F
—H


B205 (a and b)
S
—I
—CH3
—H


B206 (a and b)
S
—I
—CF3
—H


B207 (a and b)
S
—I
—OCH3
—H


B208 (a and b)
S
—I
—OCH2CH3
—H


B209 (a and b)
S
—I
—OCF3
—H


B210 (a and b)
S
—I
-tert-butyl
—H


B211 (a and b)
S
—I
-iso-propyl
—H


B212 (a and b)
S
—I
—CH3
—CH3


B213 (a and b)
S
—I
—H
—H


B214 (a and b)
S
—I
—H
—Cl


B215 (a and b)
S
—I
—H
—Br


B216 (a and b)
S
—I
—H
—F


B217 (a and b)
S
—I
—H
—CH3


B218 (a and b)
S
—I
—H
—CF3


B219 (a and b)
S
—I
—H
—OCH3


B220 (a and b)
S
—I
—H
—OCH2CH3


B221 (a and b)
S
—I
—H
—OCF3


B222 (a and b)
S
—I
—H
-tert-butyl


B223 (a and b)
S
—I
—H
-iso-propyl


B224 (a and b)
O
—H
—Cl
—H


B225 (a and b)
O
—H
—Br
—H


B226 (a and b)
O
—H
—F
—H


B227 (a and b)
O
—H
—CH3
—H


B228 (a and b)
O
—H
—CF3
—H


B229 (a and b)
O
—H
—OCH3
—H


B230 (a and b)
O
—H
—OCH2CH3
—H


B231 (a and b)
O
—H
—OCF3
—H


B232 (a and b)
O
—H
-tert-butyl
—H


B233 (a and b)
O
—H
-iso-propyl
—H


B234 (a and b)
O
—H
—CH3
—CH3


B235 (a and b)
O
—H
—H
—H


B236 (a and b)
O
—H
—H
—Cl


B237 (a and b)
O
—H
—H
—Br


B238 (a and b)
O
—H
—H
—F


B239 (a and b)
O
—H
—H
—CH3


B240 (a and b)
O
—H
—H
—CF3


B241 (a and b)
O
—H
—H
—OCH3


B242 (a and b)
O
—H
—H
—OCH2CH3


B243 (a and b)
O
—H
—H
—OCF3


B244 (a and b)
O
—H
—H
-tert-butyl


B245 (a and b)
O
—H
—H
-iso-propyl


B246 (a and b)
O
—Cl
—Cl
—H


B247 (a and b)
O
—Cl
—Br
—H


B248 (a and b)
O
—Cl
—F
—H


B249 (a and b)
O
—Cl
—CH3
—H


B250 (a and b)
O
—Cl
—CF3
—H


B251 (a and b)
O
—Cl
—OCH3
—H


B252 (a and b)
O
—Cl
—OCH2CH3
—H


B253 (a and b)
O
—Cl
—OCF3
—H


B254 (a and b)
O
—Cl
-tert-butyl
—H


B255 (a and b)
O
—Cl
-iso-propyl
—H


B256 (a and b)
O
—Cl
—CH3
—CH3


B257 (a and b)
O
—Cl
—H
—H


B258 (a and b)
O
—Cl
—H
—CH3


B259 (a and b)
O
—Cl
—H
—Cl


B260 (a and b)
O
—Cl
—H
—Br


B261 (a and b)
O
—Cl
—H
—F


B262 (a and b)
O
—Cl
—H
—CF3


B263 (a and b)
O
—Cl
—H
—OCH3


B264 (a and b)
O
—Cl
—H
—OCH2CH3


B265 (a and b)
O
—Cl
—H
—OCF3


B266 (a and b)
O
—Cl
—H
-tert-butyl


B267 (a and b)
O
—Cl
—H
-iso-propyl


B268 (a and b)
O
—Cl
—H
—OCF3


B269 (a and b)
O
—Cl
—H
-tert-butyl


B270 (a and b)
O
—Cl
—H
-iso-propyl


B271 (a and b)
O
—CH3
—Cl
—H


B272 (a and b)
O
—CH3
—Br
—H


B273 (a and b)
O
—CH3
—F
—H


B274 (a and b)
O
—CH3
—CH3
—H


B275 (a and b)
O
—CH3
—CF3
—H


B276 (a and b)
O
—CH3
—OCH3
—H


B277 (a and b)
O
—CH3
—OCH2CH3
—H


B278 (a and b)
O
—CH3
—OCF3
—H


B279 (a and b)
O
—CH3
-tert-butyl
—H


B280 (a and b)
O
—CH3
-iso-propyl
—H


B281 (a and b)
O
—CH3
—CH3
—CH3


B282 (a and b)
O
—CH3
—H
—H


B283 (a and b)
O
—CH3
—H
—Cl


B284 (a and b)
O
—CH3
—H
—Br


B285 (a and b)
O
—CH3
—H
—F


B286 (a and b)
O
—CH3
—H
—CH3


B287 (a and b)
O
—CH3
—H
—CF3


B288 (a and b)
O
—CH3
—H
—OCH3


B289 (a and b)
O
—CH3
—H
—OCH2CH3


B290 (a and b)
O
—CH3
—H
—OCF3


B291 (a and b)
O
—CH3
—H
-tert-butyl


B292 (a and b)
O
—CH3
—H
-iso-propyl


B293 (a and b)
O
—CF3
—Cl
—H


B294 (a and b)
O
—CF3
—Br
—H


B295 (a and b)
O
—CF3
—F
—H


B296 (a and b)
O
—CF3
—CH3
—H


B297 (a and b)
O
—CF3
—CF3
—H


B298 (a and b)
O
—CF3
—OCH3
—H


B299 (a and b)
O
—CF3
—OCH2CH3
—H


B300 (a and b)
O
—CF3
—OCF3
—H


B301 (a and b)
O
—CF3
-tert-butyl
—H


B302 (a and b)
O
—CF3
-iso-propyl
—H


B303 (a and b)
O
—CF3
—CH3
—CH3


B304 (a and b)
O
—CF3
—H
—H


B305 (a and b)
O
—CF3
—H
—Cl


B306 (a and b)
O
—CF3
—H
—Br


B307 (a and b)
O
—CF3
—H
—F


B308 (a and b)
O
—CF3
—H
—CH3


B309 (a and b)
O
—CF3
—H
—CF3


B310 (a and b)
O
—CF3
—H
—OCH3


B311 (a and b)
O
—CF3
—H
—OCH2CH3


B312 (a and b)
O
—CF3
—H
—OCF3


B313 (a and b)
O
—CF3
—H
-tert-butyl


B314 (a and b)
O
—CF3
—H
-iso-propyl


B315 (a and b)
O
—CHF2
—Cl
—H


B316 (a and b)
O
—CHF2
—Br
—H


B317 (a and b)
O
—CHF2
—F
—H


B318 (a and b)
O
—CHF2
—CH3
—H


B319 (a and b)
O
—CHF2
—CF3
—H


B320 (a and b)
O
—CHF2
—OCH3
—H


B321 (a and b)
O
—CHF2
—OCH2CH3
—H


B322 (a and b)
O
—CHF2
—OCF3
—H


B323 (a and b)
O
—CHF2
-tert-butyl
—H


B324 (a and b)
O
—CHF2
-iso-propyl
—H


B325 (a and b)
O
—CHF2
—CH3
—CH3


B326 (a and b)
O
—CHF2
—H
—H


B327 (a and b)
O
—CHF2
—H
—Cl


B328 (a and b)
O
—CHF2
—H
—Br


B329 (a and b)
O
—CHF2
—H
—F


B330 (a and b)
O
—CHF2
—H
—CH3


B331 (a and b)
O
—CHF2
—H
—CF3


B332 (a and b)
O
—CHF2
—H
—OCH3


B333 (a and b)
O
—CHF2
—H
—OCH2CH3


B334 (a and b)
O
—CHF2
—H
—OCF3


B335 (a and b)
O
—CHF2
—H
-tert-butyl


B336 (a and b)
O
—CHF2
—H
-iso-propyl


B337 (a and b)
O
—OH
—Cl
—H


B338 (a and b)
O
—OH
—Br
—H


B339 (a and b)
O
—OH
—F
—H


B340 (a and b)
O
—OH
—CH3
—H


B341 (a and b)
O
—OH
—CF3
—H


B342 (a and b)
O
—OH
—OCH3
—H


B343 (a and b)
O
—OH
—OCH2CH3
—H


B344 (a and b)
O
—OH
—OCF3
—H


B345 (a and b)
O
—OH
-tert-butyl
—H


B346 (a and b)
O
—OH
-iso-propyl
—H


B347 (a and b)
O
—OH
—CH3
—CH3


B348 (a and b)
O
—OH
—H
—H


B349 (a and b)
O
—OH
—H
—Cl


B350 (a and b)
O
—OH
—H
—Br


B351 (a and b)
O
—OH
—H
—F


B352 (a and b)
O
—OH
—H
—CH3


B353 (a and b)
O
—OH
—H
—CF3


B354 (a and b)
O
—OH
—H
—OCH3


B355 (a and b)
O
—OH
—H
—OCH2CH3


B356 (a and b)
O
—OH
—H
—OCF3


B357 (a and b)
O
—OH
—H
-tert-butyl


B358 (a and b)
O
—OH
—H
-iso-propyl


B359 (a and b)
O
—NO2
—Cl
—H


B360 (a and b)
O
—NO2
—Br
—H


B361 (a and b)
O
—NO2
—F
—H


B362 (a and b)
O
—NO2
—CH3
—H


B363 (a and b)
O
—NO2
—CF3
—H


B364 (a and b)
O
—NO2
—OCH3
—H


B365 (a and b)
O
—NO2
—OCH2CH3
—H


B366 (a and b)
O
—NO2
—OCF3
—H


B367 (a and b)
O
—NO2
-tert-butyl
—H


B368 (a and b)
O
—NO2
-iso-propyl
—H


B369 (a and b)
O
—NO2
—CH3
—CH3


B370 (a and b)
O
—NO2
—H
—H


B371 (a and b)
O
—NO2
—H
—Cl


B372 (a and b)
O
—NO2
—H
—Br


B373 (a and b)
O
—NO2
—H
—F


B374 (a and b)
O
—NO2
—H
—CH3


B375 (a and b)
O
—NO2
—H
—CF3


B376 (a and b)
O
—NO2
—H
—OCH3


B377 (a and b)
O
—NO2
—H
—OCH2CH3


B378 (a and b)
O
—NO2
—H
—OCF3


B379 (a and b)
O
—NO2
—H
-tert-butyl


B380 (a and b)
O
—NO2
—H
-iso-propyl


B381 (a and b)
O
—CN
—Br
—H


B382 (a and b)
O
—CN
—Cl
—H


B383 (a and b)
O
—CN
—F
—H


B384 (a and b)
O
—CN
—CH3
—H


B385 (a and b)
O
—CN
—CF3
—H


B386 (a and b)
O
—CN
—OCH3
—H


B387 (a and b)
O
—CN
—OCH2CH3
—H


B388 (a and b)
O
—CN
—OCF3
—H


B389 (a and b)
O
—CN
-tert-butyl
—H


B390 (a and b)
O
—CN
-iso-propyl
—H


B391 (a and b)
O
—CN
—CH3
—CH3


B392 (a and b)
O
—CN
—H
—H


B393 (a and b)
O
—CN
—H
—Cl


B394 (a and b)
O
—CN
—H
—Br


B395 (a and b)
O
—CN
—H
—F


B396 (a and b)
O
—CN
—H
—CH3


B397 (a and b)
O
—CN
—H
—CF3


B398 (a and b)
O
—CN
—H
—OCH3


B399 (a and b)
O
—CN
—H
—OCH2CH3


B400 (a and b)
O
—CN
—H
—OCF3


B401 (a and b)
O
—CN
—H
-tert-butyl


B402 (a and b)
O
—CN
—H
-iso-propyl


B403 (a and b)
O
—Br
—Br
—H


B404 (a and b)
O
—Br
—Cl
—H


B405 (a and b)
O
—Br
—F
—H


B406 (a and b)
O
—Br
—CH3
—H


B407 (a and b)
O
—Br
—CF3
—H


B408 (a and b)
O
—Br
—OCH3
—H


B409 (a and b)
O
—Br
—OCH2CH3
—H


B410 (a and b)
O
—Br
—OCF3
—H


B411 (a and b)
O
—Br
-tert-butyl
—H


B412 (a and b)
O
—Br
-iso-propyl
—H


B413 (a and b)
O
—Br
—CH3
—CH3


B414 (a and b)
O
—Br
—H
—H


B415 (a and b)
O
—Br
—H
—Cl


B416 (a and b)
O
—Br
—H
—Br


B417 (a and b)
O
—Br
—H
—F


B418 (a and b)
O
—Br
—H
—CH3


B419 (a and b)
O
—Br
—H
—CF3


B420 (a and b)
O
—Br
—H
—OCH3


B421 (a and b)
O
—Br
—H
—OCH2CH3


B422 (a and b)
O
—Br
—H
—OCF3


B423 (a and b)
O
—Br
—H
-tert-butyl


B424 (a and b)
O
—Br
—H
-iso-propyl


B425 (a and b)
O
—I
—Cl
—H


B426 (a and b)
O
—I
—Br
—H


B427 (a and b)
O
—I
—F
—H


B428 (a and b)
O
—I
—CH3
—H


B429 (a and b)
O
—I
—CF3
—H


B430 (a and b)
O
—I
—OCH3
—H


B431 (a and b)
O
—I
—OCH2CH3
—H


B432 (a and b)
O
—I
—OCF3
—H


B433 (a and b)
O
—I
-tert-butyl
—H


B434 (a and b)
O
—I
-iso-propyl
—H


B435 (a and b)
O
—I
—CH3
—CH3


B436 (a and b)
O
—I
—H
—H


B437 (a and b)
O
—I
—H
—Cl


B438 (a and b)
O
—I
—H
—Br


B439 (a and b)
O
—I
—H
—F


B440 (a and b)
O
—I
—H
—CH3


B441 (a and b)
O
—I
—H
—CF3


B442 (a and b)
O
—I
—H
—OCH3


B443 (a and b)
O
—I
—H
—OCH2CH3


B444 (a and b)
O
—I
—H
—OCF3


B445 (a and b)
O
—I
—H
-tert-butyl


B446 (a and b)
O
—I
—H
-iso-propyl


B447 (a and b)
NH
—H
—Cl
—H


B448 (a and b)
NH
—H
—Br
—H


B449 (a and b)
NH
—H
—F
—H


B450 (a and b)
NH
—H
—CH3
—H


B451 (a and b)
NH
—H
—CF3
—H


B452 (a and b)
NH
—H
—OCH3
—H


B453 (a and b)
NH
—H
—OCH2CH3
—H


B454 (a and b)
NH
—H
—OCF3
—H


B455 (a and b)
NH
—H
-tert-butyl
—H


B456 (a and b)
NH
—H
-iso-propyl
—H


B457 (a and b)
NH
—H
—CH3
—CH3


B458 (a and b)
NH
—H
—H
—H


B459 (a and b)
NH
—H
—H
—Cl


B460 (a and b)
NH
—H
—H
—Br


B461 (a and b)
NH
—H
—H
—F


B462 (a and b)
NH
—H
—H
—CH3


B463 (a and b)
NH
—H
—H
—CF3


B464 (a and b)
NH
—H
—H
—OCH3


B465 (a and b)
NH
—H
—H
—OCH2CH3


B466 (a and b)
NH
—H
—H
—OCF3


B467 (a and b)
NH
—H
—H
-tert-butyl


B468 (a and b)
NH
—H
—H
-iso-propyl


B469 (a and b)
NH
—Cl
—Cl
—H


B470 (a and b)
NH
—Cl
—Br
—H


B471 (a and b)
NH
—Cl
—F
—H


B472 (a and b)
NH
—Cl
—CH3
—H


B473 (a and b)
NH
—Cl
—CF3
—H


B474 (a and b)
NH
—Cl
—OCH3
—H


B475 (a and b)
NH
—Cl
—OCH2CH3
—H


B476 (a and b)
NH
—Cl
—OCF3
—H


B477 (a and b)
NH
—Cl
-tert-butyl
—H


B478 (a and b)
NH
—Cl
-iso-propyl
—H


B479 (a and b)
NH
—Cl
—CH3
—CH3


B480 (a and b)
NH
—Cl
—H
—H


B481 (a and b)
NH
—Cl
—H
—CH3


B482 (a and b)
NH
—Cl
—H
—Cl


B483 (a and b)
NH
—Cl
—H
—Br


B484 (a and b)
NH
—Cl
—H
—F


B485 (a and b)
NH
—Cl
—H
—CF3


B486 (a and b)
NH
—Cl
—H
—OCH3


B487 (a and b)
NH
—Cl
—H
—OCH2CH3


B488 (a and b)
NH
—Cl
—H
—OCF3


B489 (a and b)
NH
—Cl
—H
-tert-butyl


B490 (a and b)
NH
—Cl
—H
-iso-propyl


B491 (a and b)
NH
—Cl
—H
—OCF3


B492 (a and b)
NH
—Cl
—H
-tert-butyl


B493 (a and b)
NH
—Cl
—H
-iso-propyl


B494 (a and b)
NH
—CH3
—Cl
—H


B495 (a and b)
NH
—CH3
—Br
—H


B496 (a and b)
NH
—CH3
—F
—H


B497 (a and b)
NH
—CH3
—CH3
—H


B498 (a and b)
NH
—CH3
—CF3
—H


B499 (a and b)
NH
—CH3
—OCH3
—H


B500 (a and b)
NH
—CH3
—OCH2CH3
—H


B501 (a and b)
NH
—CH3
—OCF3
—H


B502 (a and b)
NH
—CH3
-tert-butyl
—H


B503 (a and b)
NH
—CH3
-iso-propyl
—H


B504 (a and b)
NH
—CH3
—CH3
—CH3


B505 (a and b)
NH
—CH3
—H
—H


B506 (a and b)
NH
—CH3
—H
—Cl


B507 (a and b)
NH
—CH3
—H
—Br


B508 (a and b)
NH
—CH3
—H
—F


B509 (a and b)
NH
—CH3
—H
—CH3


B510 (a and b)
NH
—CH3
—H
—CF3


B511 (a and b)
NH
—CH3
—H
—OCH3


B512 (a and b)
NH
—CH3
—H
—OCH2CH3


B513 (a and b)
NH
—CH3
—H
—OCF3


B514 (a and b)
NH
—CH3
—H
-tert-butyl


B515 (a and b)
NH
—CH3
—H
-iso-propyl


B516 (a and b)
NH
—CF3
—Cl
—H


B517 (a and b)
NH
—CF3
—Br
—H


B518 (a and b)
NH
—CF3
—F
—H


B519 (a and b)
NH
—CF3
—CH3
—H


B520 (a and b)
NH
—CF3
—CF3
—H


B521 (a and b)
NH
—CF3
—OCH3
—H


B522 (a and b)
NH
—CF3
—OCH2CH3
—H


B523 (a and b)
NH
—CF3
—OCF3
—H


B524 (a and b)
NH
—CF3
-tert-butyl
—H


B525 (a and b)
NH
—CF3
-iso-propyl
—H


B526 (a and b)
NH
—CF3
—CH3
—CH3


B527 (a and b)
NH
—CF3
—H
—H


B528 (a and b)
NH
—CF3
—H
—Cl


B529 (a and b)
NH
—CF3
—H
—Br


B530 (a and b)
NH
—CF3
—H
—F


B531 (a and b)
NH
—CF3
—H
—CH3


B532 (a and b)
NH
—CF3
—H
—CF3


B533 (a and b)
NH
—CF3
—H
—OCH3


B534 (a and b)
NH
—CF3
—H
—OCH2CH3


B535 (a and b)
NH
—CF3
—H
—OCF3


B536 (a and b)
NH
—CF3
—H
-tert-butyl


B537 (a and b)
NH
—CF3
—H
-iso-propyl


B538 (a and b)
NH
—CHF2
—Cl
—H


B539 (a and b)
NH
—CHF2
—Br
—H


B540 (a and b)
NH
—CHF2
—F
—H


B541 (a and b)
NH
—CHF2
—CH3
—H


B542 (a and b)
NH
—CHF2
—CF3
—H


B543 (a and b)
NH
—CHF2
—OCH3
—H


B544 (a and b)
NH
—CHF2
—OCH2CH3
—H


B545 (a and b)
NH
—CHF2
—OCF3
—H


B546 (a and b)
NH
—CHF2
-tert-butyl
—H


B547 (a and b)
NH
—CHF2
-iso-propyl
—H


B548 (a and b)
NH
—CHF2
—CH3
—CH3


B549 (a and b)
NH
—CHF2
—H
—H


B550 (a and b)
NH
—CHF2
—H
—Cl


B551 (a and b)
NH
—CHF2
—H
—Br


B552 (a and b)
NH
—CHF2
—H
—F


B553 (a and b)
NH
—CHF2
—H
—CH3


B554 (a and b)
NH
—CHF2
—H
—CF3


B555 (a and b)
NH
—CHF2
—H
—OCH3


B556 (a and b)
NH
—CHF2
—H
—OCH2CH3


B557 (a and b)
NH
—CHF2
—H
—OCF3


B558 (a and b)
NH
—CHF2
—H
-tert-butyl


B559 (a and b)
NH
—CHF2
—H
-iso-propyl


B560 (a and b)
NH
—OH
—Cl
—H


B561 (a and b)
NH
—OH
—Br
—H


B562 (a and b)
NH
—OH
—F
—H


B563 (a and b)
NH
—OH
—CH3
—H


B564 (a and b)
NH
—OH
—CF3
—H


B565 (a and b)
NH
—OH
—OCH3
—H


B566 (a and b)
NH
—OH
—OCH2CH3
—H


B567 (a and b)
NH
—OH
—OCF3
—H


B568 (a and b)
NH
—OH
-tert-butyl
—H


B569 (a and b)
NH
—OH
-iso-propyl
—H


B570 (a and b)
NH
—OH
—CH3
—CH3


B571 (a and b)
NH
—OH
—H
—H


B572 (a and b)
NH
—OH
—H
—Cl


B573 (a and b)
NH
—OH
—H
—Br


B574 (a and b)
NH
—OH
—H
—F


B575 (a and b)
NH
—OH
—H
—CH3


B576 (a and b)
NH
—OH
—H
—CF3


B577 (a and b)
NH
—OH
—H
—OCH3


B578 (a and b)
NH
—OH
—H
—OCH2CH3


B579 (a and b)
NH
—OH
—H
—OCF3


B580 (a and b)
NH
—OH
—H
-tert-butyl


B581 (a and b)
NH
—OH
—H
-iso-propyl


B582 (a and b)
NH
—NO2
—Cl
—H


B583 (a and b)
NH
—NO2
—Br
—H


B584 (a and b)
NH
—NO2
—F
—H


B585 (a and b)
NH
—NO2
—CH3
—H


B586 (a and b)
NH
—NO2
—CF3
—H


B587 (a and b)
NH
—NO2
—OCH3
—H


B588 (a and b)
NH
—NO2
—OCH2CH3
—H


B589 (a and b)
NH
—NO2
—OCF3
—H


B590 (a and b)
NH
—NO2
-tert-butyl
—H


B591 (a and b)
NH
—NO2
-iso-propyl
—H


B592 (a and b)
NH
—NO2
—CH3
—CH3


B593 (a and b)
NH
—NO2
—H
—H


B594 (a and b)
NH
—NO2
—H
—Cl


B595 (a and b)
NH
—NO2
—H
—Br


B596 (a and b)
NH
—NO2
—H
—F


B597 (a and b)
NH
—NO2
—H
—CH3


B598 (a and b)
NH
—NO2
—H
—CF3


B599 (a and b)
NH
—NO2
—H
—OCH3


B600 (a and b)
NH
—NO2
—H
—OCH2CH3


B601 (a and b)
NH
—NO2
—H
—OCF3


B602 (a and b)
NH
—NO2
—H
-tert-butyl


B603 (a and b)
NH
—NO2
—H
-iso-propyl


B604 (a and b)
NH
—CN
—Br
—H


B605 (a and b)
NH
—CN
—Cl
—H


B606 (a and b)
NH
—CN
—F
—H


B607 (a and b)
NH
—CN
—CH3
—H


B608 (a and b)
NH
—CN
—CF3
—H


B609 (a and b)
NH
—CN
—OCH3
—H


B610 (a and b)
NH
—CN
—OCH2CH3
—H


B611 (a and b)
NH
—CN
—OCF3
—H


B612 (a and b)
NH
—CN
-tert-butyl
—H


B613 (a and b)
NH
—CN
-iso-propyl
—H


B614 (a and b)
NH
—CN
—CH3
—CH3


B615 (a and b)
NH
—CN
—H
—H


B616 (a and b)
NH
—CN
—H
—Cl


B617 (a and b)
NH
—CN
—H
—Br


B618 (a and b)
NH
—CN
—H
—F


B619 (a and b)
NH
—CN
—H
—CH3


B620 (a and b)
NH
—CN
—H
—CF3


B621 (a and b)
NH
—CN
—H
—OCH3


B622 (a and b)
NH
—CN
—H
—OCH2CH3


B623 (a and b)
NH
—CN
—H
—OCF3


B624 (a and b)
NH
—CN
—H
-tert-butyl


B625 (a and b)
NH
—CN
—H
-iso-propyl


B626 (a and b)
NH
—Br
—Br
—H


B627 (a and b)
NH
—Br
—Cl
—H


B628 (a and b)
NH
—Br
—F
—H


B629 (a and b)
NH
—Br
—CH3
—H


B630 (a and b)
NH
—Br
—CF3
—H


B631 (a and b)
NH
—Br
—OCH3
—H


B632 (a and b)
NH
—Br
—OCH2CH3
—H


B633 (a and b)
NH
—Br
—OCF3
—H


B634 (a and b)
NH
—Br
-tert-butyl
—H


B635 (a and b)
NH
—Br
-iso-propyl
—H


B636 (a and b)
NH
—Br
—CH3
—CH3


B637 (a and b)
NH
—Br
—H
—H


B638 (a and b)
NH
—Br
—H
—Cl


B639 (a and b)
NH
—Br
—H
—Br


B640 (a and b)
NH
—Br
—H
—F


B641 (a and b)
NH
—Br
—H
—CH3


B642 (a and b)
NH
—Br
—H
—CF3


B643 (a and b)
NH
—Br
—H
—OCH3


B644 (a and b)
NH
—Br
—H
—OCH2CH3


B645 (a and b)
NH
—Br
—H
—OCF3


B646 (a and b)
NH
—Br
—H
-tert-butyl


B647 (a and b)
NH
—Br
—H
-iso-propyl


B648 (a and b)
NH
—I
—Cl
—H


B649 (a and b)
NH
—I
—Br
—H


B650 (a and b)
NH
—I
—F
—H


B651 (a and b)
NH
—I
—CH3
—H


B652 (a and b)
NH
—I
—CF3
—H


B653 (a and b)
NH
—I
—OCH3
—H


B654 (a and b)
NH
—I
—OCH2CH3
—H


B655 (a and b)
NH
—I
—OCF3
—H


B656 (a and b)
NH
—I
-tert-butyl
—H


B657 (a and b)
NH
—I
-iso-propyl
—H


B658 (a and b)
NH
—I
—CH3
—CH3


B659 (a and b)
NH
—I
—H
—H


B660 (a and b)
NH
—I
—H
—Cl


B661 (a and b)
NH
—I
—H
—Br


B662 (a and b)
NH
—I
—H
—F


B663 (a and b)
NH
—I
—H
—CH3


B664 (a and b)
NH
—I
—H
—CF3


B665 (a and b)
NH
—I
—H
—OCH3


B666 (a and b)
NH
—I
—H
—OCH2CH3


B667 (a and b)
NH
—I
—H
—OCF3


B668 (a and b)
NH
—I
—H
-tert-butyl


B669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 3








(Ic)




embedded image













and pharmaceutically acceptable salts thereof, wherein:









Compound
R1
R8a





C01 (a and b)
—H
—H


C02 (a and b)
—H
-tert-butyl


C03 (a and b)
—H
-iso-butyl


C04 (a and b)
—H
-sec-butyl


C05 (a and b)
—H
-iso-propyl


C06 (a and b)
—H
-n-propyl


C07 (a and b)
—H
-cyclohexyl


C08 (a and b)
—H
-tert-butoxy


C09 (a and b)
—H
-isopropoxy


C10 (a and b)
—H
—CF3


C11 (a and b)
—H
—CH2CF3


C12 (a and b)
—H
—OCF3


C13 (a and b)
—H
—Cl


C14 (a and b)
—H
—Br


C15 (a and b)
—H
—I


C16 (a and b)
—H
-n-butyl


C17 (a and b)
—H
—CH3


C18 (a and b)
—H
—SCF3


C19 (a and b)
—H
—N(CH2CH3)2


C20 (a and b)
—H
—OCF2CHF2


C21 (a and b)
—H
—C(OH)(CF3)2


C22 (a and b)
—H
-(1,1-dimethyl-pentyl)


C23 (a and b)
—H
-(1,1-dimethyl-acetic acid) ethyl ester


C24 (a and b)
—H
—N-piperidinyl


C25 (a and b)
—Cl
—H


C26 (a and b)
—Cl
-tert-butyl


C27 (a and b)
—Cl
-iso-butyl


C28 (a and b)
—Cl
-sec-butyl


C29 (a and b)
—Cl
-iso-propyl


C30 (a and b)
—Cl
-n-propyl


C31 (a and b)
—Cl
-cyclohexyl


C32 (a and b)
—Cl
-tert-butoxy


C33 (a and b)
—Cl
-isopropoxy


C34 (a and b)
—Cl
—CF3


C35 (a and b)
—Cl
—CH2CF3


C36 (a and b)
—Cl
—OCF3


C37 (a and b)
—Cl
—Cl


C38 (a and b)
—Cl
—Br


C39 (a and b)
—Cl
—I


C40 (a and b)
—Cl
-n-butyl


C41 (a and b)
—Cl
—CH3


C42 (a and b)
—Cl
—SCF3


C43 (a and b)
—Cl
—N(CH2CH3)2


C44 (a and b)
—Cl
—OCF2CHF2


C45 (a and b)
—Cl
—C(OH)(CF3)2


C46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)


C47 (a and b)
—Cl
-(1,1-dimethyl-acetic acid) ethyl ester


C48 (a and b)
—Cl
—N-piperidinyl


C49 (a and b)
—F
—H


C50 (a and b)
—F
-tert-butyl


C51 (a and b)
—F
-iso-butyl


C52 (a and b)
—F
-sec-butyl


C53 (a and b)
—F
-iso-propyl


C54 (a and b)
—F
-n-propyl


C55 (a and b)
—F
-cyclohexyl


C56 (a and b)
—F
-tert-butoxy


C57 (a and b)
—F
-isopropoxy


C58 (a and b)
—F
—CF3


C59 (a and b)
—F
—CH2CF3


C60 (a and b)
—F
—OCF3


C61 (a and b)
—F
—Cl


C62 (a and b)
—F
—Br


C63 (a and b)
—F
—I


C64 (a and b)
—F
-n-butyl


C65 (a and b)
—F
—CH3


C66 (a and b)
—F
—SCF3


C67 (a and b)
—F
—N(CH2CH3)2


C68 (a and b)
—F
—OCF2CHF2


C69 (a and b)
—F
—C(OH)(CF3)2


C70 (a and b)
—F
-(1,1-dimethyl-pentyl)


C71 (a and b)
—F
-(1,1-dimethyl-acetic acid) ethyl ester


C72 (a and b)
—F
—N-piperidinyl


C73 (a and b)
—CH3
—H


C74 (a and b)
—CH3
-iso-butyl


C75 (a and b)
—CH3
-tert-butyl


C76 (a and b)
—CH3
-sec-butyl


C77 (a and b)
—CH3
-iso-propyl


C78 (a and b)
—CH3
-n-propyl


C79 (a and b)
—CH3
-cyclohexyl


C80 (a and b)
—CH3
-tert-butoxy


C81 (a and b)
—CH3
-isopropoxy


C82 (a and b)
—CH3
—CF3


C83 (a and b)
—CH3
—CH2CF3


C84 (a and b)
—CH3
—OCF3


C85 (a and b)
—CH3
—Cl


C86 (a and b)
—CH3
—Br


C87 (a and b)
—CH3
—I


C88 (a and b)
—CH3
-n-butyl


C89 (a and b)
—CH3
—CH3


C90 (a and b)
—CH3
—SCF3


C91 (a and b)
—CH3
—N(CH2CH3)2


C92 (a and b)
—CH3
—OCF2CHF2


C93 (a and b)
—CH3
—C(OH)(CF3)2


C94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)


C95 (a and b)
—CH3
-(1,1-dimethyl-acetic acid) ethyl ester


C96 (a and b)
—CH3
—N-piperidinyl


C97 (a and b)
—CF3
—H


C98 (a and b)
—CF3
-tert-butyl


C99 (a and b)
—CF3
-iso-butyl


C100 (a and b)
—CF3
-sec-butyl


C101 (a and b)
—CF3
-iso-propyl


C102 (a and b)
—CF3
-n-propyl


C103 (a and b)
—CF3
-cyclohexyl


C104 (a and b)
—CF3
-tert-butoxy


C105 (a and b)
—CF3
-isopropoxy


C106 (a and b)
—CF3
—CF3


C107 (a and b)
—CF3
—CH2CF3


C108 (a and b)
—CF3
—OCF3


C109 (a and b)
—CF3
—Cl


C110 (a and b)
—CF3
—Br


C111 (a and b)
—CF3
—I


C112 (a and b)
—CF3
-n-butyl


C113 (a and b)
—CF3
—CH3


C114 (a and b)
—CF3
—SCF3


C115 (a and b)
—CF3
—N(CH2CH3)2


C116 (a and b)
—CF3
—OCF2CHF2


C117 (a and b)
—CF3
—C(OH)(CF3)2


C118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)


C119 (a and b)
—CF3
-(1,1-dimethyl-acetic acid) ethyl ester


C120 (a and b)
—CF3
—N-piperidinyl


C121 (a and b)
—CHF2
-tert-butyl


C122 (a and b)
—CHF2
—H


C123 (a and b)
—CHF2
-iso-butyl


C124 (a and b)
—CHF2
-sec-butyl


C125 (a and b)
—CHF2
-iso-propyl


C126 (a and b)
—CHF2
-n-propyl


C127 (a and b)
—CHF2
-cyclohexyl


C128 (a and b)
—CHF2
-tert-butoxy


C129 (a and b)
—CHF2
-isopropoxy


C130 (a and b)
—CHF2
—CF3


C131 (a and b)
—CHF2
—CH2CF3


C132 (a and b)
—CHF2
—OCF3


C133 (a and b)
—CHF2
—Cl


C134 (a and b)
—CHF2
—Br


C135 (a and b)
—CHF2
—I


C136 (a and b)
—CHF2
-n-butyl


C137 (a and b)
—CHF2
—CH3


C138 (a and b)
—CHF2
—SCF3


C139 (a and b)
—CHF2
—N(CH2CH3)2


C140 (a and b)
—CHF2
—OCF2CHF2


C141 (a and b)
—CHF2
—C(OH)(CF3)2


C142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)


C143 (a and b)
—CHF2
-(1,1-dimethyl-acetic acid) ethyl ester


C144 (a and b)
—CHF2
—N-piperidinyl


C145 (a and b)
—OH
—H


C146 (a and b)
—OH
-tert-butyl


C147 (a and b)
—OH
-iso-butyl


C148 (a and b)
—OH
-sec-butyl


C149 (a and b)
—OH
-iso-propyl


C150 (a and b)
—OH
-n-propyl


C151 (a and b)
—OH
-cyclohexyl


C152 (a and b)
—OH
-tert-butoxy


C153 (a and b)
—OH
-isopropoxy


C154 (a and b)
—OH
—CF3


C155 (a and b)
—OH
—CH2CF3


C156 (a and b)
—OH
—OCF3


C157 (a and b)
—OH
—Cl


C158 (a and b)
—OH
—Br


C159 (a and b)
—OH
—I


C160 (a and b)
—OH
-n-butyl


C161 (a and b)
—OH
—CH3


C162 (a and b)
—OH
—SCF3


C163 (a and b)
—OH
—N(CH2CH3)2


C164 (a and b)
—OH
—OCF2CHF2


C165 (a and b)
—OH
—C(OH)(CF3)2


C166 (a and b)
—OH
-(1,1-dimethyl-pentyl)


C167 (a and b)
—OH
-(1,1-dimethyl-acetic acid) ethyl ester


C168 (a and b)
—OH
—N-piperidinyl


C169 (a and b)
—NO2
—H


C170 (a and b)
—NO2
-tert-butyl


C171 (a and b)
—NO2
-iso-butyl


C172 (a and b)
—NO2
-sec-butyl


C173 (a and b)
—NO2
-iso-propyl


C174 (a and b)
—NO2
-n-propyl


C175 (a and b)
—NO2
-cyclohexyl


C176 (a and b)
—NO2
-tert-butoxy


C177 (a and b)
—NO2
-isopropoxy


C178 (a and b)
—NO2
—CF3


C179 (a and b)
—NO2
—CH2CF3


C180 (a and b)
—NO2
—OCF3


C181 (a and b)
—NO2
—Cl


C182 (a and b)
—NO2
—Br


C183 (a and b)
—NO2
—I


C184 (a and b)
—NO2
-n-butyl


C185 (a and b)
—NO2
—CH3


C186 (a and b)
—NO2
—SCF3


C187 (a and b)
—NO2
—N(CH2CH3)2


C188 (a and b)
—NO2
—OCF2CHF2


C189 (a and b)
—NO2
—C(OH)(CF3)2


C190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)


C191 (a and b)
—NO2
-(1,1-dimethyl-acetic acid) ethyl ester


C192 (a and b)
—NO2
—N-piperidinyl


C193 (a and b)
—CN
—H


C194 (a and b)
—CN
-tert-butyl


C195 (a and b)
—CN
-iso-butyl


C196 (a and b)
—CN
-sec-butyl


C197 (a and b)
—CN
-iso-propyl


C198 (a and b)
—CN
-n-propyl


C199 (a and b)
—CN
-cyclohexyl


C200 (a and b)
—CN
-tert-butoxy


C201 (a and b)
—CN
-isopropoxy


C202 (a and b)
—CN
—CF3


C203 (a and b)
—CN
—CH2CF3


C204 (a and b)
—CN
—OCF3


C205 (a and b)
—CN
—Cl


C206 (a and b)
—CN
—Br


C207 (a and b)
—CN
—I


C208 (a and b)
—CN
-n-butyl


C209 (a and b)
—CN
—CH3


C210 (a and b)
—CN
—SCF3


C211 (a and b)
—CN
—N(CH2CH3)2


C212 (a and b)
—CN
—OCF2CHF2


C213 (a and b)
—CN
—C(OH)(CF3)2


C214 (a and b)
—CN
-(1,1-dimethyl-pentyl)


C215 (a and b)
—CN
-(1,1-dimethyl-acetic acid) ethyl ester


C216 (a and b)
—CN
—N-piperidinyl


C217 (a and b)
—Br
—H


C218 (a and b)
—Br
-tert-butyl


C219 (a and b)
—Br
-iso-butyl


C220 (a and b)
—Br
-sec-butyl


C221 (a and b)
—Br
-iso-propyl


C222 (a and b)
—Br
-n-propyl


C223 (a and b)
—Br
-cyclohexyl


C224 (a and b)
—Br
-tert-butoxy


C225 (a and b)
—Br
-isopropoxy


C226 (a and b)
—Br
—CF3


C227 (a and b)
—Br
—CH2CF3


C228 (a and b)
—Br
—OCF3


C229 (a and b)
—Br
—Cl


C230 (a and b)
—Br
—Br


C231 (a and b)
—Br
—I


C232 (a and b)
—Br
-n-butyl


C233 (a and b)
—Br
—CH3


C234 (a and b)
—Br
—SCF3


C235 (a and b)
—Br
—N(CH2CH3)2


C236 (a and b)
—Br
—OCF2CHF2


C237 (a and b)
—Br
—C(OH)(CF3)2


C238 (a and b)
—Br
-(1,1-dimethyl-pentyl)


C239 (a and b)
—Br
-(1,1-dimethyl-acetic acid) ethyl ester


C240 (a and b)
—Br
—N-piperidinyl


C241 (a and b)
—I
-tert-butyl


C242 (a and b)
—I
—H


C243 (a and b)
—I
-iso-butyl


C244 (a and b)
—I
-sec-butyl


C245 (a and b)
—I
-iso-propyl


C246 (a and b)
—I
-n-propyl


C247 (a and b)
—I
-cyclohexyl


C248 (a and b)
—I
-tert-butoxy


C249 (a and b)
—I
-isopropoxy


C250 (a and b)
—I
—CF3


C251 (a and b)
—I
—CH2CF3


C252 (a and b)
—I
—OCF3


C253 (a and b)
—I
—Cl


C254 (a and b)
—I
—Br


C255 (a and b)
—I
—I


C256 (a and b)
—I
-n-butyl


C257 (a and b)
—I
—CH3


C258 (a and b)
—I
—SCF3


C259 (a and b)
—I
—N(CH2CH3)2


C260 (a and b)
—I
—OCF2CHF2


C261 (a and b)
—I
—C(OH)(CF3)2


C262 (a and b)
—I
-(1,1-dimethyl-pentyl)


C263 (a and b)
—I
-(1,1-dimethyl-acetic acid) ethyl ester


C264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 4








(Id)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
Y
R1
(R8)a
(R8)b





D01 (a and b)
S
—H
—Cl
—H


D02 (a and b)
S
—H
—Br
—H


D03 (a and b)
S
—H
—F
—H


D04 (a and b)
S
—H
—CH3
—H


D05 (a and b)
S
—H
—CF3
—H


D06 (a and b)
S
—H
—OCH3
—H


D07 (a and b)
S
—H
—OCH2CH3
—H


D08 (a and b)
S
—H
—OCF3
—H


D09 (a and b)
S
—H
-tert-butyl
—H


D10 (a and b)
S
—H
-iso-propyl
—H


D11 (a and b)
S
—H
—CH3
—CH3


D12 (a and b)
S
—H
—H
—H


D13 (a and b)
S
—H
—H
—Cl


D14 (a and b)
S
—H
—H
—Br


D15 (a and b)
S
—H
—H
—F


D16 (a and b)
S
—H
—H
—CH3


D17 (a and b)
S
—H
—H
—CF3


D18 (a and b)
S
—H
—H
—OCH3


D19 (a and b)
S
—H
—H
—OCH2CH3


D20 (a and b)
S
—H
—H
—OCF3


D21 (a and b)
S
—H
—H
-tert-butyl


D22 (a and b)
S
—H
—H
-iso-propyl


D23 (a and b)
S
—Cl
—Cl
—H


D24 (a and b)
S
—Cl
—Br
—H


D25 (a and b)
S
—Cl
—F
—H


D26 (a and b)
S
—Cl
—CH3
—H


D27 (a and b)
S
—Cl
—CF3
—H


D28 (a and b)
S
—Cl
—OCH3
—H


D29 (a and b)
S
—Cl
—OCH2CH3
—H


D30 (a and b)
S
—Cl
—OCF3
—H


D31 (a and b)
S
—Cl
-tert-butyl
—H


D32 (a and b)
S
—Cl
-iso-propyl
—H


D33 (a and b)
S
—Cl
—CH3
—CH3


D34 (a and b)
S
—Cl
—H
—H


D35 (a and b)
S
—Cl
—H
—CH3


D36 (a and b)
S
—Cl
—H
—Cl


D37 (a and b)
S
—Cl
—H
—Br


D38 (a and b)
S
—Cl
—H
—F


D39 (a and b)
S
—Cl
—H
—CF3


D40 (a and b)
S
—Cl
—H
—OCH3


D41 (a and b)
S
—Cl
—H
—OCH2CH3


D42 (a and b)
S
—Cl
—H
—OCF3


D43 (a and b)
S
—Cl
—H
-tert-butyl


D44 (a and b)
S
—Cl
—H
-iso-propyl


D45 (a and b)
S
—Cl
—H
—OCF3


D46 (a and b)
S
—Cl
—H
-tert-butyl


D47 (a and b)
S
—Cl
—H
-iso-propyl


D48 (a and b)
S
—CH3
—Cl
—H


D49 (a and b)
S
—CH3
—Br
—H


D50 (a and b)
S
—CH3
—F
—H


D51 (a and b)
S
—CH3
—CH3
—H


D52 (a and b)
S
—CH3
—CF3
—H


D53 (a and b)
S
—CH3
—OCH3
—H


D54 (a and b)
S
—CH3
—OCH2CH3
—H


D55 (a and b)
S
—CH3
—OCF3
—H


D56 (a and b)
S
—CH3
-tert-butyl
—H


D57 (a and b)
S
—CH3
-iso-propyl
—H


D58 (a and b)
S
—CH3
—CH3
—CH3


D59 (a and b)
S
—CH3
—H
—H


D60 (a and b)
S
—CH3
—H
—Cl


D61 (a and b)
S
—CH3
—H
—Br


D62 (a and b)
S
—CH3
—H
—F


D63 (a and b)
S
—CH3
—H
—CH3


D64 (a and b)
S
—CH3
—H
—CF3


D65 (a and b)
S
—CH3
—H
—OCH3


D66 (a and b)
S
—CH3
—H
—OCH2CH3


D67 (a and b)
S
—CH3
—H
—OCF3


D68 (a and b)
S
—CH3
—H
-tert-butyl


D69 (a and b)
S
—CH3
—H
-iso-propyl


D70 (a and b)
S
—CF3
—Cl
—H


D71 (a and b)
S
—CF3
—Br
—H


D72 (a and b)
S
—CF3
—F
—H


D73 (a and b)
S
—CF3
—CH3
—H


D74 (a and b)
S
—CF3
—CF3
—H


D75 (a and b)
S
—CF3
—OCH3
—H


D76 (a and b)
S
—CF3
—OCH2CH3
—H


D77 (a and b)
S
—CF3
—OCF3
—H


D78 (a and b)
S
—CF3
-tert-butyl
—H


D79 (a and b)
S
—CF3
-iso-propyl
—H


D80 (a and b)
S
—CF3
—CH3
—CH3


D81 (a and b)
S
—CF3
—H
—H


D82 (a and b)
S
—CF3
—H
—Cl


D83 (a and b)
S
—CF3
—H
—Br


D84 (a and b)
S
—CF3
—H
—F


D85 (a and b)
S
—CF3
—H
—CH3


D86 (a and b)
S
—CF3
—H
—CF3


D87 (a and b)
S
—CF3
—H
—OCH3


D88 (a and b)
S
—CF3
—H
—OCH2CH3


D89 (a and b)
S
—CF3
—H
—OCF3


D90 (a and b)
S
—CF3
—H
-tert-butyl


D91 (a and b)
S
—CF3
—H
-iso-propyl


D92 (a and b)
S
—CHF2
—Cl
—H


D93 (a and b)
S
—CHF2
—Br
—H


D94 (a and b)
S
—CHF2
—F
—H


D95 (a and b)
S
—CHF2
—CH3
—H


D96 (a and b)
S
—CHF2
—CF3
—H


D97 (a and b)
S
—CHF2
—OCH3
—H


D98 (a and b)
S
—CHF2
—OCH2CH3
—H


D99 (a and b)
S
—CHF2
—OCF3
—H


D100 (a and b)
S
—CHF2
-tert-butyl
—H


D101 (a and b)
S
—CHF2
-iso-propyl
—H


D102 (a and b)
S
—CHF2
—CH3
—CH3


D103 (a and b)
S
—CHF2
—H
—H


D104 (a and b)
S
—CHF2
—H
—Cl


D105 (a and b)
S
—CHF2
—H
—Br


D106 (a and b)
S
—CHF2
—H
—F


D107 (a and b)
S
—CHF2
—H
—CH3


D108 (a and b)
S
—CHF2
—H
—CF3


D109 (a and b)
S
—CHF2
—H
—OCH3


D110 (a and b)
S
—CHF2
—H
—OCH2CH3


D111 (a and b)
S
—CHF2
—H
—OCF3


D112 (a and b)
S
—CHF2
—H
-tert-butyl


D113 (a and b)
S
—CHF2
—H
-iso-propyl


D114 (a and b)
S
—OH
—Cl
—H


D115 (a and b)
S
—OH
—Br
—H


D116 (a and b)
S
—OH
—F
—H


D117 (a and b)
S
—OH
—CH3
—H


D118 (a and b)
S
—OH
—CF3
—H


D119 (a and b)
S
—OH
—OCH3
—H


D120 (a and b)
S
—OH
—OCH2CH3
—H


D121 (a and b)
S
—OH
—OCF3
—H


D122 (a and b)
S
—OH
-tert-butyl
—H


D123 (a and b)
S
—OH
-iso-propyl
—H


D124 (a and b)
S
—OH
—CH3
—CH3


D125 (a and b)
S
—OH
—H
—H


D126 (a and b)
S
—OH
—H
—Cl


D127 (a and b)
S
—OH
—H
—Br


D128 (a and b)
S
—OH
—H
—F


D129 (a and b)
S
—OH
—H
—CH3


D130 (a and b)
S
—OH
—H
—CF3


D131 (a and b)
S
—OH
—H
—OCH3


D132 (a and b)
S
—OH
—H
—OCH2CH3


D133 (a and b)
S
—OH
—H
—OCF3


D134 (a and b)
S
—OH
—H
-tert-butyl


D135 (a and b)
S
—OH
—H
-iso-propyl


D136 (a and b)
S
—NO2
—Cl
—H


D137 (a and b)
S
—NO2
—Br
—H


D138 (a and b)
S
—NO2
—F
—H


D139 (a and b)
S
—NO2
—CH3
—H


D140 (a and b)
S
—NO2
—CF3
—H


D141 (a and b)
S
—NO2
—OCH3
—H


D142 (a and b)
S
—NO2
—OCH2CH3
—H


D143 (a and b)
S
—NO2
—OCF3
—H


D144 (a and b)
S
—NO2
-tert-butyl
—H


D145 (a and b)
S
—NO2
-iso-propyl
—H


D146 (a and b)
S
—NO2
—CH3
—CH3


D147 (a and b)
S
—NO2
—H
—H


D148 (a and b)
S
—NO2
—H
—Cl


D149 (a and b)
S
—NO2
—H
—Br


D150 (a and b)
S
—NO2
—H
—F


D151 (a and b)
S
—NO2
—H
—CH3


D152 (a and b)
S
—NO2
—H
—CF3


D153 (a and b)
S
—NO2
—H
—OCH3


D154 (a and b)
S
—NO2
—H
—OCH2CH3


D155 (a and b)
S
—NO2
—H
—OCF3


D156 (a and b)
S
—NO2
—H
-tert-butyl


D157 (a and b)
S
—NO2
—H
-iso-propyl


D158 (a and b)
S
—CN
—Br
—H


D159 (a and b)
S
—CN
—Cl
—H


D160 (a and b)
S
—CN
—F
—H


D161 (a and b)
S
—CN
—CH3
—H


D162 (a and b)
S
—CN
—CF3
—H


D163 (a and b)
S
—CN
—OCH3
—H


D164 (a and b)
S
—CN
—OCH2CH3
—H


D165 (a and b)
S
—CN
—OCF3
—H


D166 (a and b)
S
—CN
-tert-butyl
—H


D167 (a and b)
S
—CN
-iso-propyl
—H


D168 (a and b)
S
—CN
—CH3
—CH3


D169 (a and b)
S
—CN
—H
—H


D170 (a and b)
S
—CN
—H
—Cl


D171 (a and b)
S
—CN
—H
—Br


D172 (a and b)
S
—CN
—H
—F


D173 (a and b)
S
—CN
—H
—CH3


D174 (a and b)
S
—CN
—H
—CF3


D175 (a and b)
S
—CN
—H
—OCH3


D176 (a and b)
S
—CN
—H
—OCH2CH3


D177 (a and b)
S
—CN
—H
—OCF3


D178 (a and b)
S
—CN
—H
-tert-butyl


D179 (a and b)
S
—CN
—H
-iso-propyl


D180 (a and b)
S
—Br
—Br
—H


D181 (a and b)
S
—Br
—Cl
—H


D182 (a and b)
S
—Br
—F
—H


D183 (a and b)
S
—Br
—CH3
—H


D184 (a and b)
S
—Br
—CF3
—H


D185 (a and b)
S
—Br
—OCH3
—H


D186 (a and b)
S
—Br
—OCH2CH3
—H


D187 (a and b)
S
—Br
—OCF3
—H


D188 (a and b)
S
—Br
-tert-butyl
—H


D189 (a and b)
S
—Br
-iso-propyl
—H


D190 (a and b)
S
—Br
—CH3
—CH3


D191 (a and b)
S
—Br
—H
—H


D192 (a and b)
S
—Br
—H
—Cl


D193 (a and b)
S
—Br
—H
—Br


D194 (a and b)
S
—Br
—H
—F


D195 (a and b)
S
—Br
—H
—CH3


D196 (a and b)
S
—Br
—H
—CF3


D197 (a and b)
S
—Br
—H
—OCH3


D198 (a and b)
S
—Br
—H
—OCH2CH3


D199 (a and b)
S
—Br
—H
—OCF3


D200 (a and b)
S
—Br
—H
-tert-butyl


D201 (a and b)
S
—Br
—H
-iso-propyl


D202 (a and b)
S
—I
—Cl
—H


D203 (a and b)
S
—I
—Br
—H


D204 (a and b)
S
—I
—F
—H


D205 (a and b)
S
—I
—CH3
—H


D206 (a and b)
S
—I
—CF3
—H


D207 (a and b)
S
—I
—OCH3
—H


D208 (a and b)
S
—I
—OCH2CH3
—H


D209 (a and b)
S
—I
—OCF3
—H


D210 (a and b)
S
—I
-tert-butyl
—H


D211 (a and b)
S
—I
-iso-propyl
—H


D212 (a and b)
S
—I
—CH3
—CH3


D213 (a and b)
S
—I
—H
—H


D214 (a and b)
S
—I
—H
—Cl


D215 (a and b)
S
—I
—H
—Br


D216 (a and b)
S
—I
—H
—F


D217 (a and b)
S
—I
—H
—CH3


D218 (a and b)
S
—I
—H
—CF3


D219 (a and b)
S
—I
—H
—OCH3


D220 (a and b)
S
—I
—H
—OCH2CH3


D221 (a and b)
S
—I
—H
—OCF3


D222 (a and b)
S
—I
—H
-tert-butyl


D223 (a and b)
S
—I
—H
-iso-propyl


D224 (a and b)
O
—H
—Cl
—H


D225 (a and b)
O
—H
—Br
—H


D226 (a and b)
O
—H
—F
—H


D227 (a and b)
O
—H
—CH3
—H


D228 (a and b)
O
—H
—CF3
—H


D229 (a and b)
O
—H
—OCH3
—H


D230 (a and b)
O
—H
—OCH2CH3
—H


D231 (a and b)
O
—H
—OCF3
—H


D232 (a and b)
O
—H
-tert-butyl
—H


D233 (a and b)
O
—H
-iso-propyl
—H


D234 (a and b)
O
—H
—CH3
—CH3


D235 (a and b)
O
—H
—H
—H


D236 (a and b)
O
—H
—H
—Cl


D237 (a and b)
O
—H
—H
—Br


D238 (a and b)
O
—H
—H
—F


D239 (a and b)
O
—H
—H
—CH3


D240 (a and b)
O
—H
—H
—CF3


D241 (a and b)
O
—H
—H
—OCH3


D242 (a and b)
O
—H
—H
—OCH2CH3


D243 (a and b)
O
—H
—H
—OCF3


D244 (a and b)
O
—H
—H
-tert-butyl


D245 (a and b)
O
—H
—H
-iso-propyl


D246 (a and b)
O
—Cl
—Cl
—H


D247 (a and b)
O
—Cl
—Br
—H


D248 (a and b)
O
—Cl
—F
—H


D249 (a and b)
O
—Cl
—CH3
—H


D250 (a and b)
O
—Cl
—CF3
—H


D251 (a and b)
O
—Cl
—OCH3
—H


D252 (a and b)
O
—Cl
—OCH2CH3
—H


D253 (a and b)
O
—Cl
—OCF3
—H


D254 (a and b)
O
—Cl
-tert-butyl
—H


D255 (a and b)
O
—Cl
-iso-propyl
—H


D256 (a and b)
O
—Cl
—CH3
—CH3


D257 (a and b)
O
—Cl
—H
—H


D258 (a and b)
O
—Cl
—H
—CH3


D259 (a and b)
O
—Cl
—H
—Cl


D260 (a and b)
O
—Cl
—H
—Br


D261 (a and b)
O
—Cl
—H
—F


D262 (a and b)
O
—Cl
—H
—CF3


D263 (a and b)
O
—Cl
—H
—OCH3


D264 (a and b)
O
—Cl
—H
—OCH2CH3


D265 (a and b)
O
—Cl
—H
—OCF3


D266 (a and b)
O
—Cl
—H
-tert-butyl


D267 (a and b)
O
—Cl
—H
-iso-propyl


D268 (a and b)
O
—Cl
—H
—OCF3


D269 (a and b)
O
—Cl
—H
-tert-butyl


D270 (a and b)
O
—Cl
—H
-iso-propyl


D271 (a and b)
O
—CH3
—Cl
—H


D272 (a and b)
O
—CH3
—Br
—H


D273 (a and b)
O
—CH3
—F
—H


D274 (a and b)
O
—CH3
—CH3
—H


D275 (a and b)
O
—CH3
—CF3
—H


D276 (a and b)
O
—CH3
—OCH3
—H


D277 (a and b)
O
—CH3
—OCH2CH3
—H


D278 (a and b)
O
—CH3
—OCF3
—H


D279 (a and b)
O
—CH3
-tert-butyl
—H


D280 (a and b)
O
—CH3
-iso-propyl
—H


D281 (a and b)
O
—CH3
—CH3
—CH3


D282 (a and b)
O
—CH3
—H
—H


D283 (a and b)
O
—CH3
—H
—Cl


D284 (a and b)
O
—CH3
—H
—Br


D285 (a and b)
O
—CH3
—H
—F


D286 (a and b)
O
—CH3
—H
—CH3


D287 (a and b)
O
—CH3
—H
—CF3


D288 (a and b)
O
—CH3
—H
—OCH3


D289 (a and b)
O
—CH3
—H
—OCH2CH3


D290 (a and b)
O
—CH3
—H
—OCF3


D291 (a and b)
O
—CH3
—H
-tert-butyl


D292 (a and b)
O
—CH3
—H
-iso-propyl


D293 (a and b)
O
—CF3
—Cl
—H


D294 (a and b)
O
—CF3
—Br
—H


D295 (a and b)
O
—CF3
—F
—II


D296 (a and b)
O
—CF3
—CH3
—H


D297 (a and b)
O
—CF3
—CF3
—H


D298 (a and b)
O
—CF3
—OCH3
—H


D299 (a and b)
O
—CF3
—OCH2CH3
—H


D300 (a and b)
O
—CF3
—OCF3
—H


D301 (a and b)
O
—CF3
-tert-butyl
—H


D302 (a and b)
O
—CF3
-iso-propyl
—H


D303 (a and b)
O
—CF3
—CH3
—CH3


D304 (a and b)
O
—CF3
—H
—H


D305 (a and b)
O
—CF3
—H
—Cl


D306 (a and b)
O
—CF3
—H
—Br


D307 (a and b)
O
—CF3
—H
—F


D308 (a and b)
O
—CF3
—H
—CH3


D309 (a and b)
O
—CF3
—H
—CF3


D310 (a and b)
O
—CF3
—H
—OCH3


D311 (a and b)
O
—CF3
—H
—OCH2CH3


D312 (a and b)
O
—CF3
—H
—OCF3


D313 (a and b)
O
—CF3
—H
-tert-butyl


D314 (a and b)
O
—CF3
—H
-iso-propyl


D315 (a and b)
O
—CHF2
—Cl
—H


D316 (a and b)
O
—CHF2
—Br
—H


D317 (a and b)
O
—CHF2
—F
—H


D318 (a and b)
O
—CHF2
—CH3
—H


D319 (a and b)
O
—CHF2
—CF3
—H


D320 (a and b)
O
—CHF2
—OCH3
—H


D321 (a and b)
O
—CHF2
—OCH2CH3
—H


D322 (a and b)
O
—CHF2
—OCF3
—H


D323 (a and b)
O
—CHF2
-tert-butyl
—H


D324 (a and b)
O
—CHF2
-iso-propyl
—H


D325 (a and b)
O
—CHF2
—CH3
—CH3


D326 (a and b)
O
—CHF2
—H
—H


D327 (a and b)
O
—CHF2
—H
—Cl


D328 (a and b)
O
—CHF2
—H
—Br


D329 (a and b)
O
—CHF2
—H
—F


D330 (a and b)
O
—CHF2
—H
—CH3


D331 (a and b)
O
—CHF2
—H
—CF3


D332 (a and b)
O
—CHF2
—H
—OCH3


D333 (a and b)
O
—CHF2
—H
—OCH2CH3


D334 (a and b)
O
—CHF2
—H
—OCF3


D335 (a and b)
O
—CHF2
—H
-tert-butyl


D336 (a and b)
O
—CHF2
—H
-iso-propyl


D337 (a and b)
O
—OH
—Cl
—H


D338 (a and b)
O
—OH
—Br
—H


D339 (a and b)
O
—OH
—F
—H


D340 (a and b)
O
—OH
—CH3
—H


D341 (a and b)
O
—OH
—CF3
—H


D342 (a and b)
O
—OH
—OCH3
—H


D343 (a and b)
O
—OH
—OCH2CH3
—H


D344 (a and b)
O
—OH
—OCF3
—H


D345 (a and b)
O
—OH
-tert-butyl
—H


D346 (a and b)
O
—OH
-iso-propyl
—H


D347 (a and b)
O
—OH
—CH3
—CH3


D348 (a and b)
O
—OH
—H
—H


D349 (a and b)
O
—OH
—H
—Cl


D350 (a and b)
O
—OH
—H
—Br


D351 (a and b)
O
—OH
—H
—F


D352 (a and b)
O
—OH
—H
—CH3


D353 (a and b)
O
—OH
—H
—CF3


D354 (a and b)
O
—OH
—H
—OCH3


D355 (a and b)
O
—OH
—H
—OCH2CH3


D356 (a and b)
O
—OH
—H
—OCF3


D357 (a and b)
O
—OH
—H
-tert-butyl


D358 (a and b)
O
—OH
—H
-iso-propyl


D359 (a and b)
O
—NO2
—Cl
—H


D360 (a and b)
O
—NO2
—Br
—H


D361 (a and b)
O
—NO2
—F
—H


D362 (a and b)
O
—NO2
—CH3
—H


D363 (a and b)
O
—NO2
—CF3
—H


D364 (a and b)
O
—NO2
—OCH3
—H


D365 (a and b)
O
—NO2
—OCH2CH3
—H


D366 (a and b)
O
—NO2
—OCF3
—H


D367 (a and b)
O
—NO2
-tert-butyl
—H


D368 (a and b)
O
—NO2
-iso-propyl
—H


D369 (a and b)
O
—NO2
—CH3
—CH3


D370 (a and b)
O
—NO2
—H
—H


D371 (a and b)
O
—NO2
—H
—Cl


D372 (a and b)
O
—NO2
—H
—Br


D373 (a and b)
O
—NO2
—H
—F


D374 (a and b)
O
—NO2
—H
—CH3


D375 (a and b)
O
—NO2
—H
—CF3


D376 (a and b)
O
—NO2
—H
—OCH3


D377 (a and b)
O
—NO2
—H
—OCH2CH3


D378 (a and b)
O
—NO2
—H
—OCF3


D379 (a and b)
O
—NO2
—H
-tert-butyl


D380 (a and b)
O
—NO2
—H
-iso-propyl


D381 (a and b)
O
—CN
—Br
—H


D382 (a and b)
O
—CN
—Cl
—H


D383 (a and b)
O
—CN
—F
—H


D384 (a and b)
O
—CN
—CH3
—H


D385 (a and b)
O
—CN
—CF3
—H


D386 (a and b)
O
—CN
—OCH3
—H


D387 (a and b)
O
—CN
—OCH2CH3
—H


D388 (a and b)
O
—CN
—OCF3
—H


D389 (a and b)
O
—CN
-tert-butyl
—H


D390 (a and b)
O
—CN
-iso-propyl
—H


D391 (a and b)
O
—CN
—CH3
—CH3


D392 (a and b)
O
—CN
—H
—H


D393 (a and b)
O
—CN
—H
—Cl


D394 (a and b)
O
—CN
—H
—Br


D395 (a and b)
O
—CN
—H
—F


D396 (a and b)
O
—CN
—H
—CH3


D397 (a and b)
O
—CN
—H
—CF3


D398 (a and b)
O
—CN
—H
—OCH3


D399 (a and b)
O
—CN
—H
—OCH2CH3


D400 (a and b)
O
—CN
—H
—OCF3


D401 (a and b)
O
—CN
—H
-tert-butyl


D402 (a and b)
O
—CN
—H
-iso-propyl


D403 (a and b)
O
—Br
—Br
—H


D404 (a and b)
O
—Br
—Cl
—H


D405 (a and b)
O
—Br
—F
—H


D406 (a and b)
O
—Br
—CH3
—H


D407 (a and b)
O
—Br
—CF3
—H


D408 (a and b)
O
—Br
—OCH3
—H


D409 (a and b)
O
—Br
—OCH2CH3
—H


D410 (a and b)
O
—Br
—OCF3
—H


D411 (a and b)
O
—Br
-tert-butyl
—H


D412 (a and b)
O
—Br
-iso-propyl
—H


D413 (a and b)
O
—Br
—CH3
—CH3


D414 (a and b)
O
—Br
—H
—H


D415 (a and b)
O
—Br
—H
—Cl


D416 (a and b)
O
—Br
—H
—Br


D417 (a and b)
O
—Br
—H
—F


D418 (a and b)
O
—Br
—H
—CH3


D419 (a and b)
O
—Br
—H
—CF3


D420 (a and b)
O
—Br
—H
—OCH3


D421 (a and b)
O
—Br
—H
—OCH2CH3


D422 (a and b)
O
—Br
—H
—OCF3


D423 (a and b)
O
—Br
—H
-tert-butyl


D424 (a and b)
O
—Br
—H
-iso-propyl


D425 (a and b)
O
—I
—Cl
—H


D426 (a and b)
O
—I
—Br
—H


D427 (a and b)
O
—I
—F
—H


D428 (a and b)
O
—I
—CH3
—H


D429 (a and b)
O
—I
—CF3
—H


D430 (a and b)
O
—I
—OCH3
—H


D431 (a and b)
O
—I
—OCH2CH3
—H


D432 (a and b)
O
—I
—OCF3
—H


D433 (a and b)
O
—I
-tert-butyl
—H


D434 (a and b)
O
—I
-iso-propyl
—H


D435 (a and b)
O
—I
—CH3
—CH3


D436 (a and b)
O
—I
—H
—H


D437 (a and b)
O
—I
—H
—Cl


D438 (a and b)
O
—I
—H
—Br


D439 (a and b)
O
—I
—H
—F


D440 (a and b)
O
—I
—H
—CH3


D441 (a and b)
O
—I
—H
—CF3


D442 (a and b)
O
—I
—H
—OCH3


D443 (a and b)
O
—I
—H
—OCH2CH3


D444 (a and b)
O
—I
—H
—OCF3


D445 (a and b)
O
—I
—H
-tert-butyl


D446 (a and b)
O
—I
—H
-iso-propyl


D447 (a and b)
NH
—H
—Cl
—H


D448 (a and b)
NH
—H
—Br
—H


D449 (a and b)
NH
—H
—F
—H


D450 (a and b)
NH
—H
—CH3
—H


D451 (a and b)
NH
—H
—CF3
—H


D452 (a and b)
NH
—H
—OCH3
—H


D453 (a and b)
NH
—H
—OCH2CH3
—H


D454 (a and b)
NH
—H
—OCF3
—H


D455 (a and b)
NH
—H
-tert-butyl
—H


D456 (a and b)
NH
—H
-iso-propyl
—H


D457 (a and b)
NH
—H
—CH3
—CH3


D458 (a and b)
NH
—H
—H
—H


D459 (a and b)
NH
—H
—H
—Cl


D460 (a and b)
NH
—H
—H
—Br


D461 (a and b)
NH
—H
—H
—F


D462 (a and b)
NH
—H
—H
—CH3


D463 (a and b)
NH
—H
—H
—CF3


D464 (a and b)
NH
—H
—H
—OCH3


D465 (a and b)
NH
—H
—H
—OCH2CH3


D466 (a and b)
NH
—H
—H
—OCF3


D467 (a and b)
NH
—H
—H
-tert-butyl


D468 (a and b)
NH
—H
—H
-iso-propyl


D469 (a and b)
NH
—Cl
—Cl
—H


D470 (a and b)
NH
—Cl
—Br
—H


D471 (a and b)
NH
—Cl
—F
—H


D472 (a and b)
NH
—Cl
—CH3
—H


D473 (a and b)
NH
—Cl
—CF3
—H


D474 (a and b)
NH
—Cl
—OCH3
—H


D475 (a and b)
NH
—Cl
—OCH2CH3
—H


D476 (a and b)
NH
—Cl
—OCF3
—H


D477 (a and b)
NH
—Cl
-tert-butyl
—H


D478 (a and b)
NH
—Cl
-iso-propyl
—H


D479 (a and b)
NH
—Cl
—CH3
—CH3


D480 (a and b)
NH
—Cl
—H
—H


D481 (a and b)
NH
—Cl
—H
—Cl


D482 (a and b)
NH
—Cl
—H
—Br


D483 (a and b)
NH
—Cl
—H
—F


D484 (a and b)
NH
—Cl
—H
—CH3


D485 (a and b)
NH
—Cl
—H
—CF3


D486 (a and b)
NH
—Cl
—H
—OCH3


D487 (a and b)
NH
—Cl
—H
—OCH2CH3


D488 (a and b)
NH
—Cl
—H
—OCF3


D489 (a and b)
NH
—Cl
—H
-tert-butyl


D490 (a and b)
NH
—Cl
—H
-iso-propyl


D491 (a and b)
NH
—Cl
—H
—OCF3


D492 (a and b)
NH
—Cl
—H
-tert-butyl


D493 (a and b)
NH
—Cl
—H
-iso-propyl


D494 (a and b)
NH
—CH3
—Cl
—H


D495 (a and b)
NH
—CH3
—Br
—H


D496 (a and b)
NH
—CH3
—F
—H


D497 (a and b)
NH
—CH3
—CH3
—H


D498 (a and b)
NH
—CH3
—CF3
—H


D499 (a and b)
NH
—CH3
—OCH3
—H


D500 (a and b)
NH
—CH3
—OCH2CH3
—H


D501 (a and b)
NH
—CH3
—OCF3
—H


D502 (a and b)
NH
—CH3
-tert-butyl
—H


D503 (a and b)
NH
—CH3
-iso-propyl
—H


D504 (a and b)
NH
—CH3
—CH3
—CH3


D505 (a and b)
NH
—CH3
—H
—H


D506 (a and b)
NH
—CH3
—H
—Cl


D507 (a and b)
NH
—CH3
—H
—Br


D508 (a and b)
NH
—CH3
—H
—F


D509 (a and b)
NH
—CH3
—H
—CH3


D510 (a and b)
NH
—CH3
—H
—CF3


D511 (a and b)
NH
—CH3
—H
—OCH3


D512 (a and b)
NH
—CH3
—H
—OCH2CH3


D513 (a and b)
NH
—CH3
—H
—OCF3


D514 (a and b)
NH
—CH3
—H
-tert-butyl


D515 (a and b)
NH
—CH3
—H
-iso-propyl


D516 (a and b)
NH
—CF3
—Cl
—H


D517 (a and b)
NH
—CF3
—Br
—H


D518 (a and b)
NH
—CF3
—F
—H


D519 (a and b)
NH
—CF3
—CH3
—H


D520 (a and b)
NH
—CF3
—CF3
—H


D521 (a and b)
NH
—CF3
—OCH3
—H


D522 (a and b)
NH
—CF3
—OCH2CH3
—H


D523 (a and b)
NH
—CF3
—OCF3
—H


D524 (a and b)
NH
—CF3
-tert-butyl
—H


D525 (a and b)
NH
—CF3
-iso-propyl
—H


D526 (a and b)
NH
—CF3
—CH3
—CH3


D527 (a and b)
NH
—CF3
—H
—H


D528 (a and b)
NH
—CF3
—H
—Cl


D529 (a and b)
NH
—CF3
—H
—Br


D530 (a and b)
NH
—CF3
—H
—F


D531 (a and b)
NH
—CF3
—H
—CH3


D532 (a and b)
NH
—CF3
—H
—CF3


D533 (a and b)
NH
—CF3
—H
—OCH3


D534 (a and b)
NH
—CF3
—H
—OCH2CH3


D535 (a and b)
NH
—CF3
—H
—OCF3


D536 (a and b)
NH
—CF3
—H
-tert-butyl


D537 (a and b)
NH
—CF3
—H
-iso-propyl


D538 (a and b)
NH
—CHF2
—Cl
—H


D539 (a and b)
NH
—CHF2
—Br
—H


D540 (a and b)
NH
—CHF2
—F
—H


D541 (a and b)
NH
—CHF2
—CH3
—H


D542 (a and b)
NH
—CHF2
—CF3
—H


D543 (a and b)
NH
—CHF2
—OCH3
—H


D544 (a and b)
NH
—CHF2
—OCH2CH3
—H


D545 (a and b)
NH
—CHF2
—OCF3
—H


D546 (a and b)
NH
—CHF2
-tert-butyl
—H


D547 (a and b)
NH
—CHF2
-iso-propyl
—H


D548 (a and b)
NH
—CHF2
—CH3
—CH3


D549 (a and b)
NH
—CHF2
—H
—H


D550 (a and b)
NH
—CHF2
—H
—Cl


D551 (a and b)
NH
—CHF2
—H
—Br


D552 (a and b)
NH
—CHF2
—H
—F


D553 (a and b)
NH
—CHF2
—H
—CH3


D554 (a and b)
NH
—CHF2
—H
—CF3


D555 (a and b)
NH
—CHF2
—H
—OCH3


D556 (a and b)
NH
—CHF2
—H
—OCH2CH3


D557 (a and b)
NH
—CHF2
—H
—OCF3


D558 (a and b)
NH
—CHF2
—H
-tert-butyl


D559 (a and b)
NH
—CHF2
—H
-iso-propyl


D560 (a and b)
NH
—OH
—Cl
—H


D561 (a and b)
NH
—OH
—Br
—H


D562 (a and b)
NH
—OH
—F
—H


D563 (a and b)
NH
—OH
—CH3
—H


D564 (a and b)
NH
—OH
—CF3
—H


D565 (a and b)
NH
—OH
—OCH3
—H


D566 (a and b)
NH
—OH
—OCH2CH3
—H


D567 (a and b)
NH
—OH
—OCF3
—H


D568 (a and b)
NH
—OH
-tert-butyl
—H


D569 (a and b)
NH
—OH
-iso-propyl
—H


D570 (a and b)
NH
—OH
—CH3
—CH3


D571 (a and b)
NH
—OH
—H
—H


D572 (a and b)
NH
—OH
—H
—Cl


D573 (a and b)
NH
—OH
—H
—Br


D574 (a and b)
NH
—OH
—H
—F


D575 (a and b)
NH
—OH
—H
—CH3


D576 (a and b)
NH
—OH
—H
—CF3


D577 (a and b)
NH
—OH
—H
—OCH3


D578 (a and b)
NH
—OH
—H
—OCH2CH3


D579 (a and b)
NH
—OH
—H
—OCF3


D580 (a and b)
NH
—OH
—H
-tert-butyl


D581 (a and b)
NH
—OH
—H
-iso-propyl


D582 (a and b)
NH
—NO2
—Cl
—H


D583 (a and b)
NH
—NO2
—Br
—H


D584 (a and b)
NH
—NO2
—F
—H


D585 (a and b)
NH
—NO2
—CH3
—H


DS86 (a and b)
NH
—NO2
—CF3
—H


D587 (a and b)
NH
—NO2
—OCH3
—H


D588 (a and b)
NH
—NO2
—OCH2CH3
—H


D589 (a and b)
NH
—NO2
—OCF3
—H


D590 (a and b)
NH
—NO2
-tert-butyl
—H


D591 (a and b)
NH
—NO2
-iso-propyl
—H


D592 (a and b)
NH
—NO2
—CH3
—CH3


D593 (a and b)
NH
—NO2
—H
—H


D594 (a and b)
NH
—NO2
—H
—Cl


D595 (a and b)
NH
—NO2
—H
—Br


D596 (a and b)
NH
—NO2
—H
—F


D597 (a and b)
NH
—NO2
—H
—CH3


D598 (a and b)
NH
—NO2
—H
—CF3


D599 (a and b)
NH
—NO2
—H
—OCH3


D600 (a and b)
NH
—NO2
—H
—OCH2CH3


D601 (a and b)
NH
—NO2
—H
—OCF3


D602 (a and b)
NH
—NO2
—H
-tert-butyl


D603 (a and b)
NH
—NO2
—H
-iso-propyl


D604 (a and b)
NH
—CN
—Br
—H


D605 (a and b)
NH
—CN
—Cl
—H


D606 (a and b)
NH
—CN
—F
—H


D607 (a and b)
NH
—CN
—CH3
—H


D608 (a and b)
NH
—CN
—CF3
—H


D609 (a and b)
NH
—CN
—OCH3
—H


D610 (a and b)
NH
—CN
—OCH2CH3
—H


D611 (a and b)
NH
—CN
—OCF3
—H


D612 (a and b)
NH
—CN
-tert-butyl
—H


D613 (a and b)
NH
—CN
-iso-propyl
—H


D614 (a and b)
NH
—CN
—CH3
—CH3


D615 (a and b)
NH
—CN
—H
—H


D616 (a and b)
NH
—CN
—H
—Cl


D617 (a and b)
NH
—CN
—H
—Br


D618 (a and b)
NH
—CN
—H
—F


D619 (a and b)
NH
—CN
—H
—CH3


D620 (a and b)
NH
—CN
—H
—CF3


D621 (a and b)
NH
—CN
—H
—OCH3


D622 (a and b)
NH
—CN
—H
—OCH2CH3


D623 (a and b)
NH
—CN
—H
—OCF3


D624 (a and b)
NH
—CN
—H
-tert-butyl


D625 (a and b)
NH
—CN
—H
-iso-propyl


D626 (a and b)
NH
—Br
—Br
—H


D627 (a and b)
NH
—Br
—Cl
—H


D628 (a and b)
NH
—Br
—F
—H


D629 (a and b)
NH
—Br
—CH3
—H


D630 (a and b)
NH
—Br
—CF3
—H


D631 (a and b)
NH
—Br
—OCH3
—H


D632 (a and b)
NH
—Br
—OCH2CH3
—H


D633 (a and b)
NH
—Br
—OCF3
—H


D634 (a and b)
NH
—Br
-tert-butyl
—H


D635 (a and b)
NH
—Br
-iso-propyl
—H


D636 (a and b)
NH
—Br
—CH3
—CH3


D637 (a and b)
NH
—Br
—H
—H


D638 (a and b)
NH
—Br
—H
—Cl


D639 (a and b)
NH
—Br
—H
—Br


D640 (a and b)
NH
—Br
—H
—F


D641 (a and b)
NH
—Br
—H
—CH3


D642 (a and b)
NH
—Br
—H
—CF3


D643 (a and b)
NH
—Br
—H
—OCH3


D644 (a and b)
NH
—Br
—H
—OCH2CH3


D645 (a and b)
NH
—Br
—H
—OCF3


D646 (a and b)
NH
—Br
—H
-tert-butyl


D647 (a and b)
NH
—Br
—H
-iso-propyl


D648 (a and b)
NH
—I
—Cl
—H


D649 (a and b)
NH
—I
—Br
—H


D650 (a and b)
NH
—I
—F
—H


D651 (a and b)
NH
—I
—CH3
—H


D652 (a and b)
NH
—I
—CF3
—H


D653 (a and b)
NH
—I
—OCH3
—H


D654 (a and b)
NH
—I
—OCH2CH3
—H


D655 (a and b)
NH
—I
—OCF3
—H


D656 (a and b)
NH
—I
-tert-butyl
—H


D657 (a and b)
NH
—I
-iso-propyl
—H


D658 (a and b)
NH
—I
—CH3
—CH3


D659 (a and b)
NH
—I
—H
—H


D660 (a and b)
NH
—I
—H
—Cl


D661 (a and b)
NH
—I
—H
—Br


D662 (a and b)
NH
—I
—H
—F


D663 (a and b)
NH
—I
—H
—CH3


D664 (a and b)
NH
—I
—H
—CF3


D665 (a and b)
NH
—I
—H
—OCH3


D666 (a and b)
NH
—I
—H
—OCH2CH3


D667 (a and b)
NH
—I
—H
—OCF3


D668 (a and b)
NH
—I
—H
-tert-butyl


D669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 5








(Ie)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






E01 (a and b)
—H
—H



E02 (a and b)
—H
-tert-butyl



E03 (a and b)
—H
-iso-butyl



E04 (a and b)
—H
-sec-butyl



E05 (a and b)
—H
-iso-propyl



E06 (a and b)
—H
-n-propyl



E07 (a and b)
—H
-cyclohexyl



E08 (a and b)
—H
-tert-butoxy



E09 (a and b)
—H
-isopropoxy



E10 (a and b)
—H
—CF3



E11 (a and b)
—H
—CH2CF3



E12 (a and b)
—H
—OCF3



E13 (a and b)
—H
—Cl



E14 (a and b)
—H
—Br



E15 (a and b)
—H
—I



E16 (a and b)
—H
-n-butyl



E17 (a and b)
—H
—CH3



E18 (a and b)
—H
—SCF3



E19 (a and b)
—H
—N(CH2CH3)2



E20 (a and b)
—H
—OCF2CHF2



E21 (a and b)
—H
—C(OH)(CF3)2



E22 (a and b)
—H
-(1,1-dimethyl-pentyl)



E23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



E24 (a and b)
—H
—N-piperidinyl



E25 (a and b)
—Cl
—H



E26 (a and b)
—Cl
-tert-butyl



E27 (a and b)
—Cl
-iso-butyl



E28 (a and b)
—Cl
-sec-butyl



E29 (a and b)
—Cl
-iso-propyl



E30 (a and b)
—Cl
-n-propyl



E31 (a and b)
—Cl
-cyclohexyl



E32 (a and b)
—Cl
-tert-butoxy



E33 (a and b)
—Cl
-isopropoxy



E34 (a and b)
—Cl
—CF3



E35 (a and b)
—Cl
—CH2CF3



E36 (a and b)
—Cl
—OCF3



E37 (a and b)
—Cl
—Cl



E38 (a and b)
—Cl
—Br



E39 (a and b)
—Cl
—I



E40 (a and b)
—Cl
-n-butyl



E41 (a and b)
—Cl
—CH3



E42 (a and b)
—Cl
—SCF3



E43 (a and b)
—Cl
—N(CH2CH3)2



E44 (a and b)
—Cl
—OCF2CHF2



E45 (a and b)
—Cl
—C(OH)(CF3)2



E46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



E47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



E48 (a and b)
—Cl
—N-piperidinyl



E49 (a and b)
—F
—H



E50 (a and b)
—F
-tert-butyl



E51 (a and b)
—F
-iso-butyl



E52 (a and b)
—F
-sec-butyl



E53 (a and b)
—F
-iso-propyl



E54 (a and b)
—F
-n-propyl



E55 (a and b)
—F
-cyclohexyl



E56 (a and b)
—F
-tert-butoxy



E57 (a and b)
—F
-isopropoxy



E58 (a and b)
—F
—CF3



E59 (a and b)
—F
—CH2CF3



E60 (a and b)
—F
—OCF3



E61 (a and b)
—F
—Cl



E62 (a and b)
—F
—Br



E63 (a and b)
—F
—I



E64 (a and b)
—F
-n-butyl



E65 (a and b)
—F
—CH3



E66 (a and b)
—F
—SCF3



E67 (a and b)
—F
—N(CH2CH3)2



E68 (a and b)
—F
—OCF2CHF2



E69 (a and b)
—F
—C(OH)(CF3)2



E70 (a and b)
—F
-(1,1-dimethyl-pentyl)



E71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



E72 (a and b)
—F
—N-piperidinyl



E73 (a and b)
—CH3
—H



E74 (a and b)
—CH3
-iso-butyl



E75 (a and b)
—CH3
-tert-butyl



E76 (a and b)
—CH3
-sec-butyl



E77 (a and b)
—CH3
-iso-propyl



E78 (a and b)
—CH3
-n-propyl



E79 (a and b)
—CH3
-cyclohexyl



E80 (a and b)
—CH3
-tert-butoxy



E81 (a and b)
—CH3
-isopropoxy



E82 (a and b)
—CH3
—CF3



E83 (a and b)
—CH3
—CH2CF3



E84 (a and b)
—CH3
—OCF3



E85 (a and b)
—CH3
—Cl



E86 (a and b)
—CH3
—Br



E87 (a and b)
—CH3
—I



E88 (a and b)
—CH3
-n-butyl



E89 (a and b)
—CH3
—CH3



E90 (a and b)
—CH3
—SCF3



E91 (a and b)
—CH3
—N(CH2CH3)2



E92 (a and b)
—CH3
—OCF2CHF2



E93 (a and b)
—CH3
—C(OH)(CF3)2



E94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



E95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



E96 (a and b)
—CH3
—N-piperidinyl



E97 (a and b)
—CF3
—H



E98 (a and b)
—CF3
-tert-butyl



E99 (a and b)
—CF3
-iso-butyl



E100 (a and b)
—CF3
-sec-butyl



E101 (a and b)
—CF3
-iso-propyl



E102 (a and b)
—CF3
-n-propyl



E103 (a and b)
—CF3
-cyclohexyl



E104 (a and b)
—CF3
-tert-butoxy



E105 (a and b)
—CF3
-isopropoxy



E106 (a and b)
—CF3
—CF3



E107 (a and b)
—CF3
—CH2CF3



E108 (a and b)
—CF3
—OCF3



E109 (a and b)
—CF3
—Cl



E110 (a and b)
—CF3
—Br



E111 (a and b)
—CF3
—I



E112 (a and b)
—CF3
-n-butyl



E113 (a and b)
—CF3
—CH3



E114 (a and b)
—CF3
—SCF3



E115 (a and b)
—CF3
—N(CH2CH3)2



E116 (a and b)
—CF3
—OCF2CHF2



E117 (a and b)
—CF3
—C(OH)(CF3)2



E118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



E119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



E120 (a and b)
—CF3
—N-piperidinyl



E121 (a and b)
—CHF2
-tert-butyl



E122 (a and b)
—CHF2
—H



E123 (a and b)
—CHF2
-iso-butyl



E124 (a and b)
—CHF2
-sec-butyl



E125 (a and b)
—CHF2
-iso-propyl



E126 (a and b)
—CHF2
-n-propyl



E127 (a and b)
—CHF2
-cyclohexyl



E128 (a and b)
—CHF2
-tert-butoxy



E129 (a and b)
—CHF2
-isopropoxy



E130 (a and b)
—CHF2
—CF3



E131 (a and b)
—CHF2
—CH2CF3



E132 (a and b)
—CHF2
—OCF3



E133 (a and b)
—CHF2
—Cl



E134 (a and b)
—CHF2
—Br



E135 (a and b)
—CHF2
—I



E136 (a and b)
—CHF2
-n-butyl



E137 (a and b)
—CHF2
—CH3



E138 (a and b)
—CHF2
—SCF3



E139 (a and b)
—CHF2
—N(CH2CH3)2



E140 (a and b)
—CHF2
—OCF2CHF2



E141 (a and b)
—CHF2
—C(OH)(CF3)2



E142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



E143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



E144 (a and b)
—CHF2
—N-piperidinyl



E145 (a and b)
—OH
—H



E146 (a and b)
—OH
-tert-butyl



E147 (a and b)
—OH
-iso-butyl



E148 (a and b)
—OH
-sec-butyl



E149 (a and b)
—OH
-iso-propyl



E150 (a and b)
—OH
-n-propyl



E151 (a and b)
—OH
-cyclohexyl



E152 (a and b)
—OH
-tert-butoxy



E153 (a and b)
—OH
-isopropoxy



E154 (a and b)
—OH
—CF3



E155 (a and b)
—OH
—CH2CF3



E156 (a and b)
—OH
—OCF3



E157 (a and b)
—OH
—Cl



E158 (a and b)
—OH
—Br



E159 (a and b)
—OH
—I



E160 (a and b)
—OH
-n-butyl



E161 (a and b)
—OH
—CH3



E162 (a and b)
—OH
—SCF3



E163 (a and b)
—OH
—N(CH2CH3)2



E164 (a and b)
—OH
—OCF2CHF2



E165 (a and b)
—OH
—C(OH)(CF3)2



E166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



E167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



E168 (a and b)
—OH
—N-piperidinyl



E169 (a and b)
—NO2
—H



E170 (a and b)
—NO2
-tert-butyl



E171 (a and b)
—NO2
-iso-butyl



E172 (a and b)
—NO2
-sec-butyl



E173 (a and b)
—NO2
-iso-propyl



E174 (a and b)
—NO2
-n-propyl



E175 (a and b)
—NO2
-cyclohexyl



E176 (a and b)
—NO2
-tert-butoxy



E177 (a and b)
—NO2
-isopropoxy



E178 (a and b)
—NO2
—CF3



E179 (a and b)
—NO2
—CH2CF3



E180 (a and b)
—NO2
—OCF3



E181 (a and b)
—NO2
—Cl



E182 (a and b)
—NO2
—Br



E183 (a and b)
—NO2
—I



E184 (a and b)
—NO2
-n-butyl



E185 (a and b)
—NO2
—CH3



E186 (a and b)
—NO2
—SCF3



E187 (a and b)
—NO2
—N(CH2CH3)2



E188 (a and b)
—NO2
—OCF2CHF2



E189 (a and b)
—NO2
—C(OH)(CF3)2



E190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



E191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



E192 (a and b)
—NO2
—N-piperidinyl



E193 (a and b)
—CN
—H



E194 (a and b)
—CN
-tert-butyl



E195 (a and b)
—CN
-iso-butyl



E196 (a and b)
—CN
-sec-butyl



E197 (a and b)
—CN
-iso-propyl



E198 (a and b)
—CN
-n-propyl



E199 (a and b)
—CN
-cyclohexyl



E200 (a and b)
—CN
-tert-butoxy



E201 (a and b)
—CN
-isopropoxy



E202 (a and b)
—CN
—CF3



E203 (a and b)
—CN
—CH2CF3



E204 (a and b)
—CN
—OCF3



E205 (a and b)
—CN
—Cl



E206 (a and b)
—CN
—Br



E207 (a and b)
—CN
—I



E208 (a and b)
—CN
-n-butyl



E209 (a and b)
—CN
—CH3



E210 (a and b)
—CN
—SCF3



E211 (a and b)
—CN
—N(CH2CH3)2



E212 (a and b)
—CN
—OCF2CHF2



E213 (a and b)
—CN
—C(OH)(CF3)2



E214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



E215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



E216 (a and b)
—CN
—N-piperidinyl



E217 (a and b)
—Br
—H



E218 (a and b)
—Br
-tert-butyl



E219 (a and b)
—Br
-iso-butyl



E220 (a and b)
—Br
-sec-butyl



E221 (a and b)
—Br
-iso-propyl



E222 (a and b)
—Br
-n-propyl



E223 (a and b)
—Br
-cyclohexyl



E224 (a and b)
—Br
-tert-butoxy



E225 (a and b)
—Br
-isopropoxy



E226 (a and b)
—Br
—CF3



E227 (a and b)
—Br
—CH2CF3



E228 (a and b)
—Br
—OCF3



E229 (a and b)
—Br
—Cl



E230 (a and b)
—Br
—Br



E231 (a and b)
—Br
—I



E232 (a and b)
—Br
-n-butyl



E233 (a and b)
—Br
—CH3



E234 (a and b)
—Br
—SCF3



E235 (a and b)
—Br
—N(CH2CH3)2



E236 (a and b)
—Br
—OCF2CHF2



E237 (a and b)
—Br
—C(OH)(CF3)2



E238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



E239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



E240 (a and b)
—Br
—N-piperidinyl



E241 (a and b)
—I
-tert-butyl



E242 (a and b)
—I
—H



E243 (a and b)
—I
-iso-butyl



E244 (a and b)
—I
-sec-butyl



E245 (a and b)
—I
-iso-propyl



E246 (a and b)
—I
-n-propyl



E247 (a and b)
—I
-cyclohexyl



E248 (a and b)
—I
-tert-butoxy



E249 (a and b)
—I
-isopropoxy



E250 (a and b)
—I
—CF3



E251 (a and b)
—I
—CH2CF3



E252 (a and b)
—I
—OCF3



E253 (a and b)
—I
—Cl



E254 (a and b)
—I
—Br



E255 (a and b)
—I
—I



E256 (a and b)
—I
-n-butyl



E257 (a and b)
—I
—CH3



E258 (a and b)
—I
—SCF3



E259 (a and b)
—I
—N(CH2CH3)2



E260 (a and b)
—I
—OCF2CHF2



E261 (a and b)
—I
—C(OH)(CF3)2



E262 (a and b)
—I
-(1,1-dimethyl-pentyl)



E263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



E264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 6








(If)









embedded image







and pharmaceutically acceptable salts thereof, wherein:











Compound
Y
R1
(R8)a
(R8)b





F01 (a and b)
S
—H
—Cl
—H


F02 (a and b)
S
—H
—Br
—H


F03 (a and b)
S
—H
—F
—H


F04 (a and b)
S
—H
—CH3
—H


F05 (a and b)
S
—H
—CF3
—H


F06 (a and b)
S
—H
—OCH3
—H


F07 (a and b)
S
—H
—OCH2CH3
—H


F08 (a and b)
S
—H
—OCF3
—H


F09 (a and b)
S
—H
-tert-butyl
—H


F10 (a and b)
S
—H
-iso-propyl
—H


F11 (a and b)
S
—H
—CH3
—CH3


F12 (a and b)
S
—H
—H
—H


F13 (a and b)
S
—H
—H
—Cl


F14 (a and b)
S
—H
—H
—Br


F15 (a and b)
S
—H
—H
—F


F16 (a and b)
S
—H
—H
—CH3


F17 (a and b)
S
—H
—H
—CF3


F18 (a and b)
S
—H
—H
—OCH3


F19 (a and b)
S
—H
—H
—OCH2CH3


F20 (a and b)
S
—H
—H
—OCF3


F21 (a and b)
S
—H
—H
-tert-butyl


F22 (a and b)
S
—H
—H
-iso-propyl


F23 (a and b)
S
—Cl
—Cl
—H


F24 (a and b)
S
—Cl
—Br
—H


F25 (a and b)
S
—Cl
—F
—H


F26 (a and b)
S
—Cl
—CH3
—H


F27 (a and b)
S
—Cl
—CF3
—H


F28 (a and b)
S
—Cl
—OCH3
—H


F29 (a and b)
S
—Cl
—OCH2CH3
—H


F30 (a and b)
S
—Cl
—OCF3
—H


F31 (a and b)
S
—Cl
-tert-butyl
—H


F32 (a and b)
S
—Cl
-iso-propyl
—H


F33 (a and b)
S
—Cl
—CH3
—CH3


F34 (a and b)
S
—Cl
—H
—H


F35 (a and b)
S
—Cl
—H
—Cl


F36 (a and b)
S
—Cl
—H
—Br


F37 (a and b)
S
—Cl
—H
—F


F38 (a and b)
S
—Cl
—H
—CH3


F39 (a and b)
S
—Cl
—H
—CF3


F40 (a and b)
S
—Cl
—H
—OCH3


F41 (a and b)
S
—Cl
—H
—OCH2CH3


F42 (a and b)
S
—Cl
—H
—OCF3


F43 (a and b)
S
—Cl
—H
-tert-butyl


F44 (a and b)
S
—Cl
—H
-iso-propyl


F45 (a and b)
S
—Cl
—H
—OCF3


F46 (a and b)
S
—Cl
—H
-tert-butyl


F47 (a and b)
S
—Cl
—H
-iso-propyl


F48 (a and b)
S
—CH3
—Cl
—H


F49 (a and b)
S
—CH3
—Br
—H


F50 (a and b)
S
—CH3
—F
—H


F51 (a and b)
S
—CH3
—CH3
—H


F52 (a and b)
S
—CH3
—CF3
—H


F53 (a and b)
S
—CH3
—OCH3
—H


F54 (a and b)
S
—CH3
—OCH2CH3
—H


F55 (a and b)
S
—CH3
—OCF3
—H


F56 (a and b)
S
—CH3
-tert-butyl
—H


F57 (a and b)
S
—CH3
-iso-propyl
—H


F58 (a and b)
S
—CH3
—CH3
—CH3


F59 (a and b)
S
—CH3
—H
—H


F60 (a and b)
S
—CH3
—H
—Cl


F61 (a and b)
S
—CH3
—H
—Br


F62 (a and b)
S
—CH3
—H
—F


F63 (a and b)
S
—CH3
—H
—CH3


F64 (a and b)
S
—CH3
—H
—CF3


F65 (a and b)
S
—CH3
—H
—OCH3


F66 (a and b)
S
—CH3
—H
—OCH2CH3


F67 (a and b)
S
—CH3
—H
—OCF3


F68 (a and b)
S
—CH3
—H
-tert-butyl


F69 (a and b)
S
—CH3
—H
-iso-propyl


F70 (a and b)
S
—CF3
—Cl
—H


F71 (a and b)
S
—CF3
—Br
—H


F72 (a and b)
S
—CF3
—F
—H


F73 (a and b)
S
—CF3
—CH3
—H


F74 (a and b)
S
—CF3
—CF3
—H


F75 (a and b)
S
—CF3
—OCH3
—H


F76 (a and b)
S
—CF3
—OCH2CH3
—H


F77 (a and b)
S
—CF3
—OCF3
—H


F78 (a and b)
S
—CF3
-tert-butyl
—H


F79 (a and b)
S
—CF3
-iso-propyl
—H


F80 (a and b)
S
—CF3
—CH3
—CH3


F81 (a and b)
S
—CF3
—H
—H


F82 (a and b)
S
—CF3
—H
—Cl


F83 (a and b)
S
—CF3
—H
—Br


F84 (a and b)
S
—CF3
—H
—F


F85 (a and b)
S
—CF3
—H
—CH3


F86 (a and b)
S
—CF3
—H
—CF3


F87 (a and b)
S
—CF3
—H
—OCH3


F88 (a and b)
S
—CF3
—H
—OCH2CH3


F89 (a and b)
S
—CF3
—H
—OCF3


F90 (a and b)
S
—CF3
—H
-tert-butyl


F91 (a and b)
S
—CF3
—H
-iso-propyl


F92 (a and b)
S
—CHF2
—Cl
—H


F93 (a and b)
S
—CHF2
—Br
—H


F94 (a and b)
S
—CHF2
—F
—H


F95 (a and b)
S
—CHF2
—CH3
—H


F96 (a and b)
S
—CHF2
—CF3
—H


F97 (a and b)
S
—CHF2
—OCH3
—H


F98 (a and b)
S
—CHF2
—OCH2CH3
—H


F99 (a and b)
S
—CHF2
—OCF3
—H


F100 (a and b)
S
—CHF2
-tert-butyl
—H


F101 (a and b)
S
—CHF2
-iso-propyl
—H


F102 (a and b)
S
—CHF2
—CH3
—CH3


F103 (a and b)
S
—CHF2
—H
—H


F104 (a and b)
S
—CHF2
—H
—Cl


F105 (a and b)
S
—CHF2
—H
—Br


F106 (a and b)
S
—CHF2
—H
—F


F107 (a and b)
S
—CHF2
—H
—CH3


F108 (a and b)
S
—CHF2
—H
—CF3


F109 (a and b)
S
—CHF2
—H
—OCH3


F110 (a and b)
S
—CHF2
—H
—OCH2CH3


F111 (a and b)
S
—CHF2
—H
—OCF3


F112 (a and b)
S
—CHF2
—H
-tert-butyl


F113 (a and b)
S
—CHF2
—H
-iso-propyl


F114 (a and b)
S
—OH
—Cl
—H


F115 (a and b)
S
—OH
—Br
—H


F116 (a and b)
S
—OH
—F
—H


F117 (a and b)
S
—OH
—CH3
—H


F118 (a and b)
S
—OH
—CF3
—H


F119 (a and b)
S
—OH
—OCH3
—H


F120 (a and b)
S
—OH
—OCH2CH3
—H


F121 (a and b)
S
—OH
—OCF3
—H


F122 (a and b)
S
—OH
-tert-butyl
—H


F123 (a and b)
S
—OH
-iso-propyl
—H


F124 (a and b)
S
—OH
—CH3
—CH3


F125 (a and b)
S
—OH
—H
—H


F126 (a and b)
S
—OH
—H
—Cl


F127 (a and b)
S
—OH
—H
—Br


F128 (a and b)
S
—OH
—H
—F


F129 (a and b)
S
—OH
—H
—CH3


F130 (a and b)
S
—OH
—H
—CF3


F131 (a and b)
S
—OH
—H
—OCH3


F132 (a and b)
S
—OH
—H
—OCH2CH3


F133 (a and b)
S
—OH
—H
—OCF3


F134 (a and b)
S
—OH
—H
-tert-butyl


F135 (a and b)
S
—OH
—H
-iso-propyl


F136 (a and b)
S
—NO2
—Cl
—H


F137 (a and b)
S
—NO2
—Br
—H


F138 (a and b)
S
—NO2
—F
—H


F139 (a and b)
S
—NO2
—CH3
—H


F140 (a and b)
S
—NO2
—CF3
—H


F141 (a and b)
S
—NO2
—OCH3
—H


F142 (a and b)
S
—NO2
—OCH2CH3
—H


F143 (a and b)
S
—NO2
—OCF3
—H


F144 (a and b)
S
—NO2
-tert-butyl
—H


F145 (a and b)
S
—NO2
-iso-propyl
—H


F146 (a and b)
S
—NO2
—CH3
—CH3


F147 (a and b)
S
—NO2
—H
—H


F148 (a and b)
S
—NO2
—H
—Cl


F149 (a and b)
S
—NO2
—H
—Br


F150 (a and b)
S
—NO2
—H
—F


F151 (a and b)
S
—NO2
—H
—CH3


F152 (a and b)
S
—NO2
—H
—CF3


F153 (a and b)
S
—NO2
—H
—OCH3


F154 (a and b)
S
—NO2
—H
—OCH2CH3


F155 (a and b)
S
—NO2
—H
-OCF3


F156 (a and b)
S
—NO2
—H
-tert-butyl


F157 (a and b)
S
—NO2
—H
-iso-propyl


F158 (a and b)
S
—CN
—Br
—H


F159 (a and b)
S
—CN
—Cl
—H


F160 (a and b)
S
—CN
—F
—H


F161 (a and b)
S
—CN
—CH3
—H


F162 (a and b)
S
—CN
—CF3
—H


F163 (a and b)
S
—CN
—OCH3
—H


F164 (a and b)
S
—CN
—OCH2CH3
—H


F165 (a and b)
S
—CN
—OCF3
—H


F166 (a and b)
S
—CN
-tert-butyl
—H


F167 (a and b)
S
—CN
-iso-propyl
—H


F168 (a and b)
S
—CN
—CH3
—CH3


F169 (a and b)
S
—CN
—H
—H


F170 (a and b)
S
—CN
—H
—Cl


F171 (a and b)
S
—CN
—H
—Br


F172 (a and b)
S
—CN
—H
—F


F173 (a and b)
S
—CN
—H
—CH3


F174 (a and b)
S
—CN
—H
—CF3


F175 (a and b)
S
—CN
—H
—OCH3


F176 (a and b)
S
—CN
—H
—OCH2CH3


F177 (a and b)
S
—CN
—H
—OCF3


F178 (a and b)
S
—CN
—H
-tert-butyl


F179 (a and b)
S
—CN
—H
-iso-propyl


F180 (a and b)
S
—Br
—Br
—H


F181 (a and b)
S
—Br
—Cl
—H


F182 (a and b)
S
—Br
—F
—H


F183 (a and b)
S
—Br
—CH3
—H


F184 (a and b)
S
—Br
—CF3
—H


F185 (a and b)
S
—Br
—OCH3
—H


F186 (a and b)
S
—Br
—OCH2CH3
—H


F187 (a and b)
S
—Br
—OCF3
—H


F188 (a and b)
S
—Br
-tert-butyl
—H


F189 (a and b)
S
—Br
-iso-propyl
—H


F190 (a and b)
S
—Br
—CH3
—CH3


F191 (a and b)
S
—Br
—H
—H


F192 (a and b)
S
—Br
—H
—Cl


F193 (a and b)
S
—Br
—H
—Br


F194 (a and b)
S
—Br
—H
—F


F195 (a and b)
S
—Br
—H
—CH3


F196 (a and b)
S
—Br
—H
—CF3


F197 (a and b)
S
—Br
—H
—OCH3


F198 (a and b)
S
—Br
—H
—OCH2CH3


F199 (a and b)
S
—Br
—H
—OCF3


F200 (a and b)
S
—Br
—H
-tert-butyl


F201 (a and b)
S
—Br
—H
-iso-propyl


F202 (a and b)
S
—I
—Cl
—H


F203 (a and b)
S
—I
—Br
—H


F204 (a and b)
S
—I
—F
—H


F205 (a and b)
S
—I
—CH3
—H


F206 (a and b)
S
—I
—CF3
—H


F207 (a and b)
S
—I
—OCH3
—H


F208 (a and b)
S
—I
—OCH2CH3
—H


F209 (a and b)
S
—I
—OCF3
—H


F210 (a and b)
S
—I
-tert-butyl
—H


F211 (a and b)
S
—I
-iso-propyl
—H


F212 (a and b)
S
—I
—CH3
—CH3


F213 (a and b)
S
—I
—H
—H


F214 (a and b)
S
—I
—H
—Cl


F215 (a and b)
S
—I
—H
—Br


F216 (a and b)
S
—I
—H
—F


F217 (a and b)
S
—I
—H
—CH3


F218 (a and b)
S
—I
—H
—CF3


F219 (a and b)
S
—I
—H
—OCH3


F220 (a and b)
S
—I
—H
—OCH2CH3


F221 (a and b)
S
—I
—H
—OCF3


F222 (a and b)
S
—I
—H
-tert-butyl


F223 (a and b)
S
—I
—H
-iso-propyl


F224 (a and b)
O
—H
—Cl
—H


F225 (a and b)
O
—H
—Br
—H


F226 (a and b)
O
—H
—F
—H


F227 (a and b)
O
—H
—CH3
—H


F228 (a and b)
O
—H
—CF3
—H


F229 (a and b)
O
—H
—OCH3
—H


F230 (a and b)
O
—H
—OCH2CH3
—H


F231 (a and b)
O
—H
—OCF3
—H


F232 (a and b)
O
—H
-tert-butyl
—H


F233 (a and b)
O
—H
-iso-propyl
—H


F234 (a and b)
O
—H
—CH3
—CH3


F235 (a and b)
O
—H
—H
—H


F236 (a and b)
O
—H
—H
—Cl


F237 (a and b)
O
—H
—H
—Br


F238 (a and b)
O
—H
—H
—F


F239 (a and b)
O
—H
—H
—CH3


F240 (a and b)
O
—H
—H
—CF3


F241 (a and b)
O
—H
—H
—OCH3


F242 (a and b)
O
—H
—H
—OCH2CH3


F243 (a and b)
O
—H
—H
—OCF3


F244 (a and b)
O
—H
—H
-tert-butyl


F245 (a and b)
O
—H
—H
-iso-propyl


F246 (a and b)
O
—Cl
—Cl
—H


F247 (a and b)
O
—Cl
—Br
—H


F248 (a and b)
O
—Cl
—F
—H


F249 (a and b)
O
—Cl
—CH3
—H


F250 (a and b)
O
—Cl
—CF3
—H


F251 (a and b)
O
—Cl
—OCH3
—H


F252 (a and b)
O
—Cl
—OCH2CH3
—H


F253 (a and b)
O
—Cl
—OCF3
—H


F254 (a and b)
O
—Cl
-tert-butyl
—H


F255 (a and b)
O
—Cl
-iso-propyl
—H


F256 (a and b)
O
—Cl
—CH3
—CH3


F257 (a and b)
O
—Cl
—H
—H


F258 (a and b)
O
—Cl
—H
—Cl


F259 (a and b)
O
—Cl
—H
—Br


F260 (a and b)
O
—Cl
—H
—F


F261 (a and b)
O
—Cl
—H
—CH3


F262 (a and b)
O
—Cl
—H
—CF3


F263 (a and b)
O
—Cl
—H
—OCH3


F264 (a and b)
O
—Cl
—H
—OCH2CH3


F265 (a and b)
O
—Cl
—H
—OCF3


F266 (a and b)
O
—Cl
—H
-tert-butyl


F267 (a and b)
O
—Cl
—H
-iso-propyl


F268 (a and b)
O
—Cl
—H
—OCF3


F269 (a and b)
O
—Cl
—H
-tert-butyl


F270 (a and b)
O
—Cl
—H
-iso-propyl


F271 (a and b)
O
—CH3
—Cl
—H


F272 (a and b)
O
—CH3
—Br
—H


F273 (a and b)
O
—CH3
—F
—H


F274 (a and b)
O
—CH3
—CH3
—H


F275 (a and b)
O
—CH3
—CF3
—H


F276 (a and b)
O
—CH3
—OCH3
—H


F277 (a and b)
O
—CH3
—OCH2CH3
—H


F278 (a and b)
O
—CH3
—OCF3
—H


F279 (a and b)
O
—CH3
-tert-butyl
—H


F280 (a and b)
O
—CH3
-iso-propyl
—H


F281 (a and b)
O
—CH3
—CH3
—CH3


F282 (a and b)
O
—CH3
—H
—H


F283 (a and b)
O
—CH3
—H
—Cl


F284 (a and b)
O
—CH3
—H
—Br


F285 (a and b)
O
—CH3
—H
—F


F286 (a and b)
O
—CH3
—H
—CH3


F287 (a and b)
O
—CH3
—H
—CF3


F288 (a and b)
O
—CH3
—H
—OCH3


F289 (a and b)
O
—CH3
—H
—OCH2CH3


F290 (a and b)
O
—CH3
—H
—OCF3


F291 (a and b)
O
—CH3
—H
-tert-butyl


F292 (a and b)
O
—CH3
—H
-iso-propyl


F293 (a and b)
O
—CF3
—Cl
—H


F294 (a and b)
O
—CF3
—Br
—H


F295 (a and b)
O
—CF3
—F
—H


F296 (a and b)
O
—CF3
—CH3
—H


F297 (a and b)
O
—CF3
—CF3
—H


F298 (a and b)
O
—CF3
—OCH3
—H


F299 (a and b)
O
—CF3
—OCH2CH3
—H


F300 (a and b)
O
—CF3
—OCF3
—H


F301 (a and b)
O
—CF3
-tert-butyl
—H


F302 (a and b)
O
—CF3
-iso-propyl
—H


F303 (a and b)
O
—CF3
—CH3
—CH3


F304 (a and b)
O
—CF3
—H
—H


F305 (a and b)
O
—CF3
—H
—Cl


F306 (a and b)
O
—CF3
—H
—Br


F307 (a and b)
O
—CF3
—H
—F


F308 (a and b)
O
—CF3
—H
—CH3


F309 (a and b)
O
—CF3
—H
—CF3


F310 (a and b)
O
—CF3
—H
—OCH3


F311 (a and b)
O
—CF3
—H
—OCH2CH3


F312 (a and b)
O
—CF3
—H
—OCF3


F313 (a and b)
O
—CF3
—H
-tert-butyl


F314 (a and b)
O
—CF3
—H
-iso-propyl


F315 (a and b)
O
—CHF2
—Cl
—H


F316 (a and b)
O
—CHF2
—Br
—H


F317 (a and b)
O
—CHF2
—F
—H


F318 (a and b)
O
—CHF2
—CH3
—H


F319 (a and b)
O
—CHF2
—CF3
—H


F320 (a and b)
O
—CHF2
—OCH3
—H


F321 (a and b)
O
—CHF2
—OCH2CH3
—H


F322 (a and b)
O
—CHF2
—OCF3
—H


F323 (a and b)
O
—CHF2
-tert-butyl
—H


F324 (a and b)
O
—CHF2
-iso-propyl
—H


F325 (a and b)
O
—CHF2
—CH3
—CH3


F326 (a and b)
O
—CHF2
—H
—H


F327 (a and b)
O
—CHF2
—H
—Cl


F328 (a and b)
O
—CHF2
—H
—Br


F329 (a and b)
O
—CHF2
—H
—F


F330 (a and b)
O
—CHF2
—H
—CH3


F331 (a and b)
O
—CHF2
—H
—CF3


F332 (a and b)
O
—CHF2
—H
—OCH3


F333 (a and b)
O
—CHF2
—H
—OCH2CH3


F334 (a and b)
O
—CHF2
—H
—OCF3


F335 (a and b)
O
—CHF2
—H
-tert-butyl


F336 (a and b)
O
—CHF2
—H
-iso-propyl


F337 (a and b)
O
—OH
—Cl
—H


F338 (a and b)
O
—OH
—Br
—H


F339 (a and b)
O
—OH
—F
—H


F340 (a and b)
O
—OH
—CH3
—H


F341 (a and b)
O
—OH
—CF3
—H


F342 (a and b)
O
—OH
—OCH3
—H


F343 (a and b)
O
—OH
—OCH2CH3
—H


F344 (a and b)
O
—OH
—OCF3
—H


F345 (a and b)
O
—OH
-tert-butyl
—H


F346 (a and b)
O
—OH
-iso-propyl
—H


F347 (a and b)
O
—OH
—CH3
—CH3


F348 (a and b)
O
—OH
—H
—H


F349 (a and b)
O
—OH
—H
—Cl


F350 (a and b)
O
—OH
—H
—Br


F351 (a and b)
O
—OH
—H
—F


F352 (a and b)
O
—OH
—H
—CH3


F353 (a and b)
O
—OH
—H
—CF3


F354 (a and b)
O
—OH
—H
—OCH3


F355 (a and b)
O
—OH
—H
—OCH2CH3


F356 (a and b)
O
—OH
—H
—OCF3


F357 (a and b)
O
—OH
—H
-tert-butyl


F358 (a and b)
O
—OH
—H
-iso-propyl


F359 (a and b)
O
—NO2
—Cl
—H


F360 (a and b)
O
—NO2
—Br
—H


F361 (a and b)
O
—NO2
—F
—H


F362 (a and b)
O
—NO2
—CH3
—H


F363 (a and b)
O
—NO2
—CF3
—H


F364 (a and b)
O
—NO2
—OCH3
—H


F365 (a and b)
O
—NO2
—OCH2CH3
—H


F366 (a and b)
O
—NO2
—OCF3
—H


F367 (a and b)
O
—NO2
-tert-butyl
—H


F368 (a and b)
O
—NO2
-iso-propyl
—H


F369 (a and b)
O
—NO2
—CH3
—CH3


F370 (a and b)
O
—NO2
—H
—H


F371 (a and b)
O
—NO2
—H
—Cl


F372 (a and b)
O
—NO2
—H
—Br


F373 (a and b)
O
—NO2
—H
—F


F374 (a and b)
O
—NO2
—H
—CH3


F375 (a and b)
O
—NO2
—H
—CF3


F376 (a and b)
O
—NO2
—H
—OCH3


F377 (a and b)
O
—NO2
—H
—OCH2CH3


F378 (a and b)
O
—NO2
—H
—OCF3


F379 (a and b)
O
—NO2
—H
-tert-butyl


F380 (a and b)
O
—NO2
—H
-iso-propyl


F381 (a and b)
O
—CN
—Br
—H


F382 (a and b)
O
—CN
—Cl
—H


F383 (a and b)
O
—CN
—F
—H


F384 (a and b)
O
—CN
—CH3
—H


F385 (a and b)
O
—CN
—CF3
—H


F386 (a and b)
O
—CN
—OCH3
—H


F387 (a and b)
O
—CN
—OCH2CH3
—H


F388 (a and b)
O
—CN
—OCF3
—H


F389 (a and b)
O
—CN
-tert-butyl
—H


F390 (a and b)
O
—CN
-iso-propyl
—H


F391 (a and b)
O
—CN
—CH3
—CH3


F392 (a and b)
O
—CN
—H
—H


F393 (a and b)
O
—CN
—H
—Cl


F394 (a and b)
O
—CN
—H
—Br


F395 (a and b)
O
—CN
—H
—F


F396 (a and b)
O
—CN
—H
—CH3


F397 (a and b)
O
—CN
—H
—CF3


F398 (a and b)
O
—CN
—H
—OCH3


F399 (a and b)
O
—CN
—H
—OCH2CH3


F400 (a and b)
O
—CN
—H
—OCF3


F401 (a and b)
O
—CN
—H
-tert-butyl


F402 (a and b)
O
—CN
—H
-iso-propyl


F403 (a and b)
O
—Br
—Br
—H


F404 (a and b)
O
—Br
—Cl
—H


F405 (a and b)
O
—Br
—F
—H


F406 (a and b)
O
—Br
—CH3
—H


F407 (a and b)
O
—Br
—CF3
—H


F408 (a and b)
O
—Br
—OCH3
—H


F409 (a and b)
O
—Br
—OCH2CH3
—H


F410 (a and b)
O
—Br
—OCF3
—H


F411 (a and b)
O
—Br
-tert-butyl
—H


F412 (a and b)
O
—Br
-iso-propyl
—H


F413 (a and b)
O
—Br
—CH3
—CH3


F414 (a and b)
O
—Br
—H
—H


F415 (a and b)
O
—Br
—H
—Cl


F416 (a and b)
O
—Br
—H
—Br


F417 (a and b)
O
—Br
—H
—F


F418 (a and b)
O
—Br
—H
—CH3


F419 (a and b)
O
—Br
—H
—CF3


F420 (a and b)
O
—Br
—H
—OCH3


F421 (a and b)
O
—Br
—H
—OCH2CH3


F422 (a and b)
O
—Br
—H
—OCF3


F423 (a and b)
O
—Br
—H
-tert-butyl


F424 (a and b)
O
—Br
—H
-iso-propyl


F425 (a and b)
O
—I
—Cl
—H


F426 (a and b)
O
—I
—Br
—H


F427 (a and b)
O
—I
—F
—H


F428 (a and b)
O
—I
—CH3
—H


F429 (a and b)
O
—I
—CF3
—H


F430 (a and b)
O
—I
—OCH3
—H


F431 (a and b)
O
—I
—OCH2CH3
—H


F432 (a and b)
O
—I
—OCF3
—H


F433 (a and b)
O
—I
-tert-butyl
—H


F434 (a and b)
O
—I
-iso-propyl
—H


F435 (a and b)
O
—I
—CH3
—CH3


F436 (a and b)
O
—I
—H
—H


F437 (a and b)
O
—I
—H
—Cl


F438 (a and b)
O
—I
—H
—Br


F439 (a and b)
O
—I
—H
—F


F440 (a and b)
O
—I
—H
—CH3


F441 (a and b)
O
—I
—H
—CF3


F442 (a and b)
O
—I
—H
—OCH3


F443 (a and b)
O
—I
—H
—OCH2CH3


F444 (a and b)
O
—I
—H
—OCF3


F445 (a and b)
O
—I
—H
-tert-butyl


F446 (a and b)
O
—I
—H
-iso-propyl


F447 (a and b)
NH
—H
—Cl
—H


F448 (a and b)
NH
—H
—Br
—H


F449 (a and b)
NH
—H
—F
—H


F450 (a and b)
NH
—H
—CH3
—H


F451 (a and b)
NH
—H
—CF3
—H


F452 (a and b)
NH
—H
—OCH3
—H


F453 (a and b)
NH
—H
—OCH2CH3
—H


F454 (a and b)
NH
—H
—OCF3
—H


F455 (a and b)
NH
—H
-tert-butyl
—H


F456 (a and b)
NH
—H
-iso-propyl
—H


F457 (a and b)
NH
—H
—CH3
—CH3


F458 (a and b)
NH
—H
—H
—H


F459 (a and b)
NH
—H
—H
—Cl


F460 (a and b)
NH
—H
—H
—Br


F461 (a and b)
NH
—H
—H
—F


F462 (a and b)
NH
—H
—H
—CH3


F463 (a and b)
NH
—H
—H
—CF3


F464 (a and b)
NH
—H
—H
—OCH3


F465 (a and b)
NH
—H
—H
—OCH2CH3


F466 (a and b)
NH
—H
—H
—OCF3


F467 (a and b)
NH
—H
—H
-tert-butyl


F468 (a and b)
NH
—H
—H
-iso-propyl


F469 (a and b)
NH
—Cl
—Cl
—H


F470 (a and b)
NH
—Cl
—Br
—H


F471 (a and b)
NH
—Cl
—F
—H


F472 (a and b)
NH
—Cl
—CH3
—H


F473 (a and b)
NH
—Cl
—CF3
—H


F474 (a and b)
NH
—Cl
—OCH3
—H


F475 (a and b)
NH
—Cl
—OCH2CH3
—H


F476 (a and b)
NH
—Cl
—OCF3
—H


F477 (a and b)
NH
—Cl
-tert-butyl
—H


F478 (a and b)
NH
—Cl
-iso-propyl
—H


F479 (a and b)
NH
—Cl
—CH3
—CH3


F480 (a and b)
NH
—Cl
—H
—H


F481 (a and b)
NH
—Cl
—H
—Cl


F482 (a and b)
NH
—Cl
—H
—Br


F483 (a and b)
NH
—Cl
—H
—F


F484 (a and b)
NH
—Cl
—H
—CH3


F485 (a and b)
NH
—Cl
—H
—CF3


F486 (a and b)
NH
—Cl
—H
—OCH3


F487 (a and b)
NH
—Cl
—H
—OCH2CH3


F488 (a and b)
NH
—Cl
—H
—OCF3


F489 (a and b)
NH
—Cl
—H
-tert-butyl


F490 (a and b)
NH
—Cl
—H
-iso-propyl


F491 (a and b)
NH
—Cl
—H
—OCF3


F492 (a and b)
NH
—Cl
—H
-tert-butyl


F493 (a and b)
NH
—Cl
—H
-iso-propyl


F494 (a and b)
NH
—CH3
—Cl
—H


F495 (a and b)
NH
—CH3
—Br
—H


F496 (a and b)
NH
—CH3
—F
—H


F497 (a and b)
NH
—CH3
—CH3
—H


F498 (a and b)
NH
—CH3
—CF3
—H


F499 (a and b)
NH
—CH3
—OCH3
—H


F500 (a and b)
NH
—CH3
—OCH2CH3
—H


F501 (a and b)
NH
—CH3
—OCF3
—H


F502 (a and b)
NH
—CH3
-tert-butyl
—H


F503 (a and b)
NH
—CH3
-iso-propyl
—H


F504 (a and b)
NH
—CH3
—CH3
—CH3


F505 (a and b)
NH
—CH3
—H
—H


F506 (a and b)
NH
—CH3
—H
—Cl


F507 (a and b)
NH
—CH3
—H
—Br


F508 (a and b)
NH
—CH3
—H
—F


F509 (a and b)
NH
—CH3
—H
—CH3


F510 (a and b)
NH
—CH3
—H
—CF3


F511 (a and b)
NH
—CH3
—H
—OCH3


F512 (a and b)
NH
—CH3
—H
—OCH2CH3


F513 (a and b)
NH
—CH3
—H
—OCF3


F514 (a and b)
NH
—CH3
—H
-tert-butyl


F515 (a and b)
NH
—CH3
—H
-iso-propyl


F516 (a and b)
NH
—CF3
—Cl
—H


F517 (a and b)
NH
—CF3
—Br
—H


F518 (a and b)
NH
—CF3
—F
—H


F519 (a and b)
NH
—CF3
—CH3
—H


F520 (a and b)
NH
—CF3
—CF3
—H


F521 (a and b)
NH
—CF3
—OCH3
—H


F522 (a and b)
NH
—CF3
—OCH2CH3
—H


F523 (a and b)
NH
—CF3
—OCF3
—H


F524 (a and b)
NH
—CF3
-tert-butyl
—H


F525 (a and b)
NH
—CF3
-iso-propyl
—H


F526 (a and b)
NH
—CF3
—CH3
—CH3


F527 (a and b)
NH
—CF3
—H
—H


F528 (a and b)
NH
—CF3
—H
—Cl


F529 (a and b)
NH
—CF3
—H
—Br


F530 (a and b)
NH
—CF3
—H
—F


F531 (a and b)
NH
—CF3
—H
—CH3


F532 (a and b)
NH
—CF3
—H
—CF3


F533 (a and b)
NH
—CF3
—H
—OCH3


F534 (a and b)
NH
—CF3
—H
—OCH2CH3


F535 (a and b)
NH
—CF3
—H
—OCF3


F536 (a and b)
NH
—CF3
—H
-tert-butyl


F537 (a and b)
NH
—CF3
—H
-iso-propyl


F538 (a and b)
NH
—CHF2
—Cl
—H


F539 (a and b)
NH
—CHF2
—Br
—H


F540 (a and b)
NH
—CHF2
—F
—H


F541 (a and b)
NH
—CHF2
—CH3
—H


F542 (a and b)
NH
—CHF2
—CF3
—H


F543 (a and b)
NH
—CHF2
—OCH3
—H


F544 (a and b)
NH
—CHF2
—OCH2CH3
—H


F545 (a and b)
NH
—CHF2
—OCF3
—H


F546 (a and b)
NH
—CHF2
-tert-butyl
—H


F547 (a and b)
NH
—CHF2
-iso-propyl
—H


F548 (a and b)
NH
—CHF2
—CH3
—CH3


F549 (a and b)
NH
—CHF2
—H
—H


F550 (a and b)
NH
—CHF2
—H
—Cl


F551 (a and b)
NH
—CHF2
—H
—Br


F552 (a and b)
NH
—CHF2
—H
—F


F553 (a and b)
NH
—CHF2
—H
—CH3


F554 (a and b)
NH
—CHF2
—H
—CF3


F555 (a and b)
NH
—CHF2
—H
—OCH3


F556 (a and b)
NH
—CHF2
—H
—OCH2CH3


F557 (a and b)
NH
—CHF2
—H
—OCF3


F558 (a and b)
NH
—CHF2
—H
-tert-butyl


F559 (a and b)
NH
—CHF2
—H
-iso-propyl


F560 (a and b)
NH
—OH
—Cl
—H


F561 (a and b)
NH
—OH
—Br
—H


F562 (a and b)
NH
—OH
—F
—H


F563 (a and b)
NH
—OH
—CH3
—H


F564 (a and b)
NH
—OH
—CF3
—H


F565 (a and b)
NH
—OH
—OCH3
—H


F566 (a and b)
NH
—OH
—OCH2CH3
—H


F567 (a and b)
NH
—OH
—OCF3
—H


F568 (a and b)
NH
—OH
-tert-butyl
—H


F569 (a and b)
NH
—OH
-iso-propyl
—H


F570 (a and b)
NH
—OH
—CH3
—CH3


F571 (a and b)
NH
—OH
—H
—H


F572 (a and b)
NH
—OH
—H
—Cl


F573 (a and b)
NH
—OH
—H
—Br


F574 (a and b)
NH
—OH
—H
—F


F575 (a and b)
NH
—OH
—H
—CH3


F576 (a and b)
NH
—OH
—H
—CF3


F577 (a and b)
NH
—OH
—H
—OCH3


F578 (a and b)
NH
—OH
—H
—OCH2CH3


F579 (a and b)
NH
—OH
—H
—OCF3


F580 (a and b)
NH
—OH
—H
-tert-butyl


F581 (a and b)
NH
—OH
—H
-iso-propyl


F582 (a and b)
NH
—NO2
—Cl
—H


F583 (a and b)
NH
—NO2
—Br
—H


F584 (a and b)
NH
—NO2
—F
—H


F585 (a and b)
NH
—NO2
—CH3
—H


F586 (a and b)
NH
—NO2
—CF3
—H


F587 (a and b)
NH
—NO2
—OCH3
—H


F588 (a and b)
NH
—NO2
—OCH2CH3
—H


F589 (a and b)
NH
—NO2
—OCF3
—H


F590 (a and b)
NH
—NO2
-tert-butyl
—H


F591 (a and b)
NH
—NO2
-iso-propyl
—H


F592 (a and b)
NH
—NO2
—CH3
—CH3


F593 (a and b)
NH
—NO2
—H
—H


F594 (a and b)
NH
—NO2
—H
—Cl


F595 (a and b)
NH
—NO2
—H
—Br


F596 (a and b)
NH
—NO2
—H
—F


F597 (a and b)
NH
—NO2
—H
—CH3


F598 (a and b)
NH
—NO2
—H
—CF3


F599 (a and b)
NH
—NO2
—H
—OCH3


F600 (a and b)
NH
—NO2
—H
—OCH2CH3


F601 (a and b)
NH
—NO2
—H
—OCF3


F602 (a and b)
NH
—NO2
—H
-tert-butyl


F603 (a and b)
NH
—NO2
—H
-iso-propyl


F604 (a and b)
NH
—CN
—Br
—H


F605 (a and b)
NH
—CN
—Cl
—H


F606 (a and b)
NH
—CN
—F
—H


F607 (a and b)
NH
—CN
—CH3
—H


F608 (a and b)
NH
—CN
—CF3
—H


F609 (a and b)
NH
—CN
—OCH3
—H


F610 (a and b)
NH
—CN
—OCH2CH3
—H


F611 (a and b)
NH
—CN
—OCF3
—H


F612 (a and b)
NH
—CN
-tert-butyl
—H


F613 (a and b)
NH
—CN
-iso-propyl
—H


F614 (a and b)
NH
—CN
—CH3
—CH3


F615 (a and b)
NH
—CN
—H
—H


F616 (a and b)
NH
—CN
—H
—Cl


F617 (a and b)
NH
—CN
—H
—Br


F618 (a and b)
NH
—CN
—H
—F


F619 (a and b)
NH
—CN
—H
—CH3


F620 (a and b)
NH
—CN
—H
—CF3


F621 (a and b)
NH
—CN
—H
—OCH3


F622 (a and b)
NH
—CN
—H
—OCH2CH3


F623 (a and b)
NH
—CN
—H
—OCF3


F624 (a and b)
NH
—CN
—H
-tert-butyl


F625 (a and b)
NH
—CN
—H
-iso-propyl


F626 (a and b)
NH
—Br
—Br
—H


F627 (a and b)
NH
—Br
—Cl
—H


F628 (a and b)
NH
—Br
—F
—H


F629 (a and b)
NH
—Br
—CH3
—H


F630 (a and b)
NH
—Br
—CF3
—H


F631 (a and b)
NH
—Br
—OCH3
—H


F632 (a and b)
NH
—Br
—OCH2CH3
—H


F633 (a and b)
NH
—Br
—OCF3
—H


F634 (a and b)
NH
—Br
-tert-butyl
—H


F635 (a and b)
NH
—Br
-iso-propyl
—H


F636 (a and b)
NH
—Br
—CH3
—CH3


F637 (a and b)
NH
—Br
—H
—H


F638 (a and b)
NH
—Br
—H
—Cl


F639 (a and b)
NH
—Br
—H
—Br


F640 (a and b)
NH
—Br
—H
—F


F641 (a and b)
NH
—Br
—H
—CH3


F642 (a and b)
NH
—Br
—H
—CF3


F643 (a and b)
NH
—Br
—H
—OCH3


F644 (a and b)
NH
—Br
—H
—OCH2CH3


F645 (a and b)
NH
—Br
—H
—OCF3


F646 (a and b)
NH
—Br
—H
-tert-butyl


F647 (a and b)
NH
—Br
—H
-iso-propyl


F648 (a and b)
NH
—I
—Cl
—H


F649 (a and b)
NH
—I
—Br
—H


F650 (a and b)
NH
—I
—F
—H


F651 (a and b)
NH
—I
—CH3
—H


F652 (a and b)
NH
—I
—CF3
—H


F653 (a and b)
NH
—I
—OCH3
—H


F654 (a and b)
NH
—I
—OCH2CH3
—H


F655 (a and b)
NH
—I
—OCF3
—H


F656 (a and b)
NH
—I
-tert-butyl
—H


F657 (a and b)
NH
—I
-iso-propyl
—H


F658 (a and b)
NH
—I
—CH3
—CH3


F659 (a and b)
NH
—I
—H
—H


F660 (a and b)
NH
—I
—H
—Cl


F661 (a and b)
NH
—I
—H
—Br


F662 (a and b)
NH
—I
—H
—F


F663 (a and b)
NH
—I
—H
—CH3


F664 (a and b)
NH
—I
—H
—CF3


F665 (a and b)
NH
—I
—H
—OCH3


F666 (a and b)
NH
—I
—H
—OCH2CH3


F667 (a and b)
NH
—I
—H
—OCF3


F668 (a and b)
NH
—I
—H
-tert-butyl


F669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 7








(Ig)




embedded image













and pharmaceutically acceptable salts thereof, wherein:









Compound
R1
R8a





G01 (a and b)
—H
—H


G02 (a and b)
—H
-tert-butyl


G03 (a and b)
—H
-iso-butyl


G04 (a and b)
—H
-sec-butyl


G05 (a and b)
—H
-iso-propyl


G06 (a and b)
—H
-n-propyl


G07 (a and b)
—H
-cyclohexyl


G08 (a and b)
—H
-tert-butoxy


G09 (a and b)
—H
-isopropoxy


G10 (a and b)
—H
—CF3


G11 (a and b)
—H
—CH2CF3


G12 (a and b)
—H
—OCF3


G13 (a and b)
—H
—Cl


G14 (a and b)
—H
—Br


G15 (a and b)
—H
—I


G16 (a and b)
—H
-n-butyl


G17 (a and b)
—H
—CH3


G18 (a and b)
—H
—SCF3


G19 (a and b)
—H
—N(CH2CH3)2


G20 (a and b)
—H
—OCF2CHF2


G21 (a and b)
—H
—C(OH)(CF3)2


G22 (a and b)
—H
-(1,1-dimethyl-pentyl)


G23 (a and b)
—H
-(1,1-dimethyl-acetic acid) ethyl ester


G24 (a and b)
—H
—N-piperidinyl


G25 (a and b)
—Cl
—H


G26 (a and b)
—Cl
-tert-butyl


G27 (a and b)
—Cl
-iso-butyl


G28 (a and b)
—Cl
-sec-butyl


G29 (a and b)
—Cl
-iso-propyl


G30 (a and b)
—Cl
-n-propyl


G31 (a and b)
—Cl
-cyclohexyl


G32 (a and b)
—Cl
-tert-butoxy


G33 (a and b)
—Cl
-isopropoxy


G34 (a and b)
—Cl
—CF3


G35 (a and b)
—Cl
—CH2CF3


G36 (a and b)
—Cl
—OCF3


G37 (a and b)
—Cl
—Cl


G38 (a and b)
—Cl
—Br


G39 (a and b)
—Cl
—I


G40 (a and b)
—Cl
-n-butyl


G41 (a and b)
—Cl
—CH3


G42 (a and b)
—Cl
—SCF3


G43 (a and b)
—Cl
—N(CH2CH3)2


G44 (a and b)
—Cl
—OCF2CHF2


G45 (a and b)
—Cl
—C(OH)(CF3)2


G46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)


G47 (a and b)
—Cl
-(1,1-dimethyl-acetic acid) ethyl ester


G48 (a and b)
—Cl
—N-piperidinyl


G49 (a and b)
—F
—H


G50 (a and b)
—F
-tert-butyl


G51 (a and b)
—F
-iso-butyl


G52 (a and b)
—F
-sec-butyl


G53 (a and b)
—F
-iso-propyl


G54 (a and b)
—F
-n-propyl


G55 (a and b)
—F
-cyclohexyl


G56 (a and b)
—F
-tert-butoxy


G57 (a and b)
—F
-isopropoxy


G58 (a and b)
—F
—CF3


G59 (a and b)
—F
—CH2CF3


G60 (a and b)
—F
—OCF3


G61 (a and b)
—F
—Cl


G62 (a and b)
—F
—Br


G63 (a and b)
—F
—I


G64 (a and b)
—F
-n-butyl


G65 (a and b)
—F
—CH3


G66 (a and b)
—F
—SCF3


G67 (a and b)
—F
—N(CH2CH3)2


G68 (a and b)
—F
—OCF2CHF2


G69 (a and b)
—F
—C(OH)(CF3)2


G70 (a and b)
—F
-(1,1-dimethyl-pentyl)


G71 (a and b)
—F
-(1,1-dimethyl-acetic acid) ethyl ester


G72 (a and b)
—F
—N-piperidinyl


G73 (a and b)
—CH3
—H


G74 (a and b)
—CH3
-iso-butyl


G75 (a and b)
—CH3
-tert-butyl


G76 (a and b)
—CH3
-sec-butyl


G77 (a and b)
—CH3
-iso-propyl


G78 (a and b)
—CH3
-n-propyl


G79 (a and b)
—CH3
-cyclohexyl


G80 (a and b)
—CH3
-tert-butoxy


G81 (a and b)
—CH3
-isopropoxy


G82 (a and b)
—CH3
—CF3


G83 (a and b)
—CH3
—CH2CF3


G84 (a and b)
—CH3
—OCF3


G85 (a and b)
—CH3
—Cl


G86 (a and b)
—CH3
—Br


G87 (a and b)
—CH3
—I


G88 (a and b)
—CH3
-n-butyl


G89 (a and b)
—CH3
—CH3


G90 (a and b)
—CH3
—SCF3


G91 (a and b)
—CH3
—N(CH2CH3)2


G92 (a and b)
—CH3
—OCF2CHF2


G93 (a and b)
—CH3
—C(OH)(CF3)2


G94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)


G95 (a and b)
—CH3
-(1,1-dimethyl-acetic acid) ethyl ester


G96 (a and b)
—CH3
—N-piperidinyl


G97 (a and b)
—CF3
—H


G98 (a and b)
—CF3
-tert-butyl


G99 (a and b)
—CF3
-iso-butyl


G100 (a and b)
—CF3
-sec-butyl


G101 (a and b)
—CF3
-iso-propyl


G102 (a and b)
—CF3
-n-propyl


G103 (a and b)
—CF3
-cyclohexyl


G104 (a and b)
—CF3
-tert-butoxy


G105 (a and b)
—CF3
-isopropoxy


G106 (a and b)
—CF3
—CF3


G107 (a and b)
—CF3
—CH2CF3


G108 (a and b)
—CF3
—OCF3


G109 (a and b)
—CF3
—Cl


G110 (a and b)
—CF3
—Br


G111 (a and b)
—CF3
—I


G112 (a and b)
—CF3
-n-butyl


G113 (a and b)
—CF3
—CH3


G114 (a and b)
—CF3
—SCF3


G115 (a and b)
—CF3
—N(CH2CH3)2


G116 (a and b)
—CF3
—OCF2CHF2


G117 (a and b)
—CF3
—C(OH)(CF3)2


G118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)


G119 (a and b)
—CF3
-(1,1-dimethyl-acetic acid) ethyl ester


G120 (a and b)
—CF3
—N-piperidinyl


G121 (a and b)
—CHF2
-tert-butyl


G122 (a and b)
—CHF2
—H


G123 (a and b)
—CHF2
-iso-butyl


G124 (a and b)
—CHF2
-sec-butyl


G125 (a and b)
—CHF2
-iso-propyl


G126 (a and b)
—CHF2
-n-propyl


G127 (a and b)
—CHF2
-cyclohexyl


G128 (a and b)
—CHF2
-tert-butoxy


G129 (a and b)
—CHF2
-isopropoxy


G130 (a and b)
—CHF2
—CF3


G131 (a and b)
—CHF2
—CH2CF3


G132 (a and b)
—CHF2
—OCF3


G133 (a and b)
—CHF2
—Cl


G134 (a and b)
—CHF2
—Br


G135 (a and b)
—CHF2
—I


G136 (a and b)
—CHF2
-n-butyl


G137 (a and b)
—CHF2
—CH3


G138 (a and b)
—CHF2
—SCF3


G139 (a and b)
—CHF2
—N(CH2CH3)2


G140 (a and b)
—CHF2
—OCF2CHF2


G141 (a and b)
—CHF2
—C(OH)(CF3)2


G142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)


G143 (a and b)
—CHF2
-(1,1-dimethyl-acetic acid) ethyl ester


G144 (a and b)
—CHF2
—N-piperidinyl


G145 (a and b)
—OH
—H


G146 (a and b)
—OH
-tert-butyl


G147 (a and b)
—OH
-iso-butyl


G148 (a and b)
—OH
-sec-butyl


G149 (a and b)
—OH
-iso-propyl


G150 (a and b)
—OH
-n-propyl


G151 (a and b)
—OH
-cyclohexyl


G152 (a and b)
—OH
-tert-butoxy


G153 (a and b)
—OH
-isopropoxy


G154 (a and b)
—OH
—CF3


G155 (a and b)
—OH
—CH2CF3


G156 (a and b)
—OH
—OCF3


G157 (a and b)
—OH
—Cl


G158 (a and b)
—OH
—Br


G159 (a and b)
—OH
—I


G160 (a and b)
—OH
-n-butyl


G161 (a and b)
—OH
—CH3


G162 (a and b)
—OH
—SCF3


G163 (a and b)
—OH
—N(CH2CH3)2


G164 (a and b)
—OH
—OCF2CHF2


G165 (a and b)
—OH
—C(OH)(CF3)2


G166 (a and b)
—OH
-(1,1-dimethyl-pentyl)


G167 (a and b)
—OH
-(1,1-dimethyl-acetic acid) ethyl ester


G168 (a and b)
—OH
—N-piperidinyl


G169 (a and b)
—NO2
—H


G170 (a and b)
—NO2
-tert-butyl


G171 (a and b)
—NO2
-iso-butyl


G172 (a and b)
—NO2
-sec-butyl


G173 (a and b)
—NO2
-iso-propyl


G174 (a and b)
—NO2
-n-propyl


G175 (a and b)
—NO2
-cyclohexyl


G176 (a and b)
—NO2
-tert-butoxy


G177 (a and b)
—NO2
-isopropoxy


G178 (a and b)
—NO2
—CF3


G179 (a and b)
—NO2
—CH2CF3


G180 (a and b)
—NO2
—OCF3


G181 (a and b)
—NO2
—Cl


G182 (a and b)
—NO2
—Br


G183 (a and b)
—NO2
—I


G184 (a and b)
—NO2
-n-butyl


G185 (a and b)
—NO2
—CH3


G186 (a and b)
—NO2
—SCF3


G187 (a and b)
—NO2
—N(CH2CH3)2


G188 (a and b)
—NO2
—OCF2CHF2


G189 (a and b)
—NO2
—C(OH)(CF3)2


G190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)


G191 (a and b)
—NO2
-(1,1-dimethyl-acetic acid) ethyl ester


G192 (a and b)
—NO2
—N-piperidinyl


G193 (a and b)
—CN
—H


G194 (a and b)
—CN
-tert-butyl


G195 (a and b)
—CN
-iso-butyl


G196 (a and b)
—CN
-sec-butyl


G197 (a and b)
—CN
-iso-propyl


G198 (a and b)
—CN
-n-propyl


G199 (a and b)
—CN
-cyclohexyl


G200 (a and b)
—CN
-tert-butoxy


G201 (a and b)
—CN
-isopropoxy


G202 (a and b)
—CN
—CF3


G203 (a and b)
—CN
—CH2CF3


G204 (a and b)
—CN
—OCF3


G205 (a and b)
—CN
—Cl


G206 (a and b)
—CN
—Br


G207 (a and b)
—CN
—I


G208 (a and b)
—CN
-n-butyl


G209 (a and b)
—CN
—CH3


G210 (a and b)
—CN
—SCF3


G211 (a and b)
—CN
—N(CH2CH3)2


G212 (a and b)
—CN
—OCF2CHF2


G213 (a and b)
—CN
—C(OH)(CF3)2


G214 (a and b)
—CN
-(1,1-dimethyl-pentyl)


G215 (a and b)
—CN
-(1,1-dimethyl-acetic acid) ethyl ester


G216 (a and b)
—CN
—N-piperidinyl


G217 (a and b)
—Br
—H


G218 (a and b)
—Br
-tert-butyl


G219 (a and b)
—Br
-iso-butyl


G220 (a and b)
—Br
-sec-butyl


G221 (a and b)
—Br
-iso-propyl


G222 (a and b)
—Br
-n-propyl


G223 (a and b)
—Br
-cyclohexyl


G224 (a and b)
—Br
-tert-butoxy


G225 (a and b)
—Br
-isopropoxy


G226 (a and b)
—Br
—CF3


G227 (a and b)
—Br
—CH2CF3


G228 (a and b)
—Br
—OCF3


G229 (a and b)
—Br
—Cl


G230 (a and b)
—Br
—Br


G231 (a and b)
—Br
—I


G232 (a and b)
—Br
-n-butyl


G233 (a and b)
—Br
—CH3


G234 (a and b)
—Br
—SCF3


G235 (a and b)
—Br
—N(CH2CH3)2


G236 (a and b)
—Br
—OCF2CHF2


G237 (a and b)
—Br
—C(OH)(CF3)2


G238 (a and b)
—Br
-(1,1-dimethyl-pentyl)


G239 (a and b)
—Br
-(1,1-dimethyl-acetic acid) ethyl ester


G240 (a and b)
—Br
—N-piperidinyl


G241 (a and b)
—I
-tert-butyl


G242 (a and b)
—I
—H


G243 (a and b)
—I
-iso-butyl


G244 (a and b)
—I
-sec-butyl


G245 (a and b)
—I
-iso-propyl


G246 (a and b)
—I
-n-propyl


G247 (a and b)
—I
-cyclohexyl


G248 (a and b)
—I
-tert-butoxy


G249 (a and b)
—I
-isopropoxy


G250 (a and b)
—I
—CF3


G251 (a and b)
—I
—CH2CF3


G252 (a and b)
—I
—OCF3


G253 (a and b)
—I
—Cl


G254 (a and b)
—I
—Br


G255 (a and b)
—I
—I


G256 (a and b)
—I
-n-butyl


G257 (a and b)
—I
—CH3


G258 (a and b)
—I
—SCF3


G259 (a and b)
—I
—N(CH2CH3)2


G260 (a and b)
—I
—OCF2CHF2


G261 (a and b)
—I
—C(OH)(CF3)2


G262 (a and b)
—I
-(1,1-dimethyl-pentyl)


G263 (a and b)
—I
-(1,1-dimethyl-acetic acid) ethyl ester


G264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 8








(Ih)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
Y
R1
(R8)a
(R8)b





H01 (a and b)
S
—H
—Cl
—H


H02 (a and b)
S
—H
—Br
—H


H03 (a and b)
S
—H
—F
—H


H04 (a and b)
S
—H
—CH3
—H


H05 (a and b)
S
—H
—CF3
—H


H06 (a and b)
S
—H
—OCH3
—H


H07 (a and b)
S
—H
—OCH2CH3
—H


H08 (a and b)
S
—H
—OCF3
—H


H09 (a and b)
S
—H
-tert-butyl
—H


H10 (a and b)
S
—H
-iso-propyl
—H


H11 (a and b)
S
—H
—CH3
—CH3


H12 (a and b)
S
—H
—H
—H


H13 (a and b)
S
—H
—H
—Cl


H14 (a and b)
S
—H
—H
—Br


H15 (a and b)
S
—H
—H
—F


H16 (a and b)
S
—H
—H
—CH3


H17 (a and b)
S
—H
—H
—CF3


H18 (a and b)
S
—H
—H
—OCH3


H19 (a and b)
S
—H
—H
—OCH2CH3


H20 (a and b)
S
—H
—H
—OCF3


H21 (a and b)
S
—H
—H
-tert-butyl


H22 (a and b)
S
—H
—H
-iso-propyl


H23 (a and b)
S
—Cl
—Cl
—H


H24 (a and b)
S
—Cl
—Br
—H


H25 (a and b)
S
—Cl
—F
—H


H26 (a and b)
S
—Cl
—CH3
—H


H27 (a and b)
S
—Cl
—CF3
—H


H28 (a and b)
S
—Cl
—OCH3
—H


H29 (a and b)
S
—Cl
—OCH2CH3
—H


H30 (a and b)
S
—Cl
—OCF3
—H


H31 (a and b)
S
—Cl
-tert-butyl
—H


H32 (a and b)
S
—Cl
-iso-propyl
—H


H33 (a and b)
S
—Cl
—CH3
—CH3


H34 (a and b)
S
—Cl
—H
—H


H35 (a and b)
S
—Cl
—H
—Cl


H36 (a and b)
S
—Cl
—H
—Br


H37 (a and b)
S
—Cl
—H
—F


H38 (a and b)
S
—Cl
—H
—CH3


H39 (a and b)
S
—Cl
—H
—CF3


H40 (a and b)
S
—Cl
—H
—OCH3


H41 (a and b)
S
—Cl
—H
—OCH2CH3


H42 (a and b)
S
—Cl
—H
—OCF3


H43 (a and b)
S
—Cl
—H
-tert-butyl


H44 (a and b)
S
—Cl
—H
-iso-propyl


H45 (a and b)
S
—Cl
—H
—OCF3


H46 (a and b)
S
—Cl
—H
-tert-butyl


H47 (a and b)
S
—Cl
—H
-iso-propyl


H48 (a and b)
S
—CH3
—Cl
—H


H49 (a and b)
S
—CH3
—Br
—H


H50 (a and b)
S
—CH3
—F
—H


H51 (a and b)
S
—CH3
—CH3
—H


H52 (a and b)
S
—CH3
—CF3
—H


H53 (a and b)
S
—CH3
—OCH3
—H


H54 (a and b)
S
—CH3
—OCH2CH3
—H


H55 (a and b)
S
—CH3
—OCF3
—H


H56 (a and b)
S
—CH3
-tert-butyl
—H


H57 (a and b)
S
—CH3
-iso-propyl
—H


H58 (a and b)
S
—CH3
—CH3
—CH3


H59 (a and b)
S
—CH3
—H
—H


H60 (a and b)
S
—CH3
—H
—Cl


H61 (a and b)
S
—CH3
—H
—Br


H62 (a and b)
S
—CH3
—H
—F


H63 (a and b)
S
—CH3
—H
—CH3


H64 (a and b)
S
—CH3
—H
—CF3


H65 (a and b)
S
—CH3
—H
—OCH3


H66 (a and b)
S
—CH3
—H
—OCH2CH3


H67 (a and b)
S
—CH3
—H
—OCF3


H68 (a and b)
S
—CH3
—H
-tert-butyl


H69 (a and b)
S
—CH3
—H
-iso-propyl


H70 (a and b)
S
—CF3
—Cl
—H


H71 (a and b)
S
—CF3
—Br
—H


H72 (a and b)
S
—CF3
—F
—H


H73 (a and b)
S
—CF3
—CH3
—H


H74 (a and b)
S
—CF3
—CF3
—H


H75 (a and b)
S
—CF3
—OCH3
—H


H76 (a and b)
S
—CF3
—OCH2CH3
—H


H77 (a and b)
S
—CF3
—OCF3
—H


H78 (a and b)
S
—CF3
-tert-butyl
—H


H79 (a and b)
S
—CF3
-iso-propyl
—H


H80 (a and b)
S
—CF3
—CH3
—CH3


H81 (a and b)
S
—CF3
—H
—H


H82 (a and b)
S
—CF3
—H
—Cl


H83 (a and b)
S
—CF3
—H
—Br


H84 (a and b)
S
—CF3
—H
—F


H85 (a and b)
S
—CF3
—H
—CH3


H86 (a and b)
S
—CF3
—H
—CF3


H87 (a and b)
S
—CF3
—H
—OCH3


H88 (a and b)
S
—CF3
—H
—OCH2CH3


H89 (a and b)
S
—CF3
—H
—OCF3


H90 (a and b)
S
—CF3
—H
-tert-butyl


H91 (a and b)
S
—CF3
—H
-iso-propyl


H92 (a and b)
S
—CHF2
—Cl
—H


H93 (a and b)
S
—CHF2
—Br
—H


H94 (a and b)
S
—CHF2
—F
—H


H95 (a and b)
S
—CHF2
—CH3
—H


H96 (a and b)
S
—CHF2
—CF3
—H


H97 (a and b)
S
—CHF2
—OCH3
—H


H98 (a and b)
S
—CHF2
—OCH2CH3
—H


H99 (a and b)
S
—CHF2
—OCF3
—H


H100 (a and b)
S
—CHF2
-tert-butyl
—H


H101 (a and b)
S
—CHF2
-iso-propyl
—H


H102 (a and b)
S
—CHF2
—CH3
—CH3


H103 (a and b)
S
—CHF2
—H
—H


H104 (a and b)
S
—CHF2
—H
—Cl


H105 (a and b)
S
—CHF2
—H
—Br


H106 (a and b)
S
—CHF2
—H
—F


H107 (a and b)
S
—CHF2
—H
—CH3


H108 (a and b)
S
—CHF2
—H
—CF3


H109 (a and b)
S
—CHF2
—H
—OCH3


H110 (a and b)
S
—CHF2
—H
—OCH2CH3


H111 (a and b)
S
—CHF2
—H
—OCF3


H112 (a and b)
S
—CHF2
—H
-tert-butyl


H113 (a and b)
S
—CHF2
—H
-iso-propyl


H114 (a and b)
S
—OH
—Cl
—H


H115 (a and b)
S
—OH
—Br
—H


H116 (a and b)
S
—OH
—F
—H


H117 (a and b)
S
—OH
—CH3
—H


H118 (a and b)
S
—OH
—CF3
—H


H119 (a and b)
S
—OH
—OCH3
—H


H120 (a and b)
S
—OH
—OCH2CH3
—H


H121 (a and b)
S
—OH
—OCF3
—H


H122 (a and b)
S
—OH
-tert-butyl
—H


H123 (a and b)
S
—OH
-iso-propyl
—H


H124 (a and b)
S
—OH
—CH3
—CH3


H125 (a and b)
S
—OH
—H
—H


H126 (a and b)
S
—OH
—H
—Cl


H127 (a and b)
S
—OH
—H
—Br


H128 (a and b)
S
—OH
—H
—F


H129 (a and b)
S
—OH
—H
—CH3


H130 (a and b)
S
—OH
—H
—CF3


H131 (a and b)
S
—OH
—H
—OCH3


H132 (a and b)
S
—OH
—H
—OCH2CH3


H133 (a and b)
S
—OH
—H
—OCF3


H134 (a and b)
S
—OH
—H
-tert-butyl


H135 (a and b)
S
—OH
—H
-iso-propyl


H136 (a and b)
S
—NO2
—Cl
—H


H137 (a and b)
S
—NO2
—Br
—H


H138 (a and b)
S
—NO2
—F
—H


H139 (a and b)
S
—NO2
—CH3
—H


H140 (a and b)
S
—NO2
—CF3
—H


H141 (a and b)
S
—NO2
—OCH3
—H


H142 (a and b)
S
—NO2
—OCH2CH3
—H


H143 (a and b)
S
—NO2
—OCF3
—H


H144 (a and b)
S
—NO2
-tert-butyl
—H


H145 (a and b)
S
—NO2
-iso-propyl
—H


H146 (a and b)
S
—NO2
—CH3
—CH3


H147 (a and b)
S
—NO2
—H
—H


H148 (a and b)
S
—NO2
—H
—C1


H149 (a and b)
S
—NO2
—H
—Br


H150 (a and b)
S
—NO2
—H
—F


H151 (a and b)
S
—NO2
—H
—CH3


H152 (a and b)
S
—NO2
—H
—CF3


H153 (a and b)
S
—NO2
—H
—OCH3


H154 (a and b)
S
—NO2
—H
—OCH2CH3


H155 (a and b)
S
—NO2
—H
—OCF3


H156 (a and b)
S
—NO2
—H
-tert-butyl


H157 (a and b)
S
—NO2
—H
-iso-propyl


H158 (a and b)
S
—CN
—Br
—H


H159 (a and b)
S
—CN
—Cl
—H


H160 (a and b)
S
—CN
—F
—H


H161 (a and b)
S
—CN
—CH3
—H


H162 (a and b)
S
—CN
—CF3
—H


H163 (a and b)
S
—CN
—OCH3
—H


H164 (a and b)
S
—CN
—OCH2CH3
—H


H165 (a and b)
S
—CN
—OCF3
—H


H166 (a and b)
S
—CN
-tert-butyl
—H


H167 (a and b)
S
—CN
-iso-propyl
—H


H168 (a and b)
S
—CN
—CH3
—CH3


H169 (a and b)
S
—CN
—H
—H


H170 (a and b)
S
—CN
—H
—Cl


H171 (a and b)
S
—CN
—H
—Br


H172 (a and b)
S
—CN
—H
—F


H173 (a and b)
S
—CN
—H
—CH3


H174 (a and b)
S
—CN
—H
—CF3


H175 (a and b)
S
—CN
—H
—OCH3


H176 (a and b)
S
—CN
—H
—OCH2CH3


H177 (a and b)
S
—CN
—H
—OCF3


H178 (a and b)
S
—CN
—H
-tert-butyl


H179 (a and b)
S
—CN
—H
-iso-propyl


H180 (a and b)
S
—Br
—Br
—H


H181 (a and b)
S
—Br
—Cl
—H


H182 (a and b)
S
—Br
—F
—H


H183 (a and b)
S
—Br
—CH3
—H


H184 (a and b)
S
—Br
—CF3
—H


H185 (a and b)
S
—Br
—OCH3
—H


H186 (a and b)
S
—Br
—OCH2CH3
—H


H187 (a and b)
S
—Br
—OCF3
—H


H188 (a and b)
S
—Br
-tert-butyl
—H


H189 (a and b)
S
—Br
-iso-propyl
—H


H190 (a and b)
S
—Br
—CH3
—CH3


H191 (a and b)
S
—Br
—H
—H


H192 (a and b)
S
—Br
—H
—Cl


H193 (a and b)
S
—Br
—H
—Br


H194 (a and b)
S
—Br
—H
—F


H195 (a and b)
S
—Br
—H
—CH3


H196 (a and b)
S
—Br
—H
—CF3


H197 (a and b)
S
—Br
—H
—OCH3


H198 (a and b)
S
—Br
—H
—OCH2CH3


H199 (a and b)
S
—Br
—H
—OCF3


H200 (a and b)
S
—Br
—H
-tert-butyl


H201 (a and b)
S
—Br
—H
-iso-propyl


H202 (a and b)
S
—I
—Cl
—H


H203 (a and b)
S
—I
—Br
—H


H204 (a and b)
S
—I
—F
—H


H205 (a and b)
S
—I
—CH3
—H


H206 (a and b)
S
—I
—CF3
—H


H207 (a and b)
S
—I
—OCH3
—H


H208 (a and b)
S
—I
—OCH2CH3
—H


H209 (a and b)
S
—I
—OCF3
—H


H210 (a and b)
S
—I
-tert-butyl
—H


H211 (a and b)
S
—I
-iso-propyl
—H


H212 (a and b)
S
—I
—CH3
—CH3


H213 (a and b)
S
—I
—H
—H


H214 (a and b)
S
—I
—H
—C1


H215 (a and b)
S
—I
—H
—Br


H216 (a and b)
S
—I
—H
—F


H217 (a and b)
S
—I
—H
—CH3


H218 (a and b)
S
—I
—H
—CF3


H219 (a and b)
S
—I
—H
—OCH3


H220 (a and b)
S
—I
—H
—OCH2CH3


H221 (a and b)
S
—I
—H
—OCF3


H222 (a and b)
S
—I
—H
-tert-butyl


H223 (a and b)
S
—I
—H
-iso-propyl


H224 (a and b)
O
—H
—Cl
—H


H225 (a and b)
O
—H
—Br
—H


H226 (a and b)
O
—H
—F
—H


H227 (a and b)
O
—H
—CH3
—H


H228 (a and b)
O
—H
—CF3
—H


H229 (a and b)
O
—H
—OCH3
—H


H230 (a and b)
O
—H
—OCH2CH3
—H


H231 (a and b)
O
—H
—OCF3
—H


H232 (a and b)
O
—H
-tert-butyl
—H


H233 (a and b)
O
—H
-iso-propyl
—H


H234 (a and b)
O
—H
—CH3
—CH3


H235 (a and b)
O
—H
—H
—H


H236 (a and b)
O
—H
—H
—Cl


H237 (a and b)
O
—H
—H
—Br


H238 (a and b)
O
—H
—H
—F


H239 (a and b)
O
—H
—H
—CH3


H240 (a and b)
O
—H
—H
—CF3


H241 (a and b)
O
—H
—H
—OCH3


H242 (a and b)
O
—H
—H
—OCH2CH3


H243 (a and b)
O
—H
—H
—OCF3


H244 (a and b)
O
—H
—H
-tert-butyl


H245 (a and b)
O
—H
—H
-iso-propyl


H246 (a and b)
O
—Cl
—Cl
—H


H247 (a and b)
O
—Cl
—Br
—H


H248 (a and b)
O
—Cl
—F
—H


H249 (a and b)
O
—Cl
—CH3
—H


H250 (a and b)
O
—Cl
—CF3
—H


H251 (a and b)
O
—Cl
—OCH3
—H


H252 (a and b)
O
—Cl
—OCH2CH3
—H


H253 (a and b)
O
—Cl
—OCF3
—H


H254 (a and b)
O
—Cl
-tert-butyl
—H


H255 (a and b)
O
—Cl
-iso-propyl
—H


H256 (a and b)
O
—Cl
—CH3
—CH3


H257 (a and b)
O
—Cl
—H
—H


H258 (a and b)
O
—Cl
—H
—Cl


H259 (a and b)
O
—Cl
—H
—Br


H260 (a and b)
O
—Cl
—H
—F


H261 (a and b)
O
—Cl
—H
—CH3


H262 (a and b)
O
—Cl
—H
—CF3


H263 (a and b)
O
—Cl
—H
—OCH3


H264 (a and b)
O
—Cl
—H
—OCH2CH3


H265 (a and b)
O
—Cl
—H
—OCF3


H266 (a and b)
O
—Cl
—H
-tert-butyl


H267 (a and b)
O
—Cl
—H
-iso-propyl


H268 (a and b)
O
—Cl
—H
—OCF3


H269 (a and b)
O
—Cl
—H
-tert-butyl


H270 (a and b)
O
—Cl
—H
-iso-propyl


H271 (a and b)
O
—CH3
—Cl
—H


H272 (a and b)
O
—CH3
—Br
—H


H273 (a and b)
O
—CH3
—F
—H


H274 (a and b)
O
—CH3
—CH3
—H


H275 (a and b)
O
—CH3
—CF3
—H


H276 (a and b)
O
—CH3
—OCH3
—H


H277 (a and b)
O
—CH3
—OCH2CH3
—H


H278 (a and b)
O
—CH3
—OCF3
—H


H279 (a and b)
O
—CH3
-tert-butyl
—H


H280 (a and b)
O
—CH3
-iso-propyl
—H


H281 (a and b)
O
—CH3
—CH3
—CH3


H282 (a and b)
O
—CH3
—H
—H


H283 (a and b)
O
—CH3
—H
—Cl


H284 (a and b)
O
—CH3
—H
—Br


H285 (a and b)
O
—CH3
—H
—F


H286 (a and b)
O
—CH3
—H
—CH3


H287 (a and b)
O
—CH3
—H
—CF3


H288 (a and b)
O
—CH3
—H
—OCH3


H289 (a and b)
O
—CH3
—H
—OCH2CH3


H290 (a and b)
O
—CH3
—H
—OCF3


H291 (a and b)
O
—CH3
—H
-tert-butyl


H292 (a and b)
O
—CH3
—H
-iso-propyl


H293 (a and b)
O
—CF3
—Cl
—H


H294 (a and b)
O
—CF3
—Br
—H


H295 (a and b)
O
—CF3
—F
—H


H296 (a and b)
O
—CF3
—CH3
—H


H297 (a and b)
O
—CF3
—CF3
—H


H298 (a and b)
O
—CF3
—OCH3
—H


H299 (a and b)
O
—CF3
—OCH2CH3
—H


H300 (a and b)
O
—CF3
—OCF3
—H


H301 (a and b)
O
—CF3
-tert-butyl
—H


H302 (a and b)
O
—CF3
-iso-propyl
—H


H303 (a and b)
O
—CF3
—CH3
—CH3


H304 (a and b)
O
—CF3
—H
—H


H305 (a and b)
O
—CF3
—H
—Cl


H306 (a and b)
O
—CF3
—H
—Br


H307 (a and b)
O
—CF3
—H
—F


H308 (a and b)
O
—CF3
—H
—CH3


H309 (a and b)
O
—CF3
—H
—CF3


H310 (a and b)
O
—CF3
—H
—OCH3


H311 (a and b)
O
—CF3
—H
—OCH2CH3


H312 (a and b)
O
—CF3
—H
—OCF3


H313 (a and b)
O
—CF3
—H
-tert-butyl


H314 (a and b)
O
—CF3
—H
-iso-propyl


H315 (a and b)
O
—CHF2
—Cl
—H


H316 (a and b)
O
—CHF2
—Br
—H


H317 (a and b)
O
—CHF2
—F
—H


H318 (a and b)
O
—CHF2
—CH3
—H


H319 (a and b)
O
—CHF2
—CF3
—H


H320 (a and b)
O
—CHF2
—OCH3
—H


H321 (a and b)
O
—CHF2
—OCH2CH3
—H


H322 (a and b)
O
—CHF2
—OCF3
—H


H323 (a and b)
O
—CHF2
-tert-butyl
—H


H324 (a and b)
O
—CHF2
-iso-propyl
—H


H325 (a and b)
O
—CHF2
—CH3
—CH3


H326 (a and b)
O
—CHF2
—H
—H


H327 (a and b)
O
—CHF2
—H
—Cl


H328 (a and b)
O
—CHF2
—H
—Br


H329 (a and b)
O
—CHF2
—H
—F


H330 (a and b)
O
—CHF2
—H
—CH3


H331 (a and b)
O
—CHF2
—H
—CF3


H332 (a and b)
O
—CHF2
—H
—OCH3


H333 (a and b)
O
—CHF2
—H
—OCH2CH3


H334 (a and b)
O
—CHF2
—H
—OCF3


H335 (a and b)
O
—CHF2
—H
-tert-butyl


H336 (a and b)
O
—CHF2
—H
-iso-propyl


H337 (a and b)
O
—OH
—Cl
—H


H338 (a and b)
O
—OH
—Br
—H


H339 (a and b)
O
—OH
—F
—H


H340 (a and b)
O
—OH
—CH3
—H


H341 (a and b)
O
—OH
—CF3
—H


H342 (a and b)
O
—OH
—OCH3
—H


H343 (a and b)
O
—OH
—OCH2CH3
—H


H344 (a and b)
O
—OH
—OCF3
—H


H345 (a and b)
O
—OH
-tert-butyl
—H


H346 (a and b)
O
—OH
-iso-propyl
—H


H347 (a and b)
O
—OH
—CH3
—CH3


H348 (a and b)
O
—OH
—H
—H


H349 (a and b)
O
—OH
—H
—Cl


H350 (a and b)
O
—OH
—H
—Br


H351 (a and b)
O
—OH
—H
—F


H352 (a and b)
O
—OH
—H
—CH3


H353 (a and b)
O
—OH
—H
—CF3


H354 (a and b)
O
—OH
—H
—OCH3


H355 (a and b)
O
—OH
—H
—OCH2CH3


H356 (a and b)
O
—OH
—H
—OCF3


H357 (a and b)
O
—OH
—H
-tert-butyl


H358 (a and b)
O
—OH
—H
-iso-propyl


H359 (a and b)
O
—NO2
—Cl
—H


H360 (a and b)
O
—NO2
—Br
—H


H361 (a and b)
O
—NO2
—F
—H


H362 (a and b)
O
—NO2
—CH3
—H


H363 (a and b)
O
—NO2
—CF3
—H


H364 (a and b)
O
—NO2
—OCH3
—H


H365 (a and b)
O
—NO2
—OCH2CH3
—H


H366 (a and b)
O
—NO2
—OCF3
—H


H367 (a and b)
O
—NO2
-tert-butyl
—H


H368 (a and b)
O
—NO2
-iso-propyl
—H


H369 (a and b)
O
—NO2
—CH3
—CH3


H370 (a and b)
O
—NO2
—H
—H


H371 (a and b)
O
—NO2
—H
—Cl


H372 (a and b)
O
—NO2
—H
—Br


H373 (a and b)
O
—NO2
—H
—F


H374 (a and b)
O
—NO2
—H
—CH3


H375 (a and b)
O
—NO2
—H
—CF3


H376 (a and b)
O
—NO2
—H
—OCH3


H377 (a and b)
O
—NO2
—H
—OCH2CH3


H378 (a and b)
O
—NO2
—H
—OCF3


H379 (a and b)
O
—NO2
—H
-tert-butyl


H380 (a and b)
O
—NO2
—H
-iso-propyl


H381 (a and b)
O
—CN
—Br
—H


H382 (a and b)
O
—CN
—Cl
—H


H383 (a and b)
O
—CN
—F
—H


H384 (a and b)
O
—CN
—CH3
—H


H385 (a and b)
O
—CN
—CF3
—H


H386 (a and b)
O
—CN
—OCH3
—H


H387 (a and b)
O
—CN
—OCH2CH3
—H


H388 (a and b)
O
—CN
—OCF3
—H


H389 (a and b)
O
—CN
-tert-butyl
—H


H390 (a and b)
O
—CN
-iso-propyl
—H


H391 (a and b)
O
—CN
—CH3
—CH3


H392 (a and b)
O
—CN
—H
—H


H393 (a and b)
O
—CN
—H
—Cl


H394 (a and b)
O
—CN
—H
—Br


H395 (a and b)
O
—CN
—H
—F


H396 (a and b)
O
—CN
—H
—CH3


H397 (a and b)
O
—CN
—H
—CF3


H398 (a and b)
O
—CN
—H
—OCH3


H399 (a and b)
O
—CN
—H
—OCH2CH3


H400 (a and b)
O
—CN
—H
—OCF3


H401 (a and b)
O
—CN
—H
-tert-butyl


H402 (a and b)
O
—CN
—H
-iso-propyl


H403 (a and b)
O
—Br
—Br
—H


H404 (a and b)
O
—Br
—Cl
—H


H405 (a and b)
O
—Br
—F
—H


H406 (a and b)
O
—Br
—CH3
—H


H407 (a and b)
O
—Br
—CF3
—H


H408 (a and b)
O
—Br
—OCH3
—H


H409 (a and b)
O
—Br
—OCH2CH3
—H


H410 (a and b)
O
—Br
—OCF3
—H


H411 (a and b)
O
—Br
-tert-butyl
—H


H412 (a and b)
O
—Br
-iso-propyl
—H


H413 (a and b)
O
—Br
—CH3
—CH3


H414 (a and b)
O
—Br
—H
—H


H415 (a and b)
O
—Br
—H
—Cl


H416 (a and b)
O
—Br
—H
—Br


H417 (a and b)
O
—Br
—H
—F


H418 (a and b)
O
—Br
—H
—CH3


H419 (a and b)
O
—Br
—H
—CF3


H420 (a and b)
O
—Br
—H
—OCH3


H421 (a and b)
O
—Br
—H
—OCH2CH3


H422 (a and b)
O
—Br
—H
—OCF3


H423 (a and b)
O
—Br
—H
-tert-butyl


H424 (a and b)
O
—Br
—H
-iso-propyl


H425 (a and b)
O
—I
—Cl
—H


H426 (a and b)
O
—I
—Br
—H


H427 (a and b)
O
—I
—F
—H


H428 (a and b)
O
—I
—CH3
—H


H429 (a and b)
O
—I
—CF3
—H


H430 (a and b)
O
—I
—OCH3
—H


H431 (a and b)
O
—I
—OCH2CH3
—H


H432 (a and b)
O
—I
—OCF3
—H


H433 (a and b)
O
—I
-tert-butyl
—H


H434 (a and b)
O
—I
-iso-propyl
—H


H435 (a and b)
O
—I
—CH3
—CH3


H436 (a and b)
O
—I
—H
—H


H437 (a and b)
O
—I
—H
—Cl


H438 (a and b)
O
—I
—H
—Br


H439 (a and b)
O
—I
—H
—F


H440 (a and b)
O
—I
—H
—CH3


H441 (a and b)
O
—I
—H
—CF3


H442 (a and b)
O
—I
—H
—OCH3


H443 (a and b)
O
—I
—H
—OCH2CH3


H444 (a and b)
O
—I
—H
—OCF3


H445 (a and b)
O
—I
—H
-tert-butyl


H446 (a and b)
O
—I
—H
-iso-propyl


H447 (a and b)
NH
—H
—Cl
—H


H448 (a and b)
NH
—H
—Br
—H


H449 (a and b)
NH
—H
—F
—H


H450 (a and b)
NH
—H
—CH3
—H


H451 (a and b)
NH
—H
—CF3
—H


H452 (a and b)
NH
—H
—OCH3
—H


H453 (a and b)
NH
—H
—OCH2CH3
—H


H454 (a and b)
NH
—H
—OCF3
—H


H455 (a and b)
NH
—H
-tert-butyl
—H


H456 (a and b)
NH
—H
-iso-propyl
—H


H457 (a and b)
NH
—H
—CH3
—CH3


H458 (a and b)
NH
—H
—H
—H


H459 (a and b)
NH
—H
—H
—Cl


H460 (a and b)
NH
—H
—H
—Br


H461 (a and b)
NH
—H
—H
—F


H462 (a and b)
NH
—H
—H
—CH3


H463 (a and b)
NH
—H
—H
—CF3


H464 (a and b)
NH
—H
—H
—OCH3


H465 (a and b)
NH
—H
—H
—OCH2CH3


H466 (a and b)
NH
—H
—H
—OCF3


H467 (a and b)
NH
—H
—H
-tert-butyl


H468 (a and b)
NH
—H
—H
-iso-propyl


H469 (a and b)
NH
—Cl
—Cl
—H


H470 (a and b)
NH
—Cl
—Br
—H


H471 (a and b)
NH
—Cl
—F
—H


H472 (a and b)
NH
—Cl
—CH3
—H


H473 (a and b)
NH
—Cl
—CF3
—H


H474 (a and b)
NH
—Cl
—OCH3
—H


H475 (a and b)
NH
—Cl
—OCH2CH3
—H


H476 (a and b)
NH
—Cl
—OCF3
—H


H477 (a and b)
NH
—Cl
-tert-butyl
—H


H478 (a and b)
NH
—Cl
-iso-propyl
—H


H479 (a and b)
NH
—Cl
—CH3
—CH3


H480 (a and b)
NH
—Cl
—H
—H


H481 (a and b)
NH
—Cl
—H
—Cl


H482 (a and b)
NH
—Cl
—H
—Br


H483 (a and b)
NH
—Cl
—H
—F


H484 (a and b)
NH
—Cl
—H
—CH3


H485 (a and b)
NH
—Cl
—H
—CF3


H486 (a and b)
NH
—Cl
—H
—OCH3


H487 (a and b)
NH
—Cl
—H
—OCH2CH3


H488 (a and b)
NH
—Cl
—H
—OCF3


H489 (a and b)
NH
—Cl
—H
-tert-butyl


H490 (a and b)
NH
—Cl
—H
-iso-propyl


H491 (a and b)
NH
—Cl
—H
—OCF3


H492 (a and b)
NH
—Cl
—H
-tert-butyl


H493 (a and b)
NH
—Cl
—H
-iso-propyl


H494 (a and b)
NH
—CH3
—Cl
—H


H495 (a and b)
NH
—CH3
—Br
—H


H496 (a and b)
NH
—CH3
—F
—H


H497 (a and b)
NH
—CH3
—CH3
—H


H498 (a and b)
NH
—CH3
—CF3
—H


H499 (a and b)
NH
—CH3
—OCH3
—H


H500 (a and b)
NH
—CH3
—OCH2CH3
—H


H501 (a and b)
NH
—CH3
—OCF3
—H


H502 (a and b)
NH
—CH3
-tert-butyl
—H


H503 (a and b)
NH
—CH3
-iso-propyl
—H


H504 (a and b)
NH
—CH3
—CH3
—CH3


H505 (a and b)
NH
—CH3
—H
—H


H506 (a and b)
NH
—CH3
—H
—Cl


H507 (a and b)
NH
—CH3
—H
—Br


H508 (a and b)
NH
—CH3
—H
—F


H509 (a and b)
NH
—CH3
—H
—CH3


H510 (a and b)
NH
—CH3
—H
—CF3


H511 (a and b)
NH
—CH3
—H
—OCH3


H512 (a and b)
NH
—CH3
—H
—OCH2CH3


H513 (a and b)
NH
—CH3
—H
—OCF3


H514 (a and b)
NH
—CH3
—H
-tert-butyl


H515 (a and b)
NH
—CH3
—H
-iso-propyl


H516 (a and b)
NH
—CF3
—Cl
—H


H517 (a and b)
NH
—CF3
—Br
—H


H518 (a and b)
NH
—CF3
—F
—H


H519 (a and b)
NH
—CF3
—CH3
—H


H520 (a and b)
NH
—CF3
—CF3
—H


H521 (a and b)
NH
—CF3
—OCH3
—H


H522 (a and b)
NH
—CF3
—OCH2CH3
—H


H523 (a and b)
NH
—CF3
—OCF3
—H


H524 (a and b)
NH
—CF3
-tert-butyl
—H


H525 (a and b)
NH
—CF3
-iso-propyl
—H


H526 (a and b)
NH
—CF3
—CH3
—CH3


H527 (a and b)
NH
—CF3
—H
—H


H528 (a and b)
NH
—CF3
—H
—Cl


H529 (a and b)
NH
—CF3
—H
—Br


H530 (a and b)
NH
—CF3
—H
—F


H531 (a and b)
NH
—CF3
—H
—CH3


H532 (a and b)
NH
—CF3
—H
—CF3


H533 (a and b)
NH
—CF3
—H
—OCH3


H534 (a and b)
NH
—CF3
—H
—OCH2CH3


H535 (a and b)
NH
—CF3
—H
—OCF3


H536 (a and b)
NH
—CF3
—H
-tert-butyl


H537 (a and b)
NH
—CF3
—H
-iso-propyl


H538 (a and b)
NH
—CHF2
—Cl
—H


H539 (a and b)
NH
—CHF2
—Br
—H


H540 (a and b)
NH
—CHF2
—F
—H


H541 (a and b)
NH
—CHF2
—CH3
—H


H542 (a and b)
NH
—CHF2
—CF3
—H


H543 (a and b)
NH
—CHF2
—OCH3
—H


H544 (a and b)
NH
—CHF2
—OCH2CH3
—H


H545 (a and b)
NH
—CHF2
—OCF3
—H


H546 (a and b)
NH
—CHF2
-tert-butyl
—H


H547 (a and b)
NH
—CHF2
-iso-propyl
—H


H548 (a and b)
NH
—CHF2
—CH3
—CH3


H549 (a and b)
NH
—CHF2
—H
—H


H550 (a and b)
NH
—CHF2
—H
—Cl


H551 (a and b)
NH
—CHF2
—H
—Br


H552 (a and b)
NH
—CHF2
—H
—F


H553 (a and b)
NH
—CHF2
—H
—CH3


H554 (a and b)
NH
—CHF2
—H
—CF3


H555 (a and b)
NH
—CHF2
—H
—OCH3


H556 (a and b)
NH
—CHF2
—H
—OCH2CH3


H557 (a and b)
NH
—CHF2
—H
—OCF3


H558 (a and b)
NH
—CHF2
—H
-tert-butyl


H559 (a and b)
NH
—CHF2
—H
-iso-propyl


H560 (a and b)
NH
—OH
—Cl
—H


H561 (a and b)
NH
—OH
—Br
—H


H562 (a and b)
NH
—OH
—F
—H


H563 (a and b)
NH
—OH
—CH3
—H


H564 (a and b)
NH
—OH
—CF3
—H


H565 (a and b)
NH
—OH
—OCH3
—H


H566 (a and b)
NH
—OH
—OCH2CH3
—H


H567 (a and b)
NH
—OH
—OCF3
—H


H568 (a and b)
NH
—OH
-tert-butyl
—H


H569 (a and b)
NH
—OH
-iso-propyl
—H


H570 (a and b)
NH
—OH
—CH3
—CH3


H571 (a and b)
NH
—OH
—H
—H


H572 (a and b)
NH
—OH
—H
—Cl


H573 (a and b)
NH
—OH
—H
—Br


H574 (a and b)
NH
—OH
—H
—F


H575 (a and b)
NH
—OH
—H
—CH3


H576 (a and b)
NH
—OH
—H
—CF3


H577 (a and b)
NH
—OH
—H
—OCH3


H578 (a and b)
NH
—OH
—H
—OCH2CH3


H579 (a and b)
NH
—OH
—H
—OCF3


H580 (a and b)
NH
—OH
—H
-tert-butyl


H581 (a and b)
NH
—OH
—H
-iso-propyl


H582 (a and b)
NH
—NO2
—Cl
—H


H583 (a and b)
NH
—NO2
—Br
—H


H584 (a and b)
NH
—NO2
—F
—H


H585 (a and b)
NH
—NO2
—CH3
—H


H586 (a and b)
NH
—NO2
—CF3
—H


H587 (a and b)
NH
—NO2
—OCH3
—H


H588 (a and b)
NH
—NO2
—OCH2CH3
—H


H589 (a and b)
NH
—NO2
—OCF3
—H


H590 (a and b)
NH
—NO2
-tert-butyl
—H


H591 (a and b)
NH
—NO2
-iso-propyl
—H


H592 (a and b)
NH
—NO2
—CH3
—CH3


H593 (a and b)
NH
—NO2
—H
—H


H594 (a and b)
NH
—NO2
—H
—Cl


H595 (a and b)
NH
—NO2
—H
—Br


H596 (a and b)
NH
—NO2
—H
—F


H597 (a and b)
NH
—NO2
—H
—CH3


H598 (a and b)
NH
—NO2
—H
—CF3


H599 (a and b)
NH
—NO2
—H
—OCH3


H600 (a and b)
NH
—NO2
—H
—OCH2CH3


H601 (a and b)
NH
—NO2
—H
—OCF3


H602 (a and b)
NH
—NO2
—H
-tert-butyl


H603 (a and b)
NH
—NO2
—H
-iso-propyl


H604 (a and b)
NH
—CN
—Br
—H


H605 (a and b)
NH
—CN
—Cl
—H


H606 (a and b)
NH
—CN
—F
—H


H607 (a and b)
NH
—CN
—CH3
—H


H608 (a and b)
NH
—CN
—CF3
—H


H609 (a and b)
NH
—CN
—OCH3
—H


H610 (a and b)
NH
—CN
—OCH2CH3
—H


H611 (a and b)
NH
—CN
—OCF3
—H


H612 (a and b)
NH
—CN
-tert-butyl
—H


H613 (a and b)
NH
—CN
-iso-propyl
—H


H614 (a and b)
NH
—CN
—CH3
—CH3


H615 (a and b)
NH
—CN
—H
—H


H616 (a and b)
NH
—CN
—H
—Cl


H617 (a and b)
NH
—CN
—H
—Br


H618 (a and b)
NH
—CN
—H
—F


H619 (a and b)
NH
—CN
—H
—CH3


H620 (a and b)
NH
—CN
—H
—CF3


H621 (a and b)
NH
—CN
—H
—OCH3


H622 (a and b)
NH
—CN
—H
—OCH2CH3


H623 (a and b)
NH
—CN
—H
—OCF3


H624 (a and b)
NH
—CN
—H
-tert-butyl


H625 (a and b)
NH
—CN
—H
-iso-propyl


H626 (a and b)
NH
—Br
—Br
—H


H627 (a and b)
NH
—Br
—Cl
—H


H628 (a and b)
NH
—Br
—F
—H


H629 (a and b)
NH
—Br
—CH3
—H


H630 (a and b)
NH
—Br
—CF3
—H


H631 (a and b)
NH
—Br
—OCH3
—H


H632 (a and b)
NH
—Br
—OCH2CH3
—H


H633 (a and b)
NH
—Br
—OCF3
—H


H634 (a and b)
NH
—Br
-tert-butyl
—H


H635 (a and b)
NH
—Br
-iso-propyl
—H


H636 (a and b)
NH
—Br
—CH3
—CH3


H637 (a and b)
NH
—Br
—H
—H


H638 (a and b)
NH
—Br
—H
—Cl


H639 (a and b)
NH
—Br
—H
—Br


H640 (a and b)
NH
—Br
—H
—F


H641 (a and b)
NH
—Br
—H
—CH3


H642 (a and b)
NH
—Br
—H
—CF3


H643 (a and b)
NH
—Br
—H
—OCH3


H644 (a and b)
NH
—Br
—H
—OCH2CH3


H645 (a and b)
NH
—Br
—H
—OCF3


H646 (a and b)
NH
—Br
—H
-tert-butyl


H647 (a and b)
NH
—Br
—H
-iso-propyl


H648 (a and b)
NH
—I
—Cl
—H


H649 (a and b)
NH
—I
—Br
—H


H650 (a and b)
NH
—I
—F
—H


H651 (a and b)
NH
—I
—CH3
—H


H652 (a and b)
NH
—I
—CF3
—H


H653 (a and b)
NH
—I
—OCH3
—H


H654 (a and b)
NH
—I
—OCH2CH3
—H


H655 (a and b)
NH
—I
—OCF3
—H


H656 (a and b)
NH
—I
-tert-butyl
—H


H657 (a and b)
NH
—I
-iso-propyl
—H


H658 (a and b)
NH
—I
—CH3
—CH3


H659 (a and b)
NH
—I
—H
—H


H660 (a and b)
NH
—I
—H
—Cl


H661 (a and b)
NH
—I
—H
—Br


H662 (a and b)
NH
—I
—H
—F


H663 (a and b)
NH
—I
—H
—CH3


H664 (a and b)
NH
—I
—H
—CF3


H665 (a and b)
NH
—I
—H
—OCH3


H666 (a and b)
NH
—I
—H
—OCH2CH3


H667 (a and b)
NH
—I
—H
—OCF3


H668 (a and b)
NH
—I
—H
-tert-butyl


H669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.













TABLE 9







(Ii)




embedded image




and pharmaceutically acceptable salts thereof, wherein:














Compound
R1
R8a







I01 (a and b)
—H
—H



I02 (a and b)
—H
-tert-butyl



I03 (a and b)
—H
-iso-butyl



I04 (a and b)
—H
-sec-butyl



I05 (a and b)
—H
-iso-propyl



I06 (a and b)
—H
-n-propyl



I07 (a and b)
—H
-cyclohexyl



I08 (a and b)
—H
-tert-butoxy



I09 (a and b)
—H
-isopropoxy



I10 (a and b)
—H
—CF3



I11 (a and b)
—H
—CH2CF3



I12 (a and b)
—H
—OCF3



I13 (a and b)
—H
—Cl



I14 (a and b)
—H
—Br



I15 (a and b)
—H
—I



I16 (a and b)
—H
-n-butyl



I17 (a and b)
—H
—CH3



I18 (a and b)
—H
—SCF3



I19 (a and b)
—H
—N(CH2CH3)2



I20 (a and b)
—H
—OCF2CHF2



I21 (a and b)
—H
—C(OH)(CF3)2



I22 (a and b)
—H
-(1,1-dimethyl-pentyl)



I23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



I24 (a and b)
—H
—N-piperidinyl



I25 (a and b)
—Cl
—H



I26 (a and b)
—Cl
-tert-butyl



I27 (a and b)
—Cl
-iso-butyl



I28 (a and b)
—Cl
-sec-butyl



I29 (a and b)
—Cl
-iso-propyl



I30 (a and b)
—Cl
-n-propyl



I31 (a and b)
—Cl
-cyclohexyl



I32 (a and b)
—Cl
-tert-butoxy



I33 (a and b)
—Cl
-isopropoxy



I34 (a and b)
—Cl
—CF3



I35 (a and b)
—Cl
—CH2CF3



I36 (a and b)
—Cl
—OCF3



I37 (a and b)
—Cl
—Cl



I38 (a and b)
—Cl
—Br



I39 (a and b)
—Cl
—I



I40 (a and b)
—Cl
-n-butyl



I41 (a and b)
—Cl
—CH3



I42 (a and b)
—Cl
—SCF3



I43 (a and b)
—Cl
—N(CH2CH3)2



I44 (a and b)
—Cl
—OCF2CHF2



I45 (a and b)
—Cl
—C(OH)(CF3)2



I46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



I47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



I48 (a and b)
—Cl
—N-piperidinyl



I49 (a and b)
—F
—H



I50 (a and b)
—F
-tert-butyl



I51 (a and b)
—F
-iso-butyl



I52 (a and b)
—F
-sec-butyl



I53 (a and b)
—F
-iso-propyl



I54 (a and b)
—F
-n-propyl



I55 (a and b)
—F
-cyclohexyl



I56 (a and b)
—F
-tert-butoxy



I57 (a and b)
—F
-isopropoxy



I58 (a and b)
—F
—CF3



I59 (a and b)
—F
—CH2CF3



I60 (a and b)
—F
—OCF3



I61 (a and b)
—F
—Cl



I62 (a and b)
—F
—Br



I63 (a and b)
—F
—I



I64 (a and b)
—F
-n-butyl



I65 (a and b)
—F
—CH3



I66 (a and b)
—F
—SCF3



I67 (a and b)
—F
—N(CH2CH3)2



I68 (a and b)
—F
—OCF2CHF2



I69 (a and b)
—F
—C(OH)(CF3)2



I70 (a and b)
—F
-(1,1-dimethyl-pentyl)



I71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



I72 (a and b)
—F
—N-piperidinyl



I73 (a and b)
—CH3
—H



I74 (a and b)
—CH3
-iso-butyl



I75 (a and b)
—CH3
-tert-butyl



I76 (a and b)
—CH3
-sec-butyl



I77 (a and b)
—CH3
-iso-propyl



I78 (a and b)
—CH3
-n-propyl



I79 (a and b)
—CH3
-cyclohexyl



I80 (a and b)
—CH3
-tert-butoxy



I81 (a and b)
—CH3
-isopropoxy



I82 (a and b)
—CH3
—CF3



I83 (a and b)
—CH3
—CH2CF3



I84 (a and b)
—CH3
—OCF3



I85 (a and b)
—CH3
—Cl



I86 (a and b)
—CH3
—Br



I87 (a and b)
—CH3
—I



I88 (a and b)
—CH3
-n-butyl



I89 (a and b)
—CH3
—CH3



I90 (a and b)
—CH3
—SCF3



I91 (a and b)
—CH3
—N(CH2CH3)2



I92 (a and b)
—CH3
—OCF2CHF2



I93 (a and b)
—CH3
—C(OH)(CF3)2



I94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



I95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



I96 (a and b)
—CH3
—N-piperidinyl



I97 (a and b)
—CF3
—H



I98 (a and b)
—CF3
-tert-butyl



I99 (a and b)
—CF3
-iso-butyl



I100 (a and b)
—CF3
-sec-butyl



I101 (a and b)
—CF3
-iso-propyl



I102 (a and b)
—CF3
-n-propyl



I103 (a and b)
—CF3
-cyclohexyl



I104 (a and b)
—CF3
-tert-butoxy



I105 (a and b)
—CF3
-isopropoxy



I106 (a and b)
—CF3
—CF3



I107 (a and b)
—CF3
—CH2CF3



I108 (a and b)
—CF3
—OCF3



I109 (a and b)
—CF3
—Cl



I110 (a and b)
—CF3
—Br



I111 (a and b)
—CF3
—I



I112 (a and b)
—CF3
-n-butyl



I113 (a and b)
—CF3
—CH3



I114 (a and b)
—CF3
—SCF3



I115 (a and b)
—CF3
—N(CH2CH3)2



I116 (a and b)
—CF3
—OCF2CHF2



I117 (a and b)
—CF3
—C(OH)(CF3)2



I118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



I119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



I120 (a and b)
—CF3
—N-piperidinyl



I121 (a and b)
—CHF2
-tert-butyl



I122 (a and b)
—CHF2
—H



I123 (a and b)
—CHF2
-iso-butyl



I124 (a and b)
—CHF2
-sec-butyl



I125 (a and b)
—CHF2
-iso-propyl



I126 (a and b)
—CHF2
-n-propyl



I127 (a and b)
—CHF2
-cyclohexyl



I128 (a and b)
—CHF2
-tert-butoxy



I129 (a and b)
—CHF2
-isopropoxy



I130 (a and b)
—CHF2
—CF3



I131 (a and b)
—CHF2
—CH2CF3



I132 (a and b)
—CHF2
—OCF3



I133 (a and b)
—CHF2
—Cl



I134 (a and b)
—CHF2
—Br



I135 (a and b)
—CHF2
—I



I136 (a and b)
—CHF2
-n-butyl



I137 (a and b)
—CHF2
—CH3



I138 (a and b)
—CHF2
—SCF3



I139 (a and b)
—CHF2
—N(CH2CH3)2



I140 (a and b)
—CHF2
—OCF2CHF2



I141 (a and b)
—CHF2
—C(OH)(CF3)2



I142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



I143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



I144 (a and b)
—CHF2
—N-piperidinyl



I145 (a and b)
—OH
—H



I146 (a and b)
—OH
-tert-butyl



I147 (a and b)
—OH
-iso-butyl



I148 (a and b)
—OH
-sec-butyl



I149 (a and b)
—OH
-iso-propyl



I150 (a and b)
—OH
-n-propyl



I151 (a and b)
—OH
-cyclohexyl



I152 (a and b)
—OH
-tert-butoxy



I153 (a and b)
—OH
-isopropoxy



I154 (a and b)
—OH
—CF3



I155 (a and b)
—OH
—CH2CF3



I156 (a and b)
—OH
—OCF3



I157 (a and b)
—OH
—Cl



I158 (a and b)
—OH
—Br



I159 (a and b)
—OH
—I



I160 (a and b)
—OH
-n-butyl



I161 (a and b)
—OH
—CH3



I162 (a and b)
—OH
—SCF3



I163 (a and b)
—OH
—N(CH2CH3)2



I164 (a and b)
—OH
—OCF2CHF2



I165 (a and b)
—OH
—C(OH)(CF3)2



I166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



I167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



I168 (a and b)
—OH
—N-piperidinyl



I169 (a and b)
—NO2
—H



I170 (a and b)
—NO2
-tert-butyl



I171 (a and b)
—NO2
-iso-butyl



I172 (a and b)
—NO2
-sec-butyl



I173 (a and b)
—NO2
-iso-propyl



I174 (a and b)
—NO2
-n-propyl



I175 (a and b)
—NO2
-cyclohexyl



I176 (a and b)
—NO2
-tert-butoxy



I177 (a and b)
—NO2
-isopropoxy



I178 (a and b)
—NO2
—CF3



I179 (a and b)
—NO2
—CH2CF3



I180 (a and b)
—NO2
—OCF3



I181 (a and b)
—NO2
—Cl



I182 (a and b)
—NO2
—Br



I183 (a and b)
—NO2
—I



I184 (a and b)
—NO2
-n-butyl



I185 (a and b)
—NO2
—CH3



I186 (a and b)
—NO2
—SCF3



I187 (a and b)
—NO2
—N(CH2CH3)2



I188 (a and b)
—NO2
—OCF2CHF2



I189 (a and b)
—NO2
—C(OH)(CF3)2



I190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



I191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



I192 (a and b)
—NO2
—N-piperidinyl



I193 (a and b)
—CN
—H



I194 (a and b)
—CN
-tert-butyl



I195 (a and b)
—CN
-iso-butyl



I196 (a and b)
—CN
-sec-butyl



I197 (a and b)
—CN
-iso-propyl



I198 (a and b)
—CN
-n-propyl



I199 (a and b)
—CN
-cyclohexyl



I200 (a and b)
—CN
-tert-butoxy



I201 (a and b)
—CN
-isopropoxy



I202 (a and b)
—CN
—CF3



I203 (a and b)
—CN
—CH2CF3



I204 (a and b)
—CN
—OCF3



I205 (a and b)
—CN
—Cl



I206 (a and b)
—CN
—Br



I207 (a and b)
—CN
—I



I208 (a and b)
—CN
-n-butyl



I209 (a and b)
—CN
—CH3



I210 (a and b)
—CN
—SCF3



I211 (a and b)
—CN
—N(CH2CH3)2



I212 (a and b)
—CN
—OCF2CHF2



I213 (a and b)
—CN
—C(OH)(CF3)2



I214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



I215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



I216 (a and b)
—CN
—N-piperidinyl



I217 (a and b)
—Br
—H



I218 (a and b)
—Br
-tert-butyl



I219 (a and b)
—Br
-iso-butyl



I220 (a and b)
—Br
-sec-butyl



I221 (a and b)
—Br
-iso-propyl



I222 (a and b)
—Br
-n-propyl



I223 (a and b)
—Br
-cyclohexyl



I224 (a and b)
—Br
-tert-butoxy



I225 (a and b)
—Br
-isopropoxy



I226 (a and b)
—Br
—CF3



I227 (a and b)
—Br
—CH2CF3



I228 (a and b)
—Br
—OCF3



I229 (a and b)
—Br
—Cl



I230 (a and b)
—Br
—Br



I231 (a and b)
—Br
—I



I232 (a and b)
—Br
-n-butyl



I233 (a and b)
—Br
—CH3



I234 (a and b)
—Br
—SCF3



I235 (a and b)
—Br
—N(CH2CH3)2



I236 (a and b)
—Br
—OCF2CHF2



I237 (a and b)
—Br
—C(OH)(CF3)2



I238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



I239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



I240 (a and b)
—Br
—N-piperidinyl



I241 (a and b)
—I
-tert-butyl



I242 (a and b)
—I
—H



I243 (a and b)
—I
-iso-butyl



I244 (a and b)
—I
-sec-butyl



I245 (a and b)
—I
-iso-propyl



I246 (a and b)
—I
-n-propyl



I247 (a and b)
—I
-cyclohexyl



I248 (a and b)
—I
-tert-butoxy



I249 (a and b)
—I
-isopropoxy



I250 (a and b)
—I
—CF3



I251 (a and b)
—I
—CH2CF3



I252 (a and b)
—I
—OCF3



I253 (a and b)
—I
—Cl



I254 (a and b)
—I
—Br



I255 (a and b)
—I
—I



I256 (a and b)
—I
-n-butyl



I257 (a and b)
—I
—CH3



I258 (a and b)
—I
—SCF3



I259 (a and b)
—I
—N(CH2CH3)2



I260 (a and b)
—I
—OCF2CHF2



I261 (a and b)
—I
—C(OH)(CF3)2



I262 (a and b)
—I
-(1,1-dimethyl-pentyl)



I263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



I264 (a and b)
—I
—N-piperidinyl







(a) means that R3 is —H.



(b) means that R3 is —CH3.













TABLE 10







(Ij)




embedded image




and pharmaceutically acceptable salts thereof, wherein:














Compound
Y
R1
(R8)a
(R8)b





J1 (a and b)
S
—H
—Cl
—H


J2 (a and b)
S
—H
—Br
—H


J3 (a and b)
S
—H
—F
—H


J4 (a and b)
S
—H
—CH3
—H


J5 (a and b)
S
—H
—CF3
—H


J6 (a and b)
S
—H
—OCH3
—H


J7 (a and b)
S
—H
—OCH2CH3
—H


J8 (a and b)
S
—H
—OCF3
—H


J9 (a and b)
S
—H
-tert-butyl
—H


J10 (a and b)
S
—H
-iso-propyl
—H


J11 (a and b)
S
—H
—CH3
—CH3


J12 (a and b)
S
—H
—H
—H


J13 (a and b)
S
—H
—H
—Cl


J14 (a and b)
S
—H
—H
—Br


J15 (a and b)
S
—H
—H
—F


J16 (a and b)
S
—H
—H
—CH3


J17 (a and b)
S
—H
—H
—CF3


J18 (a and b)
S
—H
—H
—OCH3


J19 (a and b)
S
—H
—H
—OCH2CH3


J20 (a and b)
S
—H
—H
—OCF3


J21 (a and b)
S
—H
—H
-tert-butyl


J22 (a and b)
S
—H
—H
-iso-propyl


J23 (a and b)
S
—Cl
—Cl
—H


J24 (a and b)
S
—Cl
—Br
—H


J25 (a and b)
S
—Cl
—F
—H


J26 (a and b)
S
—Cl
—CH3
—H


J27 (a and b)
S
—Cl
—CF3
—H


J28 (a and b)
S
—Cl
—OCH3
—H


J29 (a and b)
S
—Cl
—OCH2CH3
—H


J30 (a and b)
S
—Cl
—OCF3
—H


J31 (a and b)
S
—Cl
-tert-butyl
—H


J32 (a and b)
S
—Cl
-iso-propyl
—H


J33 (a and b)
S
—Cl
—CH3
—CH3


J34 (a and b)
S
—Cl
—H
—H


J35 (a and b)
S
—Cl
—H
—Cl


J36 (a and b)
S
—Cl
—H
—Br


J37 (a and b)
S
—Cl
—H
—F


J38 (a and b)
S
—Cl
—H
—CH3


J39 (a and b)
S
—Cl
—H
—CF3


J40 (a and b)
S
—Cl
—H
—OCH3


J41 (a and b)
S
—Cl
—H
—OCH2CH3


J42 (a and b)
S
—Cl
—H
—OCF3


J43 (a and b)
S
—Cl
—H
-tert-butyl


J44 (a and b)
S
—Cl
—H
-iso-propyl


J45 (a and b)
S
—Cl
—H
—OCF3


J46 (a and b)
S
—Cl
—H
-tert-butyl


J47 (a and b)
S
—Cl
—H
-iso-propyl


J48 (a and b)
S
—CH3
—Cl
—H


J49 (a and b)
S
—CH3
—Br
—H


J50 (a and b)
S
—CH3
—F
—H


J51 (a and b)
S
—CH3
—CH3
—H


J52 (a and b)
S
—CH3
—CF3
—H


J53 (a and b)
S
—CH3
—OCH3
—H


J54 (a and b)
S
—CH3
—OCH2CH3
—H


J55 (a and b)
S
—CH3
—OCF3
—H


J56 (a and b)
S
—CH3
-tert-butyl
—H


J57 (a and b)
S
—CH3
-iso-propyl
—H


J58 (a and b)
S
—CH3
—CH3
—CH3


J59 (a and b)
S
—CH3
—H
—H


J60 (a and b)
S
—CH3
—H
—Cl


J61 (a and b)
S
—CH3
—H
—Br


J62 (a and b)
S
—CH3
—H
—F


J63 (a and b)
S
—CH3
—H
—CH3


J64 (a and b)
S
—CH3
—H
—CF3


J65 (a and b)
S
—CH3
—H
—OCH3


J66 (a and b)
S
—CH3
—H
—OCH2CH3


J67 (a and b)
S
—CH3
—H
—OCF3


J68 (a and b)
S
—CH3
—H
-tert-butyl


J69 (a and b)
S
—CH3
—H
-iso-propyl


J70 (a and b)
S
—CF3
—Cl
—H


J71 (a and b)
S
—CF3
—Br
—H


J72 (a and b)
S
—CF3
—F
—H


J73 (a and b)
S
—CF3
—CH3
—H


J74 (a and b)
S
—CF3
—CF3
—H


J75 (a and b)
S
—CF3
—OCH3
—H


J76 (a and b)
S
—CF3
—OCH2CH3
—H


J77 (a and b)
S
—CF3
—OCF3
—H


J78 (a and b)
S
—CF3
-tert-butyl
—H


J79 (a and b)
S
—CF3
-iso-propyl
—H


J80 (a and b)
S
—CF3
—CH3
—CH3


J81 (a and b)
S
—CF3
—H
—H


J82 (a and b)
S
—CF3
—H
—Cl


J83 (a and b)
S
—CF3
—H
—Br


J84 (a and b)
S
—CF3
—H
—F


J85 (a and b)
S
—CF3
—H
—CH3


J86 (a and b)
S
—CF3
—H
—CF3


J87 (a and b)
S
—CF3
—H
—OCH3


J88 (a and b)
S
—CF3
—H
—OCH2CH3


J89 (a and b)
S
—CF3
—H
—OCF3


J90 (a and b)
S
—CF3
—H
-tert-butyl


J91 (a and b)
S
—CF3
—H
-iso-propyl


J92 (a and b)
S
—CHF2
—Cl
—H


J93 (a and b)
S
—CHF2
—Br
—H


J94 (a and b)
S
—CHF2
—F
—H


J95 (a and b)
S
—CHF2
—CH3
—H


J96 (a and b)
S
—CHF2
—CF3
—H


J97 (a and b)
S
—CHF2
—OCH3
—H


J98 (a and b)
S
—CHF2
—OCH2CH3
—H


J99 (a and b)
S
—CHF2
—OCF3
—H


J100 (a and b)
S
—CHF2
-tert-butyl
—H


J101 (a and b)
S
—CHF2
-iso-propyl
—H


J102 (a and b)
S
—CHF2
—CH3
—CH3


J103 (a and b)
S
—CHF2
—H
—H


J104 (a and b)
S
—CHF2
—H
—Cl


J105 (a and b)
S
—CHF2
—H
—Br


J106 (a and b)
S
—CHF2
—H
—F


J107 (a and b)
S
—CHF2
—H
—CH3


J108 (a and b)
S
—CHF2
—H
—CF3


J109 (a and b)
S
—CHF2
—H
—OCH3


J110 (a and b)
S
—CHF2
—H
—OCH2CH3


J111 (a and b)
S
—CHF2
—H
—OCF3


J112 (a and b)
S
—CHF2
—H
-tert-butyl


J113 (a and b)
S
—CHF2
—H
-iso-propyl


J114 (a and b)
S
—OH
—Cl
—H


J115 (a and b)
S
—OH
—Br
—H


J116 (a and b)
S
—OH
—F
—H


J117 (a and b)
S
—OH
—CH3
—H


J118 (a and b)
S
—OH
—CF3
—H


J119 (a and b)
S
—OH
—OCH3
—H


J120 (a and b)
S
—OH
—OCH2CH3
—H


J121 (a and b)
S
—OH
—OCF3
—H


J122 (a and b)
S
—OH
-tert-butyl
—H


J123 (a and b)
S
—OH
-iso-propyl
—H


J124 (a and b)
S
—OH
—CH3
—CH3


J125 (a and b)
S
—OH
—H
—H


J126 (a and b)
S
—OH
—H
—Cl


J127 (a and b)
S
—OH
—H
—Br


J128 (a and b)
S
—OH
—H
—F


J129 (a and b)
S
—OH
—H
—CH3


J130 (a and b)
S
—OH
—H
—CF3


J131 (a and b)
S
—OH
—H
—OCH3


J132 (a and b)
S
—OH
—H
—OCH2CH3


J133 (a and b)
S
—OH
—H
—OCF3


J134 (a and b)
S
—OH
—H
-tert-butyl


J135 (a and b)
S
—OH
—H
-iso-propyl


J136 (a and b)
S
—NO2
—Cl
—H


J137 (a and b)
S
—NO2
—Br
—H


J138 (a and b)
S
—NO2
—F
—H


J139 (a and b)
S
—NO2
—CH3
—H


J140 (a and b)
S
—NO2
—CF3
—H


J141 (a and b)
S
—NO2
—OCH3
—H


J142 (a and b)
S
—NO2
—OCH2CH3
—H


J143 (a and b)
S
—NO2
—OCF3
—H


J144 (a and b)
S
—NO2
-tert-butyl
—H


J145 (a and b)
S
—NO2
-iso-propyl
—H


J146 (a and b)
S
—NO2
—CH3
—CH3


J147 (a and b)
S
—NO2
—H
—H


J148 (a and b)
S
—NO2
—H
—Cl


J149 (a and b)
S
—NO2
—H
—Br


J150 (a and b)
S
—NO2
—H
—F


J151 (a and b)
S
—NO2
—H
—CH3


J152 (a and b)
S
—NO2
—H
—CF3


J153 (a and b)
S
—NO2
—H
—OCH3


J154 (a and b)
S
—NO2
—H
—OCH2CH3


J155 (a and b)
S
—NO2
—H
—OCF3


J156 (a and b)
S
—NO2
—H
-tert-butyl


J157 (a and b)
S
—NO2
—H
-iso-propyl


J158 (a and b)
S
—CN
—Br
—H


J159 (a and b)
S
—CN
—Cl
—H


J160 (a and b)
S
—CN
—F
—H


J161 (a and b)
S
—CN
—CH3
—H


J162 (a and b)
S
—CN
—CF3
—H


J163 (a and b)
S
—CN
—OCH3
—H


J164 (a and b)
S
—CN
—OCH2CH3
—H


J165 (a and b)
S
—CN
—OCF3
—H


J166 (a and b)
S
—CN
-tert-butyl
—H


J167 (a and b)
S
—CN
-iso-propyl
—H


J168 (a and b)
S
—CN
—CH3
—CH3


J169 (a and b)
S
—CN
—H
—H


J170 (a and b)
S
—CN
—H
—Cl


J171 (a and b)
S
—CN
—H
—Br


J172 (a and b)
S
—CN
—H
—F


J173 (a and b)
S
—CN
—H
—CH3


J174 (a and b)
S
—CN
—H
—CF3


J175 (a and b)
S
—CN
—H
—OCH3


J176 (a and b)
S
—CN
—H
—OCH2CH3


J177 (a and b)
S
—CN
—H
—OCF3


J178 (a and b)
S
—CN
—H
-tert-butyl


J179 (a and b)
S
—CN
—H
-iso-propyl


J180 (a and b)
S
—Br
—Br
—H


J181 (a and b)
S
—Br
—Cl
—H


J182 (a and b)
S
—Br
—F
—H


J183 (a and b)
S
—Br
—CH3
—H


J184 (a and b)
S
—Br
—CF3
—H


J185 (a and b)
S
—Br
—OCH3
—H


J186 (a and b)
S
—Br
—OCH2CH3
—H


J187 (a and b)
S
—Br
—OCF3
—H


J188 (a and b)
S
—Br
-tert-butyl
—H


J189 (a and b)
S
—Br
-iso-propyl
—H


J190 (a and b)
S
—Br
—CH3
—CH3


J191 (a and b)
S
—Br
—H
—H


J192 (a and b)
S
—Br
—H
—Cl


J193 (a and b)
S
—Br
—H
—Br


J194 (a and b)
S
—Br
—H
—F


J195 (a and b)
S
—Br
—H
—CH3


J196 (a and b)
S
—Br
—H
—CF3


J197 (a and b)
S
—Br
—H
—OCH3


J198 (a and b)
S
—Br
—H
—OCH2CH3


J199 (a and b)
S
—Br
—H
—OCF3


J200 (a and b)
S
—Br
—H
-tert-butyl


J201 (a and b)
S
—Br
—H
-iso-propyl


J202 (a and b)
S
—I
—Cl
—H


J203 (a and b)
S
—I
—Br
—H


J204 (a and b)
S
—I
—F
—H


J205 (a and b)
S
—I
—CH3
—H


J206 (a and b)
S
—I
—CF3
—H


J207 (a and b)
S
—I
—OCH3
—H


J208 (a and b)
S
—I
—OCH2CH3
—H


J209 (a and b)
S
—I
—OCF3
—H


J210 (a and b)
S
—I
-tert-butyl
—H


J211 (a and b)
S
—I
-iso-propyl
—H


J212 (a and b)
S
—I
—CH3
—CH3


J213 (a and b)
S
—I
—H
—H


J214 (a and b)
S
—I
—H
—Cl


J215 (a and b)
S
—I
—H
—Br


J216 (a and b)
S
—I
—H
—F


J217 (a and b)
S
—I
—H
—CH3


J218 (a and b)
S
—I
—H
—CF3


J219 (a and b)
S
—I
—H
—OCH3


J220 (a and b)
S
—I
—H
—OCH2CH3


J221 (a and b)
S
—I
—H
—OCF3


J222 (a and b)
S
—I
—H
-tert-butyl


J223 (a and b)
S
—I
—H
-iso-propyl


J224 (a and b)
O
—H
—Cl
—H


J225 (a and b)
O
—H
—Br
—H


J226 (a and b)
O
—H
—F
—H


J227 (a and b)
O
—H
—CH3
—H


J228 (a and b)
O
—H
—CF3
—H


J229 (a and b)
O
—H
—OCH3
—H


J230 (a and b)
O
—H
—OCH2CH3
—H


J231 (a and b)
O
—H
—OCF3
—H


J232 (a and b)
O
—H
-tert-butyl
—H


J233 (a and b)
O
—H
-iso-propyl
—H


J234 (a and b)
O
—H
—CH3
—CH3


J235 (a and b)
O
—H
—H
—H


J236 (a and b)
O
—H
—H
—Cl


J237 (a and b)
O
—H
—H
—Br


J238 (a and b)
O
—H
—H
—F


J239 (a and b)
O
—H
—H
—CH3


J240 (a and b)
O
—H
—H
—CF3


J241 (a and b)
O
—H
—H
—OCH3


J242 (a and b)
O
—H
—H
—OCH2CH3


J243 (a and b)
O
—H
—H
—OCF3


J244 (a and b)
O
—H
—H
-tert-butyl


J245 (a and b)
O
—H
—H
-iso-propyl


J246 (a and b)
O
—Cl
—Cl
—H


J247 (a and b)
O
—Cl
—Br
—H


J248 (a and b)
O
—Cl
—F
—H


J249 (a and b)
O
—Cl
—CH3
—H


J250 (a and b)
O
—Cl
—CF3
—H


J251 (a and b)
O
—Cl
—OCH3
—H


J252 (a and b)
O
—Cl
—OCH2CH3
—H


J253 (a and b)
O
—Cl
—OCF3
—H


J254 (a and b)
O
—Cl
-tert-butyl
—H


J255 (a and b)
O
—Cl
-iso-propyl
—H


J256 (a and b)
O
—Cl
—CH3
—CH3


J257 (a and b)
O
—Cl
—H
—H


J258 (a and b)
O
—Cl
—H
—Cl


J259 (a and b)
O
—Cl
—H
—Br


J260 (a and b)
O
—Cl
—H
—F


J261 (a and b)
O
—Cl
—H
—CH3


J262 (a and b)
O
—Cl
—H
—CF3


J263 (a and b)
O
—Cl
—H
—OCH3


J264 (a and b)
O
—Cl
—H
—OCH2CH3


J265 (a and b)
O
—Cl
—H
—OCF3


J266 (a and b)
O
—Cl
—H
-tert-butyl


J267 (a and b)
O
—Cl
—H
-iso-propyl


J268 (a and b)
O
—Cl
—H
—OCF3


J269 (a and b)
O
—Cl
—H
-tert-butyl


J270 (a and b)
O
—Cl
—H
-iso-propyl


J271 (a and b)
O
—CH3
—Cl
—H


J272 (a and b)
O
—CH3
—Br
—H


J273 (a and b)
O
—CH3
—F
—H


J274 (a and b)
O
—CH3
—CH3
—H


J275 (a and b)
O
—CH3
—CF3
—H


J276 (a and b)
O
—CH3
—OCH3
—H


J277 (a and b)
O
—CH3
—OCH2CH3
—H


J278 (a and b)
O
—CH3
—OCF3
—H


J279 (a and b)
O
—CH3
-tert-butyl
—H


J280 (a and b)
O
—CH3
-iso-propyl
—H


J281 (a and b)
O
—CH3
—CH3
—CH3


J282 (a and b)
O
—CH3
—H
—H


J283 (a and b)
O
—CH3
—H
—Cl


J284 (a and b)
O
—CH3
—H
—Br


J285 (a and b)
O
—CH3
—H
—F


J286 (a and b)
O
—CH3
—H
—CH3


J287 (a and b)
O
—CH3
—H
—CF3


J288 (a and b)
O
—CH3
—H
—OCH3


J289 (a and b)
O
—CH3
—H
—OCH2CH3


J290 (a and b)
O
—CH3
—H
—OCF3


J291 (a and b)
O
—CH3
—H
-tert-butyl


J292 (a and b)
O
—CH3
—H
-iso-propyl


J293 (a and b)
O
—CF3
—Cl
—H


J294 (a and b)
O
—CF3
—Br
—H


J295 (a and b)
O
—CF3
—F
—H


J296 (a and b)
O
—CF3
—CH3
—H


J297 (a and b)
O
—CF3
—CF3
—H


J298 (a and b)
O
—CF3
—OCH3
—H


J299 (a and b)
O
—CF3
—OCH2CH3
—H


J300 (a and b)
O
—CF3
—OCF3
—H


J301 (a and b)
O
—CF3
-tert-butyl
—H


J302 (a and b)
O
—CF3
-iso-propyl
—H


J303 (a and b)
O
—CF3
—CH3
—CH3


J304 (a and b)
O
—CF3
—H
—H


J305 (a and b)
O
—CF3
—H
—Cl


J306 (a and b)
O
—CF3
—H
—Br


J307 (a and b)
O
—CF3
—H
—F


J308 (a and b)
O
—CF3
—H
—CH3


J309 (a and b)
O
—CF3
—H
—CF3


J310 (a and b)
O
—CF3
—H
—OCH3


J311 (a and b)
O
—CF3
—H
—OCH2CH3


J312 (a and b)
O
—CF3
—H
—OCF3


J313 (a and b)
O
—CF3
—H
-tert-butyl


J314 (a and b)
O
—CF3
—H
-iso-propyl


J315 (a and b)
O
—CHF2
—Cl
—H


J316 (a and b)
O
—CHF2
—Br
—H


J317 (a and b)
O
—CHF2
—F
—H


J318 (a and b)
O
—CHF2
—CH3
—H


J319 (a and b)
O
—CHF2
—CF3
—H


J320 (a and b)
O
—CHF2
—OCH3
—H


J321 (a and b)
O
—CHF2
—OCH2CH3
—H


J322 (a and b)
O
—CHF2
—OCF3
—H


J323 (a and b)
O
—CHF2
-tert-butyl
—H


J324 (a and b)
O
—CHF2
-iso-propyl
—H


J325 (a and b)
O
—CHF2
—CH3
—CH3


J326 (a and b)
O
—CHF2
—H
—H


J327 (a and b)
O
—CHF2
—H
—Cl


J328 (a and b)
O
—CHF2
—H
—Br


J329 (a and b)
O
—CHF2
—H
—F


J330 (a and b)
O
—CHF2
—H
—CH3


J331 (a and b)
O
—CHF2
—H
—CF3


J332 (a and b)
O
—CHF2
—H
—OCH3


J333 (a and b)
O
—CHF2
—H
—OCH2CH3


J334 (a and b)
O
—CHF2
—H
—OCF3


J335 (a and b)
O
—CHF2
—H
-tert-butyl


J336 (a and b)
O
—CHF2
—H
-iso-propyl


J337 (a and b)
O
—OH
—Cl
—H


J338 (a and b)
O
—OH
—Br
—H


J339 (a and b)
O
—OH
—F
—H


J340 (a and b)
O
—OH
—CH3
—H


J341 (a and b)
O
—OH
—CF3
—H


J342 (a and b)
O
—OH
—OCH3
—H


J343 (a and b)
O
—OH
—OCH2CH3
—H


J344 (a and b)
O
—OH
—OCF3
—H


J345 (a and b)
O
—OH
-tert-butyl
—H


J346 (a and b)
O
—OH
-iso-propyl
—H


J347 (a and b)
O
—OH
—CH3
—CH3


J348 (a and b)
O
—OH
—H
—H


J349 (a and b)
O
—OH
—H
—Cl


J350 (a and b)
O
—OH
—H
—Br


J351 (a and b)
O
—OH
—H
—F


J352 (a and b)
O
—OH
—H
—CH3


J353 (a and b)
O
—OH
—H
—CF3


J354 (a and b)
O
—OH
—H
—OCH3


J355 (a and b)
O
—OH
—H
—OCH2CH3


J356 (a and b)
O
—OH
—H
—OCF3


J357 (a and b)
O
—OH
—H
-tert-butyl


J358 (a and b)
O
—OH
—H
-iso-propyl


J359 (a and b)
O
—NO2
—Cl
—H


J360 (a and b)
O
—NO2
—Br
—H


J361 (a and b)
O
—NO2
—F
—H


J362 (a and b)
O
—NO2
—CH3
—H


J363 (a and b)
O
—NO2
—CF3
—H


J364 (a and b)
O
—NO2
—OCH3
—H


J365 (a and b)
O
—NO2
—OCH2CH3
—H


J366 (a and b)
O
—NO2
—OCF3
—H


J367 (a and b)
O
—NO2
-tert-butyl
—H


J368 (a and b)
O
—NO2
-iso-propyl
—H


J369 (a and b)
O
—NO2
—CH3
—CH3


J370 (a and b)
O
—NO2
—H
—H


J371 (a and b)
O
—NO2
—H
—Cl


J372 (a and b)
O
—NO2
—H
—Br


J373 (a and b)
O
—NO2
—H
—F


J374 (a and b)
O
—NO2
—H
—CH3


J375 (a and b)
O
—NO2
—H
—CF3


J376 (a and b)
O
—NO2
—H
—OCH3


J377 (a and b)
O
—NO2
—H
—OCH2CH3


J378 (a and b)
O
—NO2
—H
—OCF3


J379 (a and b)
O
—NO2
—H
-tert-butyl


J380 (a and b)
O
—NO2
—H
-iso-propyl


J381 (a and b)
O
—CN
—Br
—H


J382 (a and b)
O
—CN
—Cl
—H


J383 (a and b)
O
—CN
—F
—H


J384 (a and b)
O
—CN
—CH3
—H


J385 (a and b)
O
—CN
—CF3
—H


J386 (a and b)
O
—CN
—OCH3
—H


J387 (a and b)
O
—CN
—OCH2CH3
—H


J388 (a and b)
O
—CN
—OCF3
—H


J389 (a and b)
O
—CN
-tert-butyl
—H


J390 (a and b)
O
—CN
-iso-propyl
—H


J391 (a and b)
O
—CN
—CH3
—CH3


J392 (a and b)
O
—CN
—H
—H


J393 (a and b)
O
—CN
—H
—Cl


J394 (a and b)
O
—CN
—H
—Br


J395 (a and b)
O
—CN
—H
—F


J396 (a and b)
O
—CN
—H
—CH3


J397 (a and b)
O
—CN
—H
—CF3


J398 (a and b)
O
—CN
—H
—OCH3


J399 (a and b)
O
—CN
—H
—OCH2CH3


J400 (a and b)
O
—CN
—H
—OCF3


J401 (a and b)
O
—CN
—H
-tert-butyl


J402 (a and b)
O
—CN
—H
-iso-propyl


J403 (a and b)
O
—Br
—Br
—H


J404 (a and b)
O
—Br
—Cl
—H


J405 (a and b)
O
—Br
—F
—H


J406 (a and b)
O
—Br
—CH3
—H


J407 (a and b)
O
—Br
—CF3
—H


J408 (a and b)
O
—Br
—OCH3
—H


J409 (a and b)
O
—Br
—OCH2CH3
—H


J410 (a and b)
O
—Br
—OCF3
—H


J411 (a and b)
O
—Br
-tert-butyl
—H


J412 (a and b)
O
—Br
-iso-propyl
—H


J413 (a and b)
O
—Br
—CH3
—CH3


J414 (a and b)
O
—Br
—H
—H


J415 (a and b)
O
—Br
—H
—Cl


J416 (a and b)
O
—Br
—H
—Br


J417 (a and b)
O
—Br
—H
—F


J418 (a and b)
O
—Br
—H
—CH3


J419 (a and b)
O
—Br
—H
—CF3


J420 (a and b)
O
—Br
—H
—OCH3


J421 (a and b)
O
—Br
—H
—OCH2CH3


J422 (a and b)
O
—Br
—H
—OCF3


J423 (a and b)
O
—Br
—H
-tert-butyl


J424 (a and b)
O
—Br
—H
-iso-propyl


J425 (a and b)
O
—I
—Cl
—H


J426 (a and b)
O
—I
—Br
—H


J427 (a and b)
O
—I
—F
—H


J428 (a and b)
O
—I
—CH3
—H


J429 (a and b)
O
—I
—CF3
—H


J430 (a and b)
O
—I
—OCH3
—H


J431 (a and b)
O
—I
—OCH2CH3
—H


J432 (a and b)
O
—I
—OCF3
—H


J433 (a and b)
O
—I
-tert-butyl
—H


J434 (a and b)
O
—I
-iso-propyl
—H


J435 (a and b)
O
—I
—CH3
—CH3


J436 (a and b)
O
—I
—H
—H


J437 (a and b)
O
—I
—H
—Cl


J438 (a and b)
O
—I
—H
—Br


J439 (a and b)
O
—I
—H
—F


J440 (a and b)
O
—I
—H
—CH3


J441 (a and b)
O
—I
—H
—CF3


J442 (a and b)
O
—I
—H
—OCH3


J443 (a and b)
O
—I
—H
—OCH2CH3


J444 (a and b)
O
—I
—H
—OCF3


J445 (a and b)
O
—I
—H
-tert-butyl


J446 (a and b)
O
—I
—H
-iso-propyl


J447 (a and b)
NH
—H
—Cl
—H


J448 (a and b)
NH
—H
—Br
—H


J449 (a and b)
NH
—H
—F
—H


J450 (a and b)
NH
—H
—CH3
—H


J451 (a and b)
NH
—H
—CF3
—H


J452 (a and b)
NH
—H
—OCH3
—H


J453 (a and b)
NH
—H
—OCH2CH3
—H


J454 (a and b)
NH
—H
—OCF3
—H


J455 (a and b)
NH
—H
-tert-butyl
—H


J456 (a and b)
NH
—H
-iso-propyl
—H


J457 (a and b)
NH
—H
—CH3
—CH3


J458 (a and b)
NH
—H
—H
—H


J459 (a and b)
NH
—H
—H
—Cl


J460 (a and b)
NH
—H
—H
—Br


J461 (a and b)
NH
—H
—H
—F


J462 (a and b)
NH
—H
—H
—CH3


J463 (a and b)
NH
—H
—H
—CF3


J464 (a and b)
NH
—H
—H
—OCH3


J465 (a and b)
NH
—H
—H
—OCH2CH3


J466 (a and b)
NH
—H
—H
—OCF3


J467 (a and b)
NH
—H
—H
-tert-butyl


J468 (a and b)
NH
—H
—H
-iso-propyl


J469 (a and b)
NH
—Cl
—Cl
—H


J470 (a and b)
NH
—Cl
—Br
—H


J471 (a and b)
NH
—Cl
—F
—H


J472 (a and b)
NH
—Cl
—CH3
—H


J473 (a and b)
NH
—Cl
—CF3
—H


J474 (a and b)
NH
—Cl
—OCH3
—H


J475 (a and b)
NH
—Cl
—OCH2CH3
—H


J476 (a and b)
NH
—Cl
—OCF3
—H


J477 (a and b)
NH
—Cl
-tert-butyl
—H


J478 (a and b)
NH
—Cl
-iso-propyl
—H


J479 (a and b)
NH
—Cl
—CH3
—CH3


J480 (a and b)
NH
—Cl
—H
—H


J481 (a and b)
NH
—Cl
—H
—Cl


J482 (a and b)
NH
—Cl
—H
—Br


J483 (a and b)
NH
—Cl
—H
—F


J484 (a and b)
NH
—Cl
—H
—CH3


J485 (a and b)
NH
—Cl
—H
—CF3


J486 (a and b)
NH
—Cl
—H
—OCH3


J487 (a and b)
NH
—Cl
—H
—OCH2CH3


J488 (a and b)
NH
—Cl
—H
—OCF3


J489 (a and b)
NH
—Cl
—H
-tert-butyl


J490 (a and b)
NH
—Cl
—H
-iso-propyl


J491 (a and b)
NH
—Cl
—H
—OCF3


J492 (a and b)
NH
—Cl
—H
-tert-butyl


J493 (a and b)
NH
—Cl
—H
-iso-propyl


J494 (a and b)
NH
—CH3
—Cl
—H


J495 (a and b)
NH
—CH3
—Br
—H


J496 (a and b)
NH
—CH3
—F
—H


J497 (a and b)
NH
—CH3
—CH3
—H


J498 (a and b)
NH
—CH3
—CF3
—H


J499 (a and b)
NH
—CH3
—OCH3
—H


J500 (a and b)
NH
—CH3
—OCH2CH3
—H


J501 (a and b)
NH
—CH3
—OCF3
—H


J502 (a and b)
NH
—CH3
-tert-butyl
—H


J503 (a and b)
NH
—CH3
-iso-propyl
—H


J504 (a and b)
NH
—CH3
—CH3
—CH3


J505 (a and b)
NH
—CH3
—H
—H


J506 (a and b)
NH
—CH3
—H
—Cl


J507 (a and b)
NH
—CH3
—H
—Br


J508 (a and b)
NH
—CH3
—H
—F


J509 (a and b)
NH
—CH3
—H
—CH3


J510 (a and b)
NH
—CH3
—H
—CF3


J511 (a and b)
NH
—CH3
—H
—OCH3


J512 (a and b)
NH
—CH3
—H
—OCH2CH3


J513 (a and b)
NH
—CH3
—H
—OCF3


J514 (a and b)
NH
—CH3
—H
-tert-butyl


J515 (a and b)
NH
—CH3
—H
-iso-propyl


J516 (a and b)
NH
—CF3
—Cl
—H


J517 (a and b)
NH
—CF3
—Br
—H


J518 (a and b)
NH
—CF3
—F
—H


J519 (a and b)
NH
—CF3
—CH3
—H


J520 (a and b)
NH
—CF3
—CF3
—H


J521 (a and b)
NH
—CF3
—OCH3
—H


J522 (a and b)
NH
—CF3
—OCH2CH3
—H


J523 (a and b)
NH
—CF3
—OCF3
—H


J524 (a and b)
NH
—CF3
-tert-butyl
—H


J525 (a and b)
NH
—CF3
-iso-propyl
—H


J526 (a and b)
NH
—CF3
—CH3
—CH3


J527 (a and b)
NH
—CF3
—H
—H


J528 (a and b)
NH
—CF3
—H
—Cl


J529 (a and b)
NH
—CF3
—H
—Br


J530 (a and b)
NH
—CF3
—H
—F


J531 (a and b)
NH
—CF3
—H
—CH3


J532 (a and b)
NH
—CF3
—H
—CF3


J533 (a and b)
NH
—CF3
—H
—OCH3


J534 (a and b)
NH
—CF3
—H
—OCH2CH3


J535 (a and b)
NH
—CF3
—H
—OCF3


J536 (a and b)
NH
—CF3
—H
-tert-butyl


J537 (a and b)
NH
—CF3
—H
-iso-propyl


J538 (a and b)
NH
—CHF2
—Cl
—H


J539 (a and b)
NH
—CHF2
—Br
—H


J540 (a and b)
NH
—CHF2
—F
—H


J541 (a and b)
NH
—CHF2
—CH3
—H


J542 (a and b)
NH
—CHF2
—CF3
—H


J543 (a and b)
NH
—CHF2
—OCH3
—H


J544 (a and b)
NH
—CHF2
—OCH2CH3
—H


J545 (a and b)
NH
—CHF2
—OCF3
—H


J546 (a and b)
NH
—CHF2
-tert-butyl
—H


J547 (a and b)
NH
—CHF2
-iso-propyl
—H


J548 (a and b)
NH
—CHF2
—CH3
—CH3


J549 (a and b)
NH
—CHF2
—H
—H


J550 (a and b)
NH
—CHF2
—H
—Cl


J551 (a and b)
NH
—CHF2
—H
—Br


J552 (a and b)
NH
—CHF2
—H
—F


J553 (a and b)
NH
—CHF2
—H
—CH3


J554 (a and b)
NH
—CHF2
—H
—CF3


J555 (a and b)
NH
—CHF2
—H
—OCH3


J556 (a and b)
NH
—CHF2
—H
—OCH2CH3


J557 (a and b)
NH
—CHF2
—H
—OCF3


J558 (a and b)
NH
—CHF2
—H
-tert-butyl


J559 (a and b)
NH
—CHF2
—H
-iso-propyl


J560 (a and b)
NH
—OH
—Cl
—H


J561 (a and b)
NH
—OH
—Br
—H


J562 (a and b)
NH
—OH
—F
—H


J563 (a and b)
NH
—OH
—CH3
—H


J564 (a and b)
NH
—OH
—CF3
—H


J565 (a and b)
NH
—OH
—OCH3
—H


J566 (a and b)
NH
—OH
—OCH2CH3
—H


J567 (a and b)
NH
—OH
—OCF3
—H


J568 (a and b)
NH
—OH
-tert-butyl
—H


J569 (a and b)
NH
—OH
-iso-propyl
—H


J570 (a and b)
NH
—OH
—CH3
—CH3


J571 (a and b)
NH
—OH
—H
—H


J572 (a and b)
NH
—OH
—H
—Cl


J573 (a and b)
NH
—OH
—H
—Br


J574 (a and b)
NH
—OH
—H
—F


J575 (a and b)
NH
—OH
—H
—CH3


J576 (a and b)
NH
—OH
—H
—CF3


J577 (a and b)
NH
—OH
—H
—OCH3


J578 (a and b)
NH
—OH
—H
—OCH2CH3


J579 (a and b)
NH
—OH
—H
—OCF3


J580 (a and b)
NH
—OH
—H
-tert-butyl


J581 (a and b)
NH
—OH
—H
-iso-propyl


J582 (a and b)
NH
—NO2
—Cl
—H


J583 (a and b)
NH
—NO2
—Br
—H


J584 (a and b)
NH
—NO2
—F
—H


J585 (a and b)
NH
—NO2
—CH3
—H


J586 (a and b)
NH
—NO2
—CF3
—H


J587 (a and b)
NH
—NO2
—OCH3
—H


J588 (a and b)
NH
—NO2
—OCH2CH3
—H


J589 (a and b)
NH
—NO2
—OCF3
—H


J590 (a and b)
NH
—NO2
-tert-butyl
—H


J591 (a and b)
NH
—NO2
-iso-propyl
—H


J592 (a and b)
NH
—NO2
—CH3
—CH3


J593 (a and b)
NH
—NO2
—H
—H


J594 (a and b)
NH
—NO2
—H
—Cl


J595 (a and b)
NH
—NO2
—H
—Br


J596 (a and b)
NH
—NO2
—H
—F


J597 (a and b)
NH
—NO2
—H
—CH3


J598 (a and b)
NH
—NO2
—H
—CF3


J599 (a and b)
NH
—NO2
—H
—OCH3


J600 (a and b)
NH
—NO2
—H
—OCH2CH3


J601 (a and b)
NH
—NO2
—H
—OCF3


J602 (a and b)
NH
—NO2
—H
-tert-butyl


J603 (a and b)
NH
—NO2
—H
-iso-propyl


J604 (a and b)
NH
—CN
—Br
—H


J605 (a and b)
NH
—CN
—Cl
—H


J606 (a and b)
NH
—CN
—F
—H


J607 (a and b)
NH
—CN
—CH3
—H


J608 (a and b)
NH
—CN
—CF3
—H


J609 (a and b)
NH
—CN
—OCH3
—H


J610 (a and b)
NH
—CN
—OCH2CH3
—H


J611 (a and b)
NH
—CN
—OCF3
—H


J612 (a and b)
NH
—CN
-tert-butyl
—H


J613 (a and b)
NH
—CN
-iso-propyl
—H


J614 (a and b)
NH
—CN
—CH3
—CH3


J615 (a and b)
NH
—CN
—H
—H


J616 (a and b)
NH
—CN
—H
—Cl


J617 (a and b)
NH
—CN
—H
—Br


J618 (a and b)
NH
—CN
—H
—F


J619 (a and b)
NH
—CN
—H
—CH3


J620 (a and b)
NH
—CN
—H
—CF3


J621 (a and b)
NH
—CN
—H
—OCH3


J622 (a and b)
NH
—CN
—H
—OCH2CH3


J623 (a and b)
NH
—CN
—H
—OCF3


J624 (a and b)
NH
—CN
—H
-tert-butyl


J625 (a and b)
NH
—CN
—H
-iso-propyl


J626 (a and b)
NH
—Br
—Br
—H


J627 (a and b)
NH
—Br
—Cl
—H


J628 (a and b)
NH
—Br
—F
—H


J629 (a and b)
NH
—Br
—CH3
—H


J630 (a and b)
NH
—Br
—CF3
—H


J631 (a and b)
NH
—Br
—OCH3
—H


J632 (a and b)
NH
—Br
—OCH2CH3
—H


J633 (a and b)
NH
—Br
—OCF3
—H


J634 (a and b)
NH
—Br
-tert-butyl
—H


J635 (a and b)
NH
—Br
-iso-propyl
—H


J636 (a and b)
NH
—Br
—CH3
—CH3


J637 (a and b)
NH
—Br
—H
—H


J638 (a and b)
NH
—Br
—H
—Cl


J639 (a and b)
NH
—Br
—H
—Br


J640 (a and b)
NH
—Br
—H
—F


J641 (a and b)
NH
—Br
—H
—CH3


J642 (a and b)
NH
—Br
—H
—CF3


J643 (a and b)
NH
—Br
—H
—OCH3


J644 (a and b)
NH
—Br
—H
—OCH2CH3


J645 (a and b)
NH
—Br
—H
—OCF3


J646 (a and b)
NH
—Br
—H
-tert-butyl


J647 (a and b)
NH
—Br
—H
-iso-propyl


J648 (a and b)
NH
—I
—Cl
—H


J649 (a and b)
NH
—I
—Br
—H


J650 (a and b)
NH
—I
—F
—H


J651 (a and b)
NH
—I
—CH3
—H


J652 (a and b)
NH
—I
—CF3
—H


J653 (a and b)
NH
—I
—OCH3
—H


J654 (a and b)
NH
—I
—OCH2CH3
—H


J655 (a and b)
NH
—I
—OCF3
—H


J656 (a and b)
NH
—I
-tert-butyl
—H


J657 (a and b)
NH
—I
-iso-propyl
—H


J658 (a and b)
NH
—I
—CH3
—CH3


J659 (a and b)
NH
—I
—H
—H


J660 (a and b)
NH
—I
—H
—Cl


J661 (a and b)
NH
—I
—H
—Br


J662 (a and b)
NH
—I
—H
—F


J663 (a and b)
NH
—I
—H
—CH3


J664 (a and b)
NH
—I
—H
—CF3


J665 (a and b)
NH
—I
—H
—OCH3


J666 (a and b)
NH
—I
—H
—OCH2CH3


J667 (a and b)
NH
—I
—H
—OCF3


J668 (a and b)
NH
—I
—H
-tert-butyl


J669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.













TABLE 11







(Ik)




embedded image







and pharmaceutically acceptable salts thereof, wherein:










Compound
Ar1







K1 (a and b)
-2-(3-chloropyridyl)



K2 (a and b)
-2-(3-fluoropyridyl)



K3 (a and b)
-2-(3-methylpyridyl)



K4 (a and b)
-2-(3-CF3-pyridyl)



K5 (a and b)
-2-(3-CHF2-pyridyl)



K6 (a and b)
-2-(3-hydroxypyridyl)



K7 (a and b)
-2-(3-nitropyridyl)



K8 (a and b)
-2-(3-cyanopyridyl)



K9 (a and b)
-2-(3-bromopyridyl)



K10 (a and b)
-2-(3-iodopyridyl)



K11 (a and b)
-4-(5-chloropyrimidinyl)



K12 (a and b)
-4-(5-methylpyrimidinyl)



K13 (a and b)
-4-(5-fluoropyrimidinyl)



K14 (a and b)
-2-(3-chloropyrazinyl)



K15 (a and b)
-2-(3-methylpyrazinyl)



K16 (a and b)
-2-(3-fluoropyrazinyl)



K17 (a and b)
-3-(4-chloropyridazinyl)



K18 (a and b)
-3-(4-methylpyridazinyl)



K19 (a and b)
-3-(4-fluoropyridazinyl)



K20 (a and b)
-5-(4-chlorothiadiazolyl)



K21 (a and b)
-5-(4-methylthiadiazolyl)



K22 (a and b)
-5-(4-fluorothiadiazolyl)







(a) means that R3 is —H.



(b) means that R3 is —CH3.













TABLE 12







(Il)




embedded image







and pharmaceutically acceptable salts thereof, wherein:












Compound
Ar1
R8a
R8b






L1 (a and b)
-2-(3-chloropyridyl)
—Cl
—CF3



L2 (a and b)
-2-(3-chloropyridyl)
—CF3
—Cl



L3 (a and b)
-2-(3-chloropyridyl)
—CH3
—CF3



L4 (a and b)
-2-(3-chloropyridyl)
—SCF3
—Cl



L5 (a and b)
-2-(3-chloropyridyl)
—F
—CF3



L6 (a and b)
-2-(3-chloropyridyl)
—CF3
—F



L7 (a and b)
-2-(3-chloropyridyl)
—CN
—CF3



L8 (a and b)
-2-(3-chloropyridyl)
—OCF3
—Cl



L9 (a and b)
-2-(3-fluoropyridyl)
—Cl
—CF3



L10 (a and b)
-2-(3-fluoropyridyl)
—CF3
—Cl



L11 (a and b)
-2-(3-fluoropyridyl)
—CH3
—CF3



L12 (a and b)
-2-(3-fluoropyridyl)
—SCF3
—Cl



L13 (a and b)
-2-(3-fluoropyridyl)
—F
—CF3



L14 (a and b)
-2-(3-fluoropyridyl)
—CF3
—F



L15 (a and b)
-2-(3-fluoropyridyl)
—CN
—CF3



L16 (a and b)
-2-(3-fluoropyridyl)
—OCF3
—Cl



L17 (a and b)
-2-(3-methylpyridyl)
—Cl
—CF3



L18 (a and b)
-2-(3-methylpyridyl)
—CF3
—Cl



L19 (a and b)
-2-(3-methylpyridyl)
—CH3
—CF3



L20 (a and b)
-2-(3-methylpyridyl)
—SCF3
—Cl



L21 (a and b)
-2-(3-methylpyridyl)
—F
—CF3



L22 (a and b)
-2-(3-methylpyridyl)
—CF3
—F



L23 (a and b)
-2-(3-methylpyridyl)
—CN
—CF3



L24 (a and b)
-2-(3-methylpyridyl)
—OCF3
—Cl



L25 (a and b)
-2-(3-CF3-pyridyl)
—Cl
—CF3



L26 (a and b)
-2-(3-CF3-pyridyl)
—CF3
—Cl



L27 (a and b)
-2-(3-CF3-pyridyl)
—CH3
—CF3



L28 (a and b)
-2-(3-CF3-pyridyl)
—SCF3
—Cl



L29 (a and b)
-2-(3-CF3-pyridyl)
—F
—CF3



L30 (a and b)
-2-(3-CF3-pyridyl)
—CF3
—F



L31 (a and b)
-2-(3-CF3-pyridyl)
—CN
—CF3



L32 (a and b)
-2-(3-CF3-pyridyl)
—OCF3
—Cl



L33 (a and b)
-2-(3-CHF2-pyridyl)
—Cl
—CF3



L34 (a and b)
-2-(3-CHF2-pyridyl)
—CF3
—Cl



L35 (a and b)
-2-(3-CHF2-pyridyl)
—CH3
—CF3



L36 (a and b)
-2-(3-CHF2-pyridyl)
—SCF3
—Cl



L37 (a and b)
-2-(3-CHF2-pyridyl)
—F
—CF3



L38 (a and b)
-2-(3-CHF2-pyridyl)
—CF3
—F



L39 (a and b)
-2-(3-CHF2-pyridyl)
—CN
—CF3



L40 (a and b)
-2-(3-CHF2-pyridyl)
—OCF3
—Cl



L41 (a and b)
-2-(3-hydroxypyridyl)
—Cl
—CF3



L42 (a and b)
-2-(3-hydroxypyridyl)
—CF3
—Cl



L43 (a and b)
-2-(3-hydroxypyridyl)
—CH3
—CF3



L44 (a and b)
-2-(3-hydroxypyridyl)
—SCF3
—Cl



L45 (a and b)
-2-(3-hydroxypyridyl)
—F
—CF3



L46 (a and b)
-2-(3-hydroxypyridyl)
—CF3
—F



L47 (a and b)
-2-(3-hydroxypyridyl)
—CN
—CF3



L48 (a and b)
-2-(3-hydroxypyridyl)
—OCF3
—Cl



L49 (a and b)
-2-(3-nitropyridyl)
—Cl
—CF3



L50 (a and b)
-2-(3-nitropyridyl)
—CF3
—Cl



L51 (a and b)
-2-(3-nitropyridyl)
—CH3
—CF3



L52 (a and b)
-2-(3-nitropyridyl)
—SCF3
—Cl



L53 (a and b)
-2-(3-nitropyridyl)
—F
—CF3



L54 (a and b)
-2-(3-nitropyridyl)
—CF3
—F



L55 (a and b)
-2-(3-nitropyridyl)
—CN
—CF3



L56 (a and b)
-2-(3-nitropyridyl)
—OCF3
—Cl



L57 (a and b)
-2-(3-cyanopyridyl)
—Cl
—CF3



L58 (a and b)
-2-(3-cyanopyridyl)
—CF3
—Cl



L59 (a and b)
-2-(3-cyanopyridyl)
—CH3
—CF3



L60 (a and b)
-2-(3-cyanopyridyl)
—SCF3
—Cl



L61 (a and b)
-2-(3-cyanopyridyl)
—F
—CF3



L62 (a and b)
-2-(3-cyanopyridyl)
—CF3
—F



L63 (a and b)
-2-(3-cyanopyridyl)
—CN
—CF3



L64 (a and b)
-2-(3-cyanopyridyl)
—OCF3
—Cl



L65 (a and b)
-2-(3-bromopyridyl)
—Cl
—CF3



L66 (a and b)
-2-(3-bromopyridyl)
—CF3
—Cl



L67 (a and b)
-2-(3-bromopyridyl)
—CH3
—CF3



L68 (a and b)
-2-(3-bromopyridyl)
—SCF3
—Cl



L69 (a and b)
-2-(3-bromopyridyl)
—F
—CF3



L70 (a and b)
-2-(3-bromopyridyl)
—CF3
—F



L71 (a and b)
-2-(3-bromopyridyl)
—CN
—CF3



L72 (a and b)
-2-(3-bromopyridyl)
—OCF3
—Cl



L73 (a and b)
-2-(3-iodopyridyl)
—Cl
—CF3



L74 (a and b)
-2-(3-iodopyridyl)
—CF3
—Cl



L75 (a and b)
-2-(3-iodopyridyl)
—CH3
—CF3



L76 (a and b)
-2-(3-iodopyridyl)
—SCF3
—Cl



L77 (a and b)
-2-(3-iodopyridyl)
—F
—CF3



L78 (a and b)
-2-(3-iodopyridyl)
—CF3
—F



L79 (a and b)
-2-(3-iodopyridyl)
—CN
—CF3



L80 (a and b)
-2-(3-iodopyridyl)
—OCF3
—Cl



L81 (a and b)
-4-(5-chloropyrimidinyl)
—Cl
—CF3



L82 (a and b)
-4-(5-chloropyrimidinyl)
—CF3
—Cl



L83 (a and b)
-4-(5-chloropyrimidinyl)
—CH3
—CF3



L84 (a and b)
-4-(5-chloropyrimidinyl)
—SCF3
—Cl



L85 (a and b)
-4-(5-chloropyrimidinyl)
—F
—CF3



L86 (a and b)
-4-(5-chloropyrimidinyl)
—CF3
—F



L87 (a and b)
-4-(5-chloropyrimidinyl)
—CN
—CF3



L88 (a and b)
-4-(5-chloropyrimidinyl)
—OCF3
—Cl



L89 (a and b)
-4-(5-methylpyrimidinyl)
—Cl
—CF3



L90 (a and b)
-4-(5-methylpyrimidinyl)
—CF3
—Cl



L91 (a and b)
-4-(5-methylpyrimidinyl)
—CH3
—CF3



L92 (a and b)
-4-(5-methylpyrimidinyl)
—SCF3
—Cl



L93 (a and b)
-4-(5-methylpyrimidinyl)
—F
—CF3



L94 (a and b)
-4-(5-methylpyrimidinyl)
—CF3
—F



L95 (a and b)
-4-(5-methylpyrimidinyl)
—CN
—CF3



L96 (a and b)
-4-(5-methylpyrimidinyl)
—OCF3
—Cl



L97 (a and b)
-4-(5-fluoropyrimidinyl)
—Cl
—CF3



L98 (a and b)
-4-(5-fluoropyrimidinyl)
—CF3
—Cl



L99 (a and b)
-4-(5-fluoropyrimidinyl)
—CH3
—CF3



L100 (a and b)
-4-(5-fluoropyrimidinyl)
—SCF3
—Cl



L101 (a and b)
-4-(5-fluoropyrimidinyl)
—F
—CF3



L102 (a and b)
-4-(5-fluoropyrimidinyl)
—CF3
—F



L103 (a and b)
-4-(5-fluoropyrimidinyl)
—CN
—CF3



L104 (a and b)
-4-(5-fluoropyrimidinyl)
—OCF3
—Cl



L105 (a and b)
-2-(3-chloropyrazinyl)
—Cl
—CF3



L106 (a and b)
-2-(3-chloropyrazinyl)
—CF3
—Cl



L107 (a and b)
-2-(3-chloropyrazinyl)
—CH3
—CF3



L108 (a and b)
-2-(3-chloropyrazinyl)
—SCF3
—Cl



L109 (a and b)
-2-(3-chloropyrazinyl)
—F
—CF3



L110 (a and b)
-2-(3-chloropyrazinyl)
—CF3
—F



L111 (a and b)
-2-(3-chloropyrazinyl)
—CN
—CF3



L112 (a and b)
-2-(3-chloropyrazinyl)
—OCF3
—Cl



L113 (a and b)
-2-(3-methylpyrazinyl)
—Cl
—CF3



L114 (a and b)
-2-(3-methylpyrazinyl)
—CF3
—Cl



L115 (a and b)
-2-(3-methylpyrazinyl)
—CH3
—CF3



L116 (a and b)
-2-(3-methylpyrazinyl)
—SCF3
—Cl



L117 (a and b)
-2-(3-methylpyrazinyl)
—F
—CF3



L118 (a and b)
-2-(3-methylpyrazinyl)
—CF3
—F



L119 (a and b)
-2-(3-methylpyrazinyl)
—CN
—CF3



L120 (a and b)
-2-(3-methylpyrazinyl)
—OCF3
—Cl



L121 (a and b)
-2-(3-fluoropyrazinyl)
—Cl
—CF3



L122 (a and b)
-2-(3-fluoropyrazinyl)
—CF3
—Cl



L123 (a and b)
-2-(3-fluoropyrazinyl)
—CH3
—CF3



L124 (a and b)
-2-(3-fluoropyrazinyl)
—SCF3
—Cl



L125 (a and b)
-2-(3-fluoropyrazinyl)
—F
—CF3



L126 (a and b)
-2-(3-fluoropyrazinyl)
—CF3
—F



L127 (a and b)
-2-(3-fluoropyrazinyl)
—CN
—CF3



L128 (a and b)
-2-(3-fluoropyrazinyl)
—OCF3
—Cl



L129 (a and b)
-3-(4-chloropyridazinyl)
—Cl
—CF3



L130 (a and b)
-3-(4-chloropyridazinyl)
—CF3
—Cl



L131 (a and b)
-3-(4-chloropyridazinyl)
—CH3
—CF3



L132 (a and b)
-3-(4-chloropyridazinyl)
—SCF3
—Cl



L133 (a and b)
-3-(4-chloropyridazinyl)
—F
—CF3



L134 (a and b)
-3-(4-chloropyridazinyl)
—CF3
—F



L135 (a and b)
-3-(4-chloropyridazinyl)
—CN
—CF3



L136 (a and b)
-3-(4-chloropyridazinyl)
—OCF3
—Cl



L137 (a and b)
-3-(4-methylpyridazinyl)
—Cl
—CF3



L138 (a and b)
-3-(4-methylpyridazinyl)
—CF3
—Cl



L139 (a and b)
-3-(4-methylpyridazinyl)
—CH3
—CF3



L140 (a and b)
-3-(4-methylpyridazinyl)
—SCF3
—Cl



L141 (a and b)
-3-(4-methylpyridazinyl)
—F
—CF3



L142 (a and b)
-3-(4-methylpyridazinyl)
—CF3
—F



L143 (a and b)
-3-(4-methylpyridazinyl)
—CN
—CF3



L144 (a and b)
-3-(4-methylpyridazinyl)
—OCF3
—Cl



L145 (a and b)
-3-(4-fluoropyridazinyl)
—Cl
—CF3



L146 (a and b)
-3-(4-fluoropyridazinyl)
—CF3
—Cl



L147 (a and b)
-3-(4-fluoropyridazinyl)
—CH3
—CF3



L148 (a and b)
-3-(4-fluoropyridazinyl)
—SCF3
—Cl



L149 (a and b)
-3-(4-fluoropyridazinyl)
—F
—CF3



L150 (a and b)
-3-(4-fluoropyridazinyl)
—CF3
—F



L151 (a and b)
-3-(4-fluoropyridazinyl)
—CN
—CF3



L152 (a and b)
-3-(4-fluoropyridazinyl)
—OCF3
—Cl



L153 (a and b)
-5-(4-chlorothiadiazolyl)
—Cl
—CF3



L154 (a and b)
-5-(4-chlorothiadiazolyl)
—CF3
—Cl



L155 (a and b)
-5-(4-chlorothiadiazolyl)
—CH3
—CF3



L156 (a and b)
-5-(4-chlorothiadiazolyl)
—SCF3
—Cl



L157 (a and b)
-5-(4-chlorothiadiazolyl)
—F
—CF3



L158 (a and b)
-5-(4-chlorothiadiazolyl)
—CF3
—F



L159 (a and b)
-5-(4-chlorothiadiazolyl)
—CN
—CF3



L160 (a and b)
-5-(4-chlorothiadiazolyl)
—OCF3
—Cl



L161 (a and b)
-5-(4-methylthiadiazolyl)
—Cl
—CF3



L162 (a and b)
-5-(4-methylthiadiazolyl)
—CF3
—Cl



L163 (a and b)
-5-(4-methylthiadiazolyl)
—CH3
—CF3



L164 (a and b)
-5-(4-methylthiadiazolyl)
—SCF3
—Cl



L165 (a and b)
-5-(4-methylthiadiazolyl)
—F
—CF3



L166 (a and b)
-5-(4-methylthiadiazolyl)
—CF3
—F



L167 (a and b)
-5-(4-methylthiadiazolyl)
—CN
—CF3



L168 (a and b)
-5-(4-methylthiadiazolyl)
—OCF3
—Cl



L169 (a and b)
-5-(4-fluorothiadiazolyl)
—Cl
—CF3



L170 (a and b)
-5-(4-fluorothiadiazolyl)
—CF3
—Cl



L171 (a and b)
-5-(4-fluorothiadiazolyl)
—CH3
—CF3



L172 (a and b)
-5-(4-fluorothiadiazolyl)
—SCF3
—Cl



L173 (a and b)
-5-(4-fluorothiadiazolyl)
—F
—CF3



L174 (a and b)
-5-(4-fluorothiadiazolyl)
—CF3
—F



L175 (a and b)
-5-(4-fluorothiadiazolyl)
—CN
—CF3



L176 (a and b)
-5-(4-fluorothiadiazolyl)
—OCF3
—Cl





(a) means that R3 is —H.


(b) means that R3 is —CH3.













TABLE 13







(Im)




embedded image







and pharmaceutically acceptable salts thereof, wherein:











Compound
Ar1
Z1
Z2
R8a





M1 (a and b)
-2-(3-chloropyridyl)
N
CH
—CF3


M2 (a and b)
-2-(3-fluoropyridyl)
N
CH
—CF3


M3 (a and b)
-2-(3-methylpyridyl)
N
CH
—CF3


M4 (a and b)
-2-(3-CF3-pyridyl)
N
CH
—CF3


M5 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
—CF3


M6 (a and b)
-2-(3-hydroxypyridyl)
N
CH
—CF3


M7 (a and b)
-2-(3-nitropyridyl)
N
CH
—CF3


M8 (a and b)
-2-(3-cyanopyridyl)
N
CH
—CF3


M9 (a and b)
-2-(3-bromopyridyl)
N
CH
—CF3


M10 (a and b)
-2-(3-iodopyridyl)
N
CH
—CF3


M11 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
—CF3


M12 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
—CF3


M13 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
—CF3


M14 (a and b)
-2-(3-chloropyrazinyl)
N
CH
—CF3


M15 (a and b)
-2-(3-methylpyrazinyl)
N
CH
—CF3


M16 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
—CF3


M17 (a and b)
-3-(4-chloropyridazinyl)
N
CH
—CF3


M18 (a and b)
-3-(4-methylpyridazinyl)
N
CH
—CF3


M19 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
—CF3


M20 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
—CF3


M21 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—CF3


M22 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
—CF3


M23 (a and b)
-2-(3-chloropyridyl)
CH
N
—CF3


M24 (a and b)
-2-(3-fluoropyridyl)
CH
N
—CF3


M25 (a and b)
-2-(3-methylpyridyl)
CH
N
—CF3


M26 (a and b)
-2-(3-CF3-pyridyl)
CH
N
—CF3


M27 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
—CF3


M28 (a and b)
-2-(3-hydroxypyridyl)
CH
N
—CF3


M29 (a and b)
-2-(3-nitropyridyl)
CH
N
—CF3


M30 (a and b)
-2-(3-cyanopyridyl)
CH
N
—CF3


M31 (a and b)
-2-(3-bromopyridyl)
CH
N
—CF3


M32 (a and b)
-2-(3-iodopyridyl)
CH
N
—CF3


M33 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
—CF3


M34 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
—CF3


M35 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
—CF3


M36 (a and b)
-2-(3-chloropyrazinyl)
CH
N
—CF3


M37 (a and b)
-2-(3-methylpyrazinyl)
CH
N
—CF3


M38 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
—CF3


M39 (a and b)
-3-(4-chloropyridazinyl)
CH
N
—CF3


M40 (a and b)
-3-(4-methylpyridazinyl)
CH
N
—CF3


M41 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
—CF3


M42 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
—CF3


M43 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—CF3


M44 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
—CF3


M45 (a and b)
-2-(3-chloropyridyl)
N
CH
-tert-butyl


M46 (a and b)
-2-(3-fluoropyridyl)
N
CH
-tert-butyl


M47 (a and b)
-2-(3-methylpyridyl)
N
CH
-tert-butyl


M48 (a and b)
-2-(3-CF3-pyridyl)
N
CH
-tert-butyl


M49 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
-tert-butyl


M50 (a and b)
-2-(3-hydroxypyridyl)
N
CH
-tert-butyl


M51 (a and b)
-2-(3-nitropyridyl)
N
CH
-tert-butyl


M52 (a and b)
-2-(3-cyanopyridyl)
N
CH
-tert-butyl


M53 (a and b)
-2-(3-bromopyridyl)
N
CH
-tert-butyl


M54 (a and b)
-2-(3-iodopyridyl)
N
CH
-tert-butyl


M55 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
-tert-butyl


M56 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
-tert-butyl


M57 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
-tert-butyl


M58 (a and b)
-2-(3-chloropyrazinyl)
N
CH
-tert-butyl


M59 (a and b)
-2-(3-methylpyrazinyl)
N
CH
-tert-butyl


M60 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
-tert-butyl


M61 (a and b)
-3-(4-chloropyridazinyl)
N
CH
-tert-butyl


M62 (a and b)
-3-(4-methylpyridazinyl)
N
CH
-tert-butyl


M63 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
-tert-butyl


M64 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
-tert-butyl


M65 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-tert-butyl


M66 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
-tert-butyl


M67 (a and b)
-2-(3-chloropyridyl)
CH
N
-tert-butyl


M68 (a and b)
-2-(3-fluoropyridyl)
CH
N
-tert-butyl


M69 (a and b)
-2-(3-methylpyridyl)
CH
N
-tert-butyl


M70 (a and b)
-2-(3-CF3-pyridyl)
CH
N
-tert-butyl


M71 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
-tert-butyl


M72 (a and b)
-2-(3-hydroxypyridyl)
CH
N
-tert-butyl


M73 (a and b)
-2-(3-nitropyridyl)
CH
N
-tert-butyl


M74 (a and b)
-2-(3-cyanopyridyl)
CH
N
-tert-butyl


M75 (a and b)
-2-(3-bromopyridyl)
CH
N
-tert-butyl


M76 (a and b)
-2-(3-iodopyridyl)
CH
N
-tert-butyl


M77 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
-tert-butyl


M78 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
-tert-butyl


M79 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
-tert-butyl


M80 (a and b)
-2-(3-chloropyrazinyl)
CH
N
-tert-butyl


M81 (a and b)
-2-(3-methylpyrazinyl)
CH
N
-tert-butyl


M82 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
-tert-butyl


M83 (a and b)
-3-(4-chloropyridazinyl)
CH
N
-tert-butyl


M84 (a and b)
-3-(4-methylpyridazinyl)
CH
N
-tert-butyl


M85 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
-tert-butyl


M86 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
-tert-butyl


M87 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-tert-butyl


M88 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
-tert-butyl


M89 (a and b)
-2-(3-chloropyridyl)
N
CH
-iso-butyl


M90 (a and b)
-2-(3-fluoropyridyl)
N
CH
-iso-butyl


M91 (a and b)
-2-(3-methylpyridyl)
N
CH
-iso-butyl


M92 (a and b)
-2-(3-CF3-pyridyl)
N
CH
-iso-butyl


M93 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
-iso-butyl


M94 (a and b)
-2-(3-hydroxypyridyl)
N
CH
-iso-butyl


M95 (a and b)
-2-(3-nitropyridyl)
N
CH
-iso-butyl


M96 (a and b)
-2-(3-cyanopyridyl)
N
CH
-iso-butyl


M97 (a and b)
-2-(3-bromopyridyl)
N
CH
-iso-butyl


M98 (a and b)
-2-(3-iodopyridyl)
N
CH
-iso-butyl


M99 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
-iso-butyl


M100 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
-iso-butyl


M101 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
-iso-butyl


M102 (a and b)
-2-(3-chloropyrazinyl)
N
CH
-iso-butyl


M103 (a and b)
-2-(3-methylpyrazinyl)
N
CH
-iso-butyl


M104 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
-iso-butyl


M105 (a and b)
-3-(4-chloropyridazinyl)
N
CH
-iso-butyl


M106 (a and b)
-3-(4-methylpyridazinyl)
N
CH
-iso-butyl


M107 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
-iso-butyl


M108 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
-iso-butyl


M109 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-iso-butyl


M110 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
-iso-butyl


M111 (a and b)
-2-(3-chloropyridyl)
CH
N
-iso-butyl


M112 (a and b)
-2-(3-fluoropyridyl)
CH
N
-iso-butyl


M113 (a and b)
-2-(3-methylpyridyl)
CH
N
-iso-butyl


M114 (a and b)
-2-(3-CF3-pyridyl)
CH
N
-iso-butyl


M115 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
-iso-butyl


M116 (a and b)
-2-(3-hydroxypyridyl)
CH
N
-iso-butyl


M117 (a and b)
-2-(3-nitropyridyl)
CH
N
-iso-butyl


M118 (a and b)
-2-(3-cyanopyridyl)
CH
N
-iso-butyl


M119 (a and b)
-2-(3-bromopyridyl)
CH
N
-iso-butyl


M120 (a and b)
-2-(3-iodopyridyl)
CH
N
-iso-butyl


M121 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
-iso-butyl


M122 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
-iso-butyl


M123 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
-iso-butyl


M124 (a and b)
-2-(3-chloropyrazinyl)
CH
N
-iso-butyl


M125 (a and b)
-2-(3-methylpyrazinyl)
CH
N
-iso-butyl


M126 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
-iso-butyl


M127 (a and b)
-3-(4-chloropyridazinyl)
CH
N
-iso-butyl


M128 (a and b)
-3-(4-methylpyridazinyl)
CH
N
-iso-butyl


M129 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
-iso-butyl


M130 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
-iso-butyl


M131 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-iso-butyl


M132 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
-iso-butyl


M133 (a and b)
-2-(3-chloropyridyl)
N
CH
-sec-butyl


M134 (a and b)
-2-(3-fluoropyridyl)
N
CH
-sec-butyl


M135 (a and b)
-2-(3-methylpyridyl)
N
CH
-sec-butyl


M136 (a and b)
-2-(3-CF3-pyridyl)
N
CH
-sec-butyl


M137 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
-sec-butyl


M138 (a and b)
-2-(3-hydroxypyridyl)
N
CH
-sec-butyl


M139 (a and b)
-2-(3-nitropyridyl)
N
CH
-sec-butyl


M140 (a and b)
-2-(3-cyanopyridyl)
N
CH
-sec-butyl


M141 (a and b)
-2-(3-bromopyridyl)
N
CH
-sec-butyl


M142 (a and b)
-2-(3-iodopyridyl)
N
CH
-sec-butyl


M143 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
-sec-butyl


M144 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
-sec-butyl


M145 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
-sec-butyl


M146 (a and b)
-2-(3-chloropyrazinyl)
N
CH
-sec-butyl


M147 (a and b)
-2-(3-methylpyrazinyl)
N
CH
-sec-butyl


M148 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
-sec-butyl


M149 (a and b)
-3-(4-chloropyridazinyl)
N
CH
-sec-butyl


M150 (a and b)
-3-(4-methylpyridazinyl)
N
CH
-sec-butyl


M151 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
-sec-butyl


M152 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
-sec-butyl


M153 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-sec-butyl


M154 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
-sec-butyl


M155 (a and b)
-2-(3-chloropyridyl)
CH
N
-sec-butyl


M156 (a and b)
-2-(3-fluoropyridyl)
CH
N
-sec-butyl


M157 (a and b)
-2-(3-methylpyridyl)
CH
N
-sec-butyl


M158 (a and b)
-2-(3-CF3-pyridyl)
CH
N
-sec-butyl


M159 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
-sec-butyl


M160 (a and b)
-2-(3-hydroxypyridyl)
CH
N
-sec-butyl


M161 (a and b)
-2-(3-nitropyridyl)
CH
N
-sec-butyl


M162 (a and b)
-2-(3-cyanopyridyl)
CH
N
-sec-butyl


M163 (a and b)
-2-(3-bromopyridyl)
CH
N
-sec-butyl


M164 (a and b)
-2-(3-iodopyridyl)
CH
N
-sec-butyl


M165 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
-sec-butyl


M166 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
-sec-butyl


M167 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
-sec-butyl


M168 (a and b)
-2-(3-chloropyrazinyl)
CH
N
-sec-butyl


M169 (a and b)
-2-(3-methylpyrazinyl)
CH
N
-sec-butyl


M170 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
-sec-butyl


M171 (a and b)
-3-(4-chloropyridazinyl)
CH
N
-sec-butyl


M172 (a and b)
-3-(4-methylpyridazinyl)
CH
N
-sec-butyl


M173 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
-sec-butyl


M174 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
-sec-butyl


M175 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-sec-butyl


M176 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
-sec-butyl


M177 (a and b)
-2-(3-chloropyridyl)
N
CH
-iso-propyl


M178 (a and b)
-2-(3-fluoropyridyl)
N
CH
-iso-propyl


M179 (a and b)
-2-(3-methylpyridyl)
N
CH
-iso-propyl


M180 (a and b)
-2-(3-CF3-pyridyl)
N
CH
-iso-propyl


M181 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
-iso-propyl


M182 (a and b)
-2-(3-hydroxypyridyl)
N
CH
-iso-propyl


M183 (a and b)
-2-(3-nitropyridyl)
N
CH
-iso-propyl


M184 (a and b)
-2-(3-cyanopyridyl)
N
CH
-iso-propyl


M185 (a and b)
-2-(3-bromopyridyl)
N
CH
-iso-propyl


M186 (a and b)
-2-(3-iodopyridyl)
N
CH
-iso-propyl


M187 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
-iso-propyl


M188 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
-iso-propyl


M189 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
-iso-propyl


M190 (a and b)
-2-(3-chloropyrazinyl)
N
CH
-iso-propyl


M191 (a and b)
-2-(3-methylpyrazinyl)
N
CH
-iso-propyl


M192 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
-iso-propyl


M193 (a and b)
-3-(4-chloropyridazinyl)
N
CH
-iso-propyl


M194 (a and b)
-3-(4-methylpyridazinyl)
N
CH
-iso-propyl


M195 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
-iso-propyl


M196 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
-iso-propyl


M197 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-iso-propyl


M198 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
-iso-propyl


M199 (a and b)
-2-(3-chloropyridyl)
CH
N
-iso-propyl


M200 (a and b)
-2-(3-fluoropyridyl)
CH
N
-iso-propyl


M201 (a and b)
-2-(3-methylpyridyl)
CH
N
-iso-propyl


M202 (a and b)
-2-(3-CF3-pyridyl)
CH
N
-iso-propyl


M203 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
-iso-propyl


M204 (a and b)
-2-(3-hydroxypyridyl)
CH
N
-iso-propyl


M205 (a and b)
-2-(3-nitropyridyl)
CH
N
-iso-propyl


M206 (a and b)
-2-(3-cyanopyridyl)
CH
N
-iso-propyl


M207 (a and b)
-2-(3-bromopyridyl)
CH
N
-iso-propyl


M208 (a and b)
-2-(3-iodopyridyl)
CH
N
-iso-propyl


M209 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
-iso-propyl


M210 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
-iso-propyl


M211 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
-iso-propyl


M212 (a and b)
-2-(3-chloropyrazinyl)
CH
N
-iso-propyl


M213 (a and b)
-2-(3-methylpyrazinyl)
CH
N
-iso-propyl


M214 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
-iso-propyl


M215 (a and b)
-3-(4-chloropyridazinyl)
CH
N
-iso-propyl


M216 (a and b)
-3-(4-methylpyridazinyl)
CH
N
-iso-propyl


M217 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
-iso-propyl


M218 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
-iso-propyl


M219 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-iso-propyl


M220 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
-iso-propyl


M221 (a and b)
-2-(3-chloropyridyl)
N
CH
-cyclohexyl


M222 (a and b)
-2-(3-fluoropyridyl)
N
CH
-cyclohexyl


M223 (a and b)
-2-(3-methylpyridyl)
N
CH
-cyclohexyl


M224 (a and b)
-2-(3-CF3-pyridyl)
N
CH
-cyclohexyl


M225 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
-cyclohexyl


M226 (a and b)
-2-(3-hydroxypyridyl)
N
CH
-cyclohexyl


M227 (a and b)
-2-(3-nitropyridyl)
N
CH
-cyclohexyl


M228 (a and b)
-2-(3-cyanopyridyl)
N
CH
-cyclohexyl


M229 (a and b)
-2-(3-bromopyridyl)
N
CH
-cyclohexyl


M230 (a and b)
-2-(3-iodopyridyl)
N
CH
-cyclohexyl


M231 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
-cyclohexyl


M232 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
-cyclohexyl


M233 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
-cyclohexyl


M234 (a and b)
-2-(3-chloropyrazinyl)
N
CH
-cyclohexyl


M235 (a and b)
-2-(3-methylpyrazinyl)
N
CH
-cyclohexyl


M236 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
-cyclohexyl


M237 (a and b)
-3-(4-chloropyridazinyl)
N
CH
-cyclohexyl


M238 (a and b)
-3-(4-methylpyridazinyl)
N
CH
-cyclohexyl


M239 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
-cyclohexyl


M240 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
-cyclohexyl


M241 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-cyclohexyl


M242 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
-cyclohexyl


M243 (a and b)
-2-(3-chloropyridyl)
CH
N
-cyclohexyl


M244 (a and b)
-2-(3-fluoropyridyl)
CH
N
-cyclohexyl


M245 (a and b)
-2-(3-methylpyridyl)
CH
N
-cyclohexyl


M246 (a and b)
-2-(3-CF3-pyridyl)
CH
N
-cyclohexyl


M247 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
-cyclohexyl


M248 (a and b)
-2-(3-hydroxypyridyl)
CH
N
-cyclohexyl


M249 (a and b)
-2-(3-nitropyridyl)
CH
N
-cyclohexyl


M250 (a and b)
-2-(3-cyanopyridyl)
CH
N
-cyclohexyl


M251 (a and b)
-2-(3-bromopyridyl)
CH
N
-cyclohexyl


M252 (a and b)
-2-(3-iodopyridyl)
CH
N
-cyclohexyl


M253 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
-cyclohexyl


M254 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
-cyclohexyl


M255 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
-cyclohexyl


M256 (a and b)
-2-(3-chloropyrazinyl)
CH
N
-cyclohexyl


M257 (a and b)
-2-(3-methylpyrazinyl)
CH
N
-cyclohexyl


M258 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
-cyclohexyl


M259 (a and b)
-3-(4-chloropyridazinyl)
CH
N
-cyclohexyl


M260 (a and b)
-3-(4-methylpyridazinyl)
CH
N
-cyclohexyl


M261 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
-cyclohexyl


M262 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
-cyclohexyl


M263 (a and b)
-5-(4-methylthiadiazolyl)
N
N
-cyclohexyl


M264 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
-cyclohexyl


M265 (a and b)
-2-(3-chloropyridyl)
N
CH
—CH2CF3


M266 (a and b)
-2-(3-fluoropyridyl)
N
CH
—CH2CF3


M267 (a and b)
-2-(3-methylpyridyl)
N
CH
—CH2CF3


M268 (a and b)
-2-(3-CF3-pyridyl)
N
CH
—CH2CF3


M269 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
—CH2CF3


M270 (a and b)
-2-(3-hydroxypyridyl)
N
CH
—CH2CF3


M271 (a and b)
-2-(3-nitropyridyl)
N
CH
—CH2CF3


M272 (a and b)
-2-(3-cyanopyridyl)
N
CH
—CH2CF3


M273 (a and b)
-2-(3-bromopyridyl)
N
CH
—CH2CF3


M274 (a and b)
-2-(3-iodopyridyl)
N
CH
—CH2CF3


M275 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
—CH2CF3


M276 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
—CH2CF3


M277 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
—CH2CF3


M278 (a and b)
-2-(3-chloropyrazinyl)
N
CH
—CH2CF3


M279 (a and b)
-2-(3-methylpyrazinyl)
N
CH
—CH2CF3


M280 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
—CH2CF3


M281 (a and b)
-3-(4-chloropyridazinyl)
N
CH
—CH2CF3


M282 (a and b)
-3-(4-methylpyridazinyl)
N
CH
—CH2CF3


M283 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
—CH2CF3


M284 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
—CH2CF3


M285 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—CH2CF3


M286 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
—CH2CF3


M287 (a and b)
-2-(3-chloropyridyl)
CH
N
—CH2CF3


M288 (a and b)
-2-(3-fluoropyridyl)
CH
N
—CH2CF3


M289 (a and b)
-2-(3-methylpyridyl)
CH
N
—CH2CF3


M290 (a and b)
-2-(3-CF3-pyridyl)
CH
N
—CH2CF3


M291 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
—CH2CF3


M292 (a and b)
-2-(3-hydroxypyridyl)
CH
N
—CH2CF3


M293 (a and b)
-2-(3-nitropyridyl)
CH
N
—CH2CF3


M294 (a and b)
-2-(3-cyanopyridyl)
CH
N
—CH2CF3


M295 (a and b)
-2-(3-bromopyridyl)
CH
N
—CH2CF3


M296 (a and b)
-2-(3-iodopyridyl)
CH
N
—CH2CF3


M297 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
—CH2CF3


M298 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
—CH2CF3


M299 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
—CH2CF3


M300 (a and b)
-2-(3-chloropyrazinyl)
CH
N
—CH2CF3


M301 (a and b)
-2-(3-methylpyrazinyl)
CH
N
—CH2CF3


M302 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
—CH2CF3


M303 (a and b)
-3-(4-chloropyridazinyl)
CH
N
—CH2CF3


M304 (a and b)
-3-(4-methylpyridazinyl)
CH
N
—CH2CF3


M305 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
—CH2CF3


M306 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
—CH2CF3


M307 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—CH2CF3


M308 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
—CH2CF3


M309 (a and b)
-2-(3-chloropyridyl)
N
CH
—OCF3


M310 (a and b)
-2-(3-fluoropyridyl)
N
CH
—OCF3


M311 (a and b)
-2-(3-methylpyridyl)
N
CH
—OCF3


M312 (a and b)
-2-(3-CF3-pyridyl)
N
CH
—OCF3


M313 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
—OCF3


M314 (a and b)
-2-(3-hydroxypyridyl)
N
CH
—OCF3


M315 (a and b)
-2-(3-nitropyridyl)
N
CH
—OCF3


M316 (a and b)
-2-(3-cyanopyridyl)
N
CH
—OCF3


M317 (a and b)
-2-(3-bromopyridyl)
N
CH
—OCF3


M318 (a and b)
-2-(3-iodopyridyl)
N
CH
—OCF3


M319 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
—OCF3


M320 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
—OCF3


M321 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
—OCF3


M322 (a and b)
-2-(3-chloropyrazinyl)
N
CH
—OCF3


M323 (a and b)
-2-(3-methylpyrazinyl)
N
CH
—OCF3


M324 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
—OCF3


M325 (a and b)
-3-(4-chloropyridazinyl)
N
CH
—OCF3


M326 (a and b)
-3-(4-methylpyridazinyl)
N
CH
—OCF3


M327 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
—OCF3


M328 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
—OCF3


M329 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—OCF3


M330 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
—OCF3


M331 (a and b)
-2-(3-chloropyridyl)
CH
N
—OCF3


M332 (a and b)
-2-(3-fluoropyridyl)
CH
N
—OCF3


M333 (a and b)
-2-(3-methylpyridyl)
CH
N
—OCF3


M334 (a and b)
-2-(3-CF3-pyridyl)
CH
N
—OCF3


M335 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
—OCF3


M336 (a and b)
-2-(3-hydroxypyridyl)
CH
N
—OCF3


M337 (a and b)
-2-(3-nitropyridyl)
CH
N
—OCF3


M338 (a and b)
-2-(3-cyanopyridyl)
CH
N
—OCF3


M339 (a and b)
-2-(3-bromopyridyl)
CH
N
—OCF3


M340 (a and b)
-2-(3-iodopyridyl)
CH
N
—OCF3


M341 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
—OCF3


M342 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
—OCF3


M343 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
—OCF3


M344 (a and b)
-2-(3-chloropyrazinyl)
CH
N
—OCF3


M345 (a and b)
-2-(3-methylpyrazinyl)
CH
N
—OCF3


M346 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
—OCF3


M347 (a and b)
-3-(4-chloropyridazinyl)
CH
N
—OCF3


M348 (a and b)
-3-(4-methylpyridazinyl)
CH
N
—OCF3


M349 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
—OCF3


M350 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
—OCF3


M351 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—OCF3


M352 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
—OCF3


M353 (a and b)
-2-(3-chloropyridyl)
N
CH
—SCF3


M354 (a and b)
-2-(3-fluoropyridyl)
N
CH
—SCF3


M355 (a and b)
-2-(3-methylpyridyl)
N
CH
—SCF3


M356 (a and b)
-2-(3-CF3-pyridyl)
N
CH
—SCF3


M357 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
—SCF3


M358 (a and b)
-2-(3-hydroxypyridyl)
N
CH
—SCF3


M359 (a and b)
-2-(3-nitropyridyl)
N
CH
—SCF3


M360 (a and b)
-2-(3-cyanopyridyl)
N
CH
—SCF3


M361 (a and b)
-2-(3-bromopyridyl)
N
CH
—SCF3


M362 (a and b)
-2-(3-iodopyridyl)
N
CH
—SCF3


M363 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
—SCF3


M364 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
—SCF3


M365 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
—SCF3


M366 (a and b)
-2-(3-chloropyrazinyl)
N
CH
—SCF3


M367 (a and b)
-2-(3-methylpyrazinyl)
N
CH
—SCF3


M368 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
—SCF3


M369 (a and b)
-3-(4-chloropyridazinyl)
N
CH
—SCF3


M370 (a and b)
-3-(4-methylpyridazinyl)
N
CH
—SCF3


M371 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
—SCF3


M372 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
—SCF3


M373 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—SCF3


M374 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
—SCF3


M375 (a and b)
-2-(3-chloropyridyl)
CH
N
—SCF3


M376 (a and b)
-2-(3-fluoropyridyl)
CH
N
—SCF3


M377 (a and b)
-2-(3-methylpyridyl)
CH
N
—SCF3


M378 (a and b)
-2-(3-CF3-pyridyl)
CH
N
—SCF3


M379 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
—SCF3


M380 (a and b)
-2-(3-hydroxypyridyl)
CH
N
—SCF3


M381 (a and b)
-2-(3-nitropyridyl)
CH
N
—SCF3


M382 (a and b)
-2-(3-cyanopyridyl)
CH
N
—SCF3


M383 (a and b)
-2-(3-bromopyridyl)
CH
N
—SCF3


M384 (a and b)
-2-(3-iodopyridyl)
CH
N
—SCF3


M385 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
—SCF3


M386 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
—SCF3


M387 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
—SCF3


M388 (a and b)
-2-(3-chloropyrazinyl)
CH
N
—SCF3


M389 (a and b)
-2-(3-methylpyrazinyl)
CH
N
—SCF3


M390 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
—SCF3


M391 (a and b)
-3-(4-chloropyridazinyl)
CH
N
—SCF3


M392 (a and b)
-3-(4-methylpyridazinyl)
CH
N
—SCF3


M393 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
—SCF3


M394 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
—SCF3


M395 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—SCF3


M396 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
—SCF3


M397 (a and b)
-2-(3-chloropyridyl)
N
CH
—H


M398 (a and b)
-2-(3-fluoropyridyl)
N
CH
—H


M399 (a and b)
-2-(3-methylpyridyl)
N
CH
—H


M400 (a and b)
-2-(3-CF3-pyridyl)
N
CH
—H


M401 (a and b)
-2-(3-CHF2-pyridyl)
N
CH
—H


M402 (a and b)
-2-(3-hydroxypyridyl)
N
CH
—H


M403 (a and b)
-2-(3-nitropyridyl)
N
CH
—H


M404 (a and b)
-2-(3-cyanopyridyl)
N
CH
—H


M405 (a and b)
-2-(3-bromopyridyl)
N
CH
—H


M406 (a and b)
-2-(3-iodopyridyl)
N
CH
—H


M407 (a and b)
-4-(5-chloropyrimidinyl)
N
CH
—H


M408 (a and b)
-4-(5-methylpyrimidinyl)
N
CH
—H


M409 (a and b)
-4-(5-fluoropyrimidinyl)
N
CH
—H


M410 (a and b)
-2-(3-chloropyrazinyl)
N
CH
—H


M411 (a and b)
-2-(3-methylpyrazinyl)
N
CH
—H


M412 (a and b)
-2-(3-fluoropyrazinyl)
N
CH
—H


M413 (a and b)
-3-(4-chloropyridazinyl)
N
CH
—H


M414 (a and b)
-3-(4-methylpyridazinyl)
N
CH
—H


M415 (a and b)
-3-(4-fluoropyridazinyl)
N
CH
—H


M416 (a and b)
-5-(4-chlorothiadiazolyl)
N
CH
—H


M417 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—H


M418 (a and b)
-5-(4-fluorothiadiazolyl)
N
CH
—H


M419 (a and b)
-2-(3-chloropyridyl)
CH
N
—H


M420 (a and b)
-2-(3-fluoropyridyl)
CH
N
—H


M421 (a and b)
-2-(3-methylpyridyl)
CH
N
—H


M422 (a and b)
-2-(3-CF3-pyridyl)
CH
N
—H


M423 (a and b)
-2-(3-CHF2-pyridyl)
CH
N
—H


M424 (a and b)
-2-(3-hydroxypyridyl)
CH
N
—H


M425 (a and b)
-2-(3-nitropyridyl)
CH
N
—H


M426 (a and b)
-2-(3-cyanopyridyl)
CH
N
—H


M427 (a and b)
-2-(3-bromopyridyl)
CH
N
—H


M428 (a and b)
-2-(3-iodopyridyl)
CH
N
—H


M429 (a and b)
-4-(5-chloropyrimidinyl)
CH
N
—H


M430 (a and b)
-4-(5-methylpyrimidinyl)
CH
N
—H


M431 (a and b)
-4-(5-fluoropyrimidinyl)
CH
N
—H


M432 (a and b)
-2-(3-chloropyrazinyl)
CH
N
—H


M433 (a and b)
-2-(3-methylpyrazinyl)
CH
N
—H


M434 (a and b)
-2-(3-fluoropyrazinyl)
CH
N
—H


M435 (a and b)
-3-(4-chloropyridazinyl)
CH
N
—H


M436 (a and b)
-3-(4-methylpyridazinyl)
CH
N
—H


M437 (a and b)
-3-(4-fluoropyridazinyl)
CH
N
—H


M438 (a and b)
-5-(4-chlorothiadiazolyl)
CH
N
—H


M439 (a and b)
-5-(4-methylthiadiazolyl)
N
N
—H


M440 (a and b)
-5-(4-fluorothiadiazolyl)
CH
N
—H





(a) means that R3 is —H.


(b) means that R3 is —CH3.













TABLE 14







(In)




embedded image







and pharmaceutically acceptable salts thereof, wherein:









Compound
R1
R8a





N1 (a and b)
—H
—H


N2 (a and b)
—H
-tert-butyl


N3 (a and b)
—H
-iso-butyl


N4 (a and b)
—H
-sec-butyl


N5 (a and b)
—H
-iso-propyl


N6 (a and b)
—H
-n-propyl


N7 (a and b)
—H
-cyclohexyl


N8 (a and b)
—H
-tert-butoxy


N9 (a and b)
—H
-isopropoxy


N10 (a and b)
—H
—CF3


N11 (a and b)
—H
—CH2CF3


N12 (a and b)
—H
—OCF3


N13 (a and b)
—H
—Cl


N14 (a and b)
—H
—Br


N15 (a and b)
—H
—I


N16 (a and b)
—H
-n-butyl


N17 (a and b)
—H
—CH3


N18 (a and b)
—H
—SCF3


N19 (a and b)
—H
—N(CH2CH3)2


N20 (a and b)
—H
—OCF2CHF2


N21 (a and b)
—H
—C(OH)(CF3)2


N22 (a and b)
—H
-(1,1-dimethyl-pentyl)


N23 (a and b)
—H
-(1,1-dimethyl-acetic




acid) ethyl ester


N24 (a and b)
—H
—N-piperidinyl


N25 (a and b)
—Cl
—H


N26 (a and b)
—Cl
-tert-butyl


N27 (a and b)
—Cl
-iso-butyl


N28 (a and b)
—Cl
-sec-butyl


N29 (a and b)
—Cl
-iso-propyl


N30 (a and b)
—Cl
-n-propyl


N31 (a and b)
—Cl
-cyclohexyl


N32 (a and b)
—Cl
-tert-butoxy


N33 (a and b)
—Cl
-isopropoxy


N34 (a and b)
—Cl
—CF3


N35 (a and b)
—Cl
—CH2CF3


N36 (a and b)
—Cl
—OCF3


N37 (a and b)
—Cl
—Cl


N38 (a and b)
—Cl
—Br


N39 (a and b)
—Cl
—I


N40 (a and b)
—Cl
-n-butyl


N41 (a and b)
—Cl
—CH3


N42 (a and b)
—Cl
—SCF3


N43 (a and b)
—Cl
—N(CH2CH3)2


N44 (a and b)
—Cl
—OCF2CHF2


N45 (a and b)
—Cl
—C(OH)(CF3)2


N46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)


N47 (a and b)
—Cl
-(1,1-dimethyl-acetic




acid) ethyl ester


N48 (a and b)
—Cl
—N-piperidinyl


N49 (a and b)
—F
—H


N50 (a and b)
—F
-tert-butyl


N51 (a and b)
—F
-iso-butyl


N52 (a and b)
—F
-sec-butyl


N53 (a and b)
—F
-iso-propyl


N54 (a and b)
—F
-n-propyl


N55 (a and b)
—F
-cyclohexyl


N56 (a and b)
—F
-tert-butoxy


N57 (a and b)
—F
-isopropoxy


N58 (a and b)
—F
—CF3


N59 (a and b)
—F
—CH2CF3


N60 (a and b)
—F
—OCF3


N61 (a and b)
—F
—Cl


N62 (a and b)
—F
—Br


N63 (a and b)
—F
—I


N64 (a and b)
—F
-n-butyl


N65 (a and b)
—F
—CH3


N66 (a and b)
—F
—SCF3


N67 (a and b)
—F
—N(CH2CH3)2


N68 (a and b)
—F
—OCF2CHF2


N69 (a and b)
—F
—C(OH)(CF3)2


N70 (a and b)
—F
-(1,1-dimethyl-pentyl)


N71 (a and b)
—F
-(1,1-dimethyl-acetic




acid) ethyl ester


N72 (a and b)
—F
—N-piperidinyl


N73 (a and b)
—CH3
—H


N74 (a and b)
—CH3
-iso-butyl


N75 (a and b)
—CH3
-tert-butyl


N76 (a and b)
—CH3
-sec-butyl


N77 (a and b)
—CH3
-iso-propyl


N78 (a and b)
—CH3
-n-propyl


N79 (a and b)
—CH3
-cyclohexyl


N80 (a and b)
—CH3
-tert-butoxy


N81 (a and b)
—CH3
-isopropoxy


N82 (a and b)
—CH3
—CF3


N83 (a and b)
—CH3
—CH2CF3


N84 (a and b)
—CH3
—OCF3


N85 (a and b)
—CH3
—Cl


N86 (a and b)
—CH3
—Br


N87 (a and b)
—CH3
—I


N88 (a and b)
—CH3
-n-butyl


N89 (a and b)
—CH3
—CH3


N90 (a and b)
—CH3
—SCF3


N91 (a and b)
—CH3
—N(CH2CH3)2


N92 (a and b)
—CH3
—OCF2CHF2


N93 (a and b)
—CH3
—C(OH)(CF3)2


N94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)


N95 (a and b)
—CH3
-(1,1-dimethyl-acetic




acid) ethyl ester


N96 (a and b)
—CH3
—N-piperidinyl


N97 (a and b)
—CF3
—H


N98 (a and b)
—CF3
-tert-butyl


N99 (a and b)
—CF3
-iso-butyl


N100 (a and b)
—CF3
-sec-butyl


N101 (a and b)
—CF3
-iso-propyl


N102 (a and b)
—CF3
-n-propyl


N103 (a and b)
—CF3
-cyclohexyl


N104 (a and b)
—CF3
-tert-butoxy


N105 (a and b)
—CF3
-isopropoxy


N106 (a and b)
—CF3
—CF3


N107 (a and b)
—CF3
—CH2CF3


N108 (a and b)
—CF3
—OCF3


N109 (a and b)
—CF3
—Cl


N110 (a and b)
—CF3
—Br


N111 (a and b)
—CF3
—I


N112 (a and b)
—CF3
-n-butyl


N113 (a and b)
—CF3
—CH3


N114 (a and b)
—CF3
—SCF3


N115 (a and b)
—CF3
—N(CH2CH3)2


N116 (a and b)
—CF3
—OCF2CHF2


N117 (a and b)
—CF3
—C(OH)(CF3)2


N118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)


N119 (a and b)
—CF3
-(1,1-dimethyl-acetic




acid) ethyl ester


N120 (a and b)
—CF3
—N-piperidinyl


N121 (a and b)
—CHF2
-tert-butyl


N122 (a and b)
—CHF2
—H


N123 (a and b)
—CHF2
-iso-butyl


N124 (a and b)
—CHF2
-sec-butyl


N125 (a and b)
—CHF2
-iso-propyl


N126 (a and b)
—CHF2
-n-propyl


N127 (a and b)
—CHF2
-cyclohexyl


N128 (a and b)
—CHF2
-tert-butoxy


N129 (a and b)
—CHF2
-isopropoxy


N130 (a and b)
—CHF2
—CF3


N131 (a and b)
—CHF2
—CH2CF3


N132 (a and b)
—CHF2
—OCF3


N133 (a and b)
—CHF2
—Cl


N134 (a and b)
—CHF2
—Br


N135 (a and b)
—CHF2
—I


N136 (a and b)
—CHF2
-n-butyl


N137 (a and b)
—CHF2
—CH3


N138 (a and b)
—CHF2
—SCF3


N139 (a and b)
—CHF2
—N(CH2CH3)2


N140 (a and b)
—CHF2
—OCF2CHF2


N141 (a and b)
—CHF2
—C(OH)(CF3)2


N142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)


N143 (a and b)
—CHF2
-(1,1-dimethyl-acetic




acid) ethyl ester


N144 (a and b)
—CHF2
—N-piperidinyl


N145 (a and b)
—OH
—H


N146 (a and b)
—OH
-tert-butyl


N147 (a and b)
—OH
-iso-butyl


N148 (a and b)
—OH
-sec-butyl


N149 (a and b)
—OH
-iso-propyl


N150 (a and b)
—OH
-n-propyl


N151 (a and b)
—OH
-cyclohexyl


N152 (a and b)
—OH
-tert-butoxy


N153 (a and b)
—OH
-isopropoxy


N154 (a and b)
—OH
—CF3


N155 (a and b)
—OH
—CH2CF3


N156 (a and b)
—OH
—OCF3


N157 (a and b)
—OH
—Cl


N158 (a and b)
—OH
—Br


N159 (a and b)
—OH
—I


N160 (a and b)
—OH
-n-butyl


N161 (a and b)
—OH
—CH3


N162 (a and b)
—OH
—SCF3


N163 (a and b)
—OH
—N(CH2CH3)2


N164 (a and b)
—OH
—OCF2CHF2


N165 (a and b)
—OH
—C(OH)(CF3)2


N166 (a and b)
—OH
-(1,1-dimethyl-pentyl)


N167 (a and b)
—OH
-(1,1-dimethyl-acetic




acid) ethyl ester


N168 (a and b)
—OH
—N-piperidinyl


N169 (a and b)
—NO2
—H


N170 (a and b)
—NO2
-tert-butyl


N171 (a and b)
—NO2
-iso-butyl


N172 (a and b)
—NO2
-sec-butyl


N173 (a and b)
—NO2
-iso-propyl


N174 (a and b)
—NO2
-n-propyl


N175 (a and b)
—NO2
-cyclohexyl


N176 (a and b)
—NO2
-tert-butoxy


N177 (a and b)
—NO2
-isopropoxy


N178 (a and b)
—NO2
—CF3


N179 (a and b)
—NO2
—CH2CF3


N180 (a and b)
—NO2
—OCF3


N181 (a and b)
—NO2
—Cl


N182 (a and b)
—NO2
—Br


N183 (a and b)
—NO2
—I


N184 (a and b)
—NO2
-n-butyl


N185 (a and b)
—NO2
—CH3


N186 (a and b)
—NO2
—SCF3


N187 (a and b)
—NO2
—N(CH2CH3)2


N188 (a and b)
—NO2
—OCF2CHF2


N189 (a and b)
—NO2
—C(OH)(CF3)2


N190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)


N191 (a and b)
—NO2
-(1,1-dimethyl-acetic




acid) ethyl ester


N192 (a and b)
—NO2
—N-piperidinyl


N193 (a and b)
—CN
—H


N194 (a and b)
—CN
-tert-butyl


N195 (a and b)
—CN
-iso-butyl


N196 (a and b)
—CN
-sec-butyl


N197 (a and b)
—CN
-iso-propyl


N198 (a and b)
—CN
-n-propyl


N199 (a and b)
—CN
-cyclohexyl


N200 (a and b)
—CN
-tert-butoxy


N201 (a and b)
—CN
-isopropoxy


N202 (a and b)
—CN
—CF3


N203 (a and b)
—CN
—CH2CF3


N204 (a and b)
—CN
—OCF3


N205 (a and b)
—CN
—Cl


N206 (a and b)
—CN
—Br


N207 (a and b)
—CN
—I


N208 (a and b)
—CN
-n-butyl


N209 (a and b)
—CN
—CH3


N210 (a and b)
—CN
—SCF3


N211 (a and b)
—CN
—N(CH2CH3)2


N212 (a and b)
—CN
—OCF2CHF2


N213 (a and b)
—CN
—C(OH)(CF3)2


N214 (a and b)
—CN
-(1,1-dimethyl-pentyl)


N215 (a and b)
—CN
-(1,1-dimethyl-acetic




acid) ethyl ester


N216 (a and b)
—CN
—N-piperidinyl


N217 (a and b)
—Br
—H


N218 (a and b)
—Br
-tert-butyl


N219 (a and b)
—Br
-iso-butyl


N220 (a and b)
—Br
-sec-butyl


N221 (a and b)
—Br
-iso-propyl


N222 (a and b)
—Br
-n-propyl


N223 (a and b)
—Br
-cyclohexyl


N224 (a and b)
—Br
-tert-butoxy


N225 (a and b)
—Br
-isopropoxy


N226 (a and b)
—Br
—CF3


N227 (a and b)
—Br
—CH2CF3


N228 (a and b)
—Br
—OCF3


N229 (a and b)
—Br
—Cl


N230 (a and b)
—Br
—Br


N231 (a and b)
—Br
—I


N232 (a and b)
—Br
-n-butyl


N233 (a and b)
—Br
—CH3


N234 (a and b)
—Br
—SCF3


N235 (a and b)
—Br
—N(CH2CH3)2


N236 (a and b)
—Br
—OCF2CHF2


N237 (a and b)
—Br
—C(OH)(CF3)2


N238 (a and b)
—Br
-(1,1-dimethyl-pentyl)


N239 (a and b)
—Br
-(1,1-dimethyl-acetic




acid) ethyl ester


N240 (a and b)
—Br
—N-piperidinyl


N241 (a and b)
—I
-tert-butyl


N242 (a and b)
—I
—H


N243 (a and b)
—I
-iso-butyl


N244 (a and b)
—I
-sec-butyl


N245 (a and b)
—I
-iso-propyl


N246 (a and b)
—I
-n-propyl


N247 (a and b)
—I
-cyclohexyl


N248 (a and b)
—I
-tert-butoxy


N249 (a and b)
—I
-isopropoxy


N250 (a and b)
—I
—CF3


N251 (a and b)
—I
—CH2CF3


N252 (a and b)
—I
—OCF3


N253 (a and b)
—I
—Cl


N254 (a and b)
—I
—Br


N255 (a and b)
—I
—I


N256 (a and b)
—I
-n-butyl


N257 (a and b)
—I
—CH3


N258 (a and b)
—I
—SCF3


N259 (a and b)
—I
—N(CH2CH3)2


N260 (a and b)
—I
—OCF2CHF2


N261 (a and b)
—I
—C(OH)(CF3)2


N262 (a and b)
—I
-(1,1-dimethyl-pentyl)


N263 (a and b)
—I
-(1,1-dimethyl-acetic




acid) ethyl ester


N264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 15








(Io)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






O1 (a and b)
—H
—H



O2 (a and b)
—H
-tert-butyl



O3 (a and b)
—H
-iso-butyl



O4 (a and b)
—H
-sec-butyl



O5 (a and b)
—H
-iso-propyl



O6 (a and b)
—H
-n-propyl



O7 (a and b)
—H
-cyclohexyl



O8 (a and b)
—H
-tert-butoxy



O9 (a and b)
—H
-isopropoxy



O10 (a and b)
—H
—CF3



O11 (a and b)
—H
—CH2CF3



O12 (a and b)
—H
—OCF3



O13 (a and b)
—H
—Cl



O14 (a and b)
—H
—Br



O15 (a and b)
—H
—I



O16 (a and b)
—H
-n-butyl



O17 (a and b)
—H
—CH3



O18 (a and b)
—H
—SCF3



O19 (a and b)
—H
—N(CH2CH3)2



O20 (a and b)
—H
—OCF2CHF2



O21 (a and b)
—H
—C(OH)(CF3)2



O22 (a and b)
—H
-(1,1-dimethyl-pentyl)



O23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



O24 (a and b)
—H
—N-piperidinyl



O25 (a and b)
—Cl
—H



O26 (a and b)
—Cl
-tert-butyl



O27 (a and b)
—Cl
-iso-butyl



O28 (a and b)
—Cl
-sec-butyl



O29 (a and b)
—Cl
-iso-propyl



O30 (a and b)
—Cl
-n-propyl



O31 (a and b)
—Cl
-cyclohexyl



O32 (a and b)
—Cl
-tert-butoxy



O33 (a and b)
—Cl
-isopropoxy



O34 (a and b)
—Cl
—CF3



O35 (a and b)
—Cl
—CH2CF3



O36 (a and b)
—Cl
—OCF3



O37 (a and b)
—Cl
—Cl



O38 (a and b)
—Cl
—Br



O39 (a and b)
—Cl
—I



O40 (a and b)
—Cl
-n-butyl



O41 (a and b)
—Cl
—CH3



O42 (a and b)
—Cl
—SCF3



O43 (a and b)
—Cl
—N(CH2CH3)2



O44 (a and b)
—Cl
—OCF2CHF2



O45 (a and b)
—Cl
—C(OH)(CF3)2



O46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



O47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



O48 (a and b)
—Cl
—N-piperidinyl



O49 (a and b)
—F
—H



O50 (a and b)
—F
-tert-butyl



O51 (a and b)
—F
-iso-butyl



O52 (a and b)
—F
-sec-butyl



O53 (a and b)
—F
-iso-propyl



O54 (a and b)
—F
-n-propyl



O55 (a and b)
—F
-cyclohexyl



O56 (a and b)
—F
-tert-butoxy



O57 (a and b)
—F
-isopropoxy



O58 (a and b)
—F
—CF3



O59 (a and b)
—F
—CH2CF3



O60 (a and b)
—F
—OCF3



O61 (a and b)
—F
—Cl



O62 (a and b)
—F
—Br



O63 (a and b)
—F
—I



O64 (a and b)
—F
-n-butyl



O65 (a and b)
—F
—CH3



O66 (a and b)
—F
—SCF3



O67 (a and b)
—F
—N(CH2CH3)2



O68 (a and b)
—F
—OCF2CHF2



O69 (a and b)
—F
—C(OH)(CF3)2



O70 (a and b)
—F
-(1,1-dimethyl-pentyl)



O71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



O72 (a and b)
—F
—N-piperidinyl



O73 (a and b)
—CH3
—H



O74 (a and b)
—CH3
-iso-butyl



O75 (a and b)
—CH3
-tert-butyl



O76 (a and b)
—CH3
-sec-butyl



O77 (a and b)
—CH3
-iso-propyl



O78 (a and b)
—CH3
-n-propyl



O79 (a and b)
—CH3
-cyclohexyl



O80 (a and b)
—CH3
-tert-butoxy



O81 (a and b)
—CH3
-isopropoxy



O82 (a and b)
—CH3
—CF3



O83 (a and b)
—CH3
—CH2CF3



O84 (a and b)
—CH3
—OCF3



O85 (a and b)
—CH3
—Cl



O86 (a and b)
—CH3
—Br



O87 (a and b)
—CH3
—I



O88 (a and b)
—CH3
-n-butyl



O89 (a and b)
—CH3
—CH3



O90 (a and b)
—CH3
—SCF3



O91 (a and b)
—CH3
—N(CH2CH3)2



O92 (a and b)
—CH3
—OCF2CHF2



O93 (a and b)
—CH3
—C(OH)(CF3)2



O94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



O95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



O96 (a and b)
—CH3
—N-piperidinyl



O97 (a and b)
—CF3
—H



O98 (a and b)
—CF3
-tert-butyl



O99 (a and b)
—CF3
-iso-butyl



O100 (a and b)
—CF3
-sec-butyl



O101 (a and b)
—CF3
-iso-propyl



O102 (a and b)
—CF3
-n-propyl



O103 (a and b)
—CF3
-cyclohexyl



O104 (a and b)
—CF3
-tert-butoxy



O105 (a and b)
—CF3
-isopropoxy



O106 (a and b)
—CF3
—CF3



O107 (a and b)
—CF3
—CH2CF3



O108 (a and b)
—CF3
—OCF3



O109 (a and b)
—CF3
—Cl



O110 (a and b)
—CF3
—Br



O111 (a and b)
—CF3
—I



O112 (a and b)
—CF3
-n-butyl



O113 (a and b)
—CF3
—CH3



O114 (a and b)
—CF3
—SCF3



O115 (a and b)
—CF3
—N(CH2CH3)2



O116 (a and b)
—CF3
—OCF2CHF2



O117 (a and b)
—CF3
—C(OH)(CF3)2



O118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



O119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



O120 (a and b)
—CF3
—N-piperidinyl



O121 (a and b)
—CHF2
-tert-butyl



O122 (a and b)
—CHF2
—H



O123 (a and b)
—CHF2
-iso-butyl



O124 (a and b)
—CHF2
-sec-butyl



O125 (a and b)
—CHF2
-iso-propyl



O126 (a and b)
—CHF2
-n-propyl



O127 (a and b)
—CHF2
-cyclohexyl



O128 (a and b)
—CHF2
-tert-butoxy



O129 (a and b)
—CHF2
-isopropoxy



O130 (a and b)
—CHF2
—CF3



O131 (a and b)
—CHF2
—CH2CF3



O132 (a and b)
—CHF2
—OCF3



O133 (a and b)
—CHF2
—Cl



O134 (a and b)
—CHF2
—Br



O135 (a and b)
—CHF2
—I



O136 (a and b)
—CHF2
-n-butyl



O137 (a and b)
—CHF2
—CH3



O138 (a and b)
—CHF2
—SCF3



O139 (a and b)
—CHF2
—N(CH2CH3)2



O140 (a and b)
—CHF2
—OCF2CHF2



O141 (a and b)
—CHF2
—C(OH)(CF3)2



O142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



O143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



O144 (a and b)
—CHF2
—N-piperidinyl



O145 (a and b)
—OH
—H



O146 (a and b)
—OH
-tert-butyl



O147 (a and b)
—OH
-iso-butyl



O148 (a and b)
—OH
-sec-butyl



O149 (a and b)
—OH
-iso-propyl



O150 (a and b)
—OH
-n-propyl



O151 (a and b)
—OH
-cyclohexyl



O152 (a and b)
—OH
-tert-butoxy



O153 (a and b)
—OH
-isopropoxy



O154 (a and b)
—OH
—CF3



O155 (a and b)
—OH
—CH2CF3



O156 (a and b)
—OH
—OCF3



O157 (a and b)
—OH
—Cl



O158 (a and b)
—OH
—Br



O159 (a and b)
—OH
—I



O160 (a and b)
—OH
-n-butyl



O161 (a and b)
—OH
—CH3



O162 (a and b)
—OH
—SCF3



O163 (a and b)
—OH
—N(CH2CH3)2



O164 (a and b)
—OH
—OCF2CHF2



O165 (a and b)
—OH
—C(OH)(CF3)2



O166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



O167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



O168 (a and b)
—OH
—N-piperidinyl



O169 (a and b)
—NO2
—H



O170 (a and b)
—NO2
-tert-butyl



O171 (a and b)
—NO2
-iso-butyl



O172 (a and b)
—NO2
-sec-butyl



O173 (a and b)
—NO2
-iso-propyl



O174 (a and b)
—NO2
-n-propyl



O175 (a and b)
—NO2
-cyclohexyl



O176 (a and b)
—NO2
-tert-butoxy



O177 (a and b)
—NO2
-isopropoxy



O178 (a and b)
—NO2
—CF3



O179 (a and b)
—NO2
—CH2CF3



O180 (a and b)
—NO2
—OCF3



O181 (a and b)
—NO2
—Cl



O182 (a and b)
—NO2
—Br



O183 (a and b)
—NO2
—I



O184 (a and b)
—NO2
-n-butyl



O185 (a and b)
—NO2
—CH3



O186 (a and b)
—NO2
—SCF3



O187 (a and b)
—NO2
—N(CH2CH3)2



O188 (a and b)
—NO2
—OCF2CHF2



O189 (a and b)
—NO2
—C(OH)(CF3)2



O190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



O191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



O192 (a and b)
—NO2
—N-piperidinyl



O193 (a and b)
—CN
—H



O194 (a and b)
—CN
-tert-butyl



O195 (a and b)
—CN
-iso-butyl



O196 (a and b)
—CN
-sec-butyl



O197 (a and b)
—CN
-iso-propyl



O198 (a and b)
—CN
-n-propyl



O199 (a and b)
—CN
-cyclohexyl



O200 (a and b)
—CN
-tert-butoxy



O201 (a and b)
—CN
-isopropoxy



O202 (a and b)
—CN
—CF3



O203 (a and b)
—CN
—CH2CF3



O204 (a and b)
—CN
—OCF3



O205 (a and b)
—CN
—Cl



O206 (a and b)
—CN
—Br



O207 (a and b)
—CN
—I



O208 (a and b)
—CN
-n-butyl



O209 (a and b)
—CN
—CH3



O210 (a and b)
—CN
—SCF3



O211 (a and b)
—CN
—N(CH2CH3)2



O212 (a and b)
—CN
—OCF2CHF2



O213 (a and b)
—CN
—C(OH)(CF3)2



O214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



O215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



O216 (a and b)
—CN
—N-piperidinyl



O217 (a and b)
—Br
—H



O218 (a and b)
—Br
-tert-butyl



O219 (a and b)
—Br
-iso-butyl



O220 (a and b)
—Br
-sec-butyl



O221 (a and b)
—Br
-iso-propyl



O222 (a and b)
—Br
-n-propyl



O223 (a and b)
—Br
-cyclohexyl



O224 (a and b)
—Br
-tert-butoxy



O225 (a and b)
—Br
-isopropoxy



O226 (a and b)
—Br
—CF3



O227 (a and b)
—Br
—CH2CF3



O228 (a and b)
—Br
—OCF3



O229 (a and b)
—Br
—Cl



O230 (a and b)
—Br
—Br



O231 (a and b)
—Br
—I



O232 (a and b)
—Br
-n-butyl



O233 (a and b)
—Br
—CH3



O234 (a and b)
—Br
—SCF3



O235 (a and b)
—Br
—N(CH2CH3)2



O236 (a and b)
—Br
—OCF2CHF2



O237 (a and b)
—Br
—C(OH)(CF3)2



O238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



O239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



O240 (a and b)
—Br
—N-piperidinyl



O241 (a and b)
—I
-tert-butyl



O242 (a and b)
—I
—H



O243 (a and b)
—I
-iso-butyl



O244 (a and b)
—I
-sec-butyl



O245 (a and b)
—I
-iso-propyl



O246 (a and b)
—I
-n-propyl



O247 (a and b)
—I
-cyclohexyl



O248 (a and b)
—I
-tert-butoxy



O249 (a and b)
—I
-isopropoxy



O250 (a and b)
—I
—CF3



O251 (a and b)
—I
—CH2CF3



O252 (a and b)
—I
—OCF3



O253 (a and b)
—I
—Cl



O254 (a and b)
—I
—Br



O255 (a and b)
—I
—I



O256 (a and b)
—I
-n-butyl



O257 (a and b)
—I
—CH3



O258 (a and b)
—I
—SCF3



O259 (a and b)
—I
—N(CH2CH3)2



O260 (a and b)
—I
—OCF2CHF2



O261 (a and b)
—I
—C(OH)(CF3)2



O262 (a and b)
—I
-(1,1-dimethyl-pentyl)



O263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



O264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 16








(Ip)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






P1 (a and b)
—H
—H



P2 (a and b)
—H
-tert-butyl



P3 (a and b)
—H
-iso-butyl



P4 (a and b)
—H
-sec-butyl



P5 (a and b)
—H
-iso-propyl



P6 (a and b)
—H
-n-propyl



P7 (a and b)
—H
-cyclohexyl



P8 (a and b)
—H
-tert-butoxy



P9 (a and b)
—H
-isopropoxy



P10 (a and b)
—H
—CF3



P11 (a and b)
—H
—CH2CF3



P12 (a and b)
—H
—OCF3



P13 (a and b)
—H
—Cl



P14 (a and b)
—H
—Br



P15 (a and b)
—H
—I



P16 (a and b)
—H
-n-butyl



P17 (a and b)
—H
—CH3



P18 (a and b)
—H
—SCF3



P19 (a and b)
—H
—N(CH2CH3)2



P20 (a and b)
—H
—OCF2CHF2



P21 (a and b)
—H
—C(OH)(CF3)2



P22 (a and b)
—H
-(1,1-dimethyl-pentyl)



P23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



P24 (a and b)
—H
—N-piperidinyl



P25 (a and b)
—Cl
—H



P26 (a and b)
—Cl
-tert-butyl



P27 (a and b)
—Cl
-iso-butyl



P28 (a and b)
—Cl
-sec-butyl



P29 (a and b)
—Cl
-iso-propyl



P30 (a and b)
—Cl
-n-propyl



P31 (a and b)
—Cl
-cyclohexyl



P32 (a and b)
—Cl
-tert-butoxy



P33 (a and b)
—Cl
-isopropoxy



P34 (a and b)
—Cl
—CF3



P35 (a and b)
—Cl
—CH2CF3



P36 (a and b)
—Cl
—OCF3



P37 (a and b)
—Cl
—Cl



P38 (a and b)
—Cl
—Br



P39 (a and b)
—Cl
—I



P40 (a and b)
—Cl
-n-butyl



P41 (a and b)
—Cl
—CH3



P42 (a and b)
—Cl
—SCF3



P43 (a and b)
—Cl
—N(CH2CH3)2



P44 (a and b)
—Cl
—OCF2CHF2



P45 (a and b)
—Cl
—C(OH)(CF3)2



P46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



P47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



P48 (a and b)
—Cl
—N-piperidinyl



P49 (a and b)
—F
—H



P50 (a and b)
—F
-tert-butyl



P51 (a and b)
—F
-iso-butyl



P52 (a and b)
—F
-sec-butyl



P53 (a and b)
—F
-iso-propyl



P54 (a and b)
—F
-n-propyl



P55 (a and b)
—F
-cyclohexyl



P56 (a and b)
—F
-tert-butoxy



P57 (a and b)
—F
-isopropoxy



P58 (a and b)
—F
—CF3



P59 (a and b)
—F
—CH2CF3



P60 (a and b)
—F
—OCF3



P61 (a and b)
—F
—Cl



P62 (a and b)
—F
—Br



P63 (a and b)
—F
—I



P64 (a and b)
—F
-n-butyl



P65 (a and b)
—F
—CH3



P66 (a and b)
—F
—SCF3



P67 (a and b)
—F
—N(CH2CH3)2



P68 (a and b)
—F
—OCF2CHF2



P69 (a and b)
—F
—C(OH)(CF3)2



P70 (a and b)
—F
-(1,1-dimethyl-pentyl)



P71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



P72 (a and b)
—F
—N-piperidinyl



P73 (a and b)
—CH3
—H



P74 (a and b)
—CH3
-iso-butyl



P75 (a and b)
—CH3
-tert-butyl



P76 (a and b)
—CH3
-sec-butyl



P77 (a and b)
—CH3
-iso-propyl



P78 (a and b)
—CH3
-n-propyl



P79 (a and b)
—CH3
-cyclohexyl



P80 (a and b)
—CH3
-tert-butoxy



P81 (a and b)
—CH3
-isopropoxy



P82 (a and b)
—CH3
—CF3



P83 (a and b)
—CH3
—CH2CF3



P84 (a and b)
—CH3
—OCF3



P85 (a and b)
—CH3
—Cl



P86 (a and b)
—CH3
—Br



P87 (a and b)
—CH3
—I



P88 (a and b)
—CH3
-n-butyl



P89 (a and b)
—CH3
—CH3



P90 (a and b)
—CH3
—SCF3



P91 (a and b)
—CH3
—N(CH2CH3)2



P92 (a and b)
—CH3
—OCF2CHF2



P93 (a and b)
—CH3
—C(OH)(CF3)2



P94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



P95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



P96 (a and b)
—CH3
—N-piperidinyl



P97 (a and b)
—CF3
—H



P98 (a and b)
—CF3
-tert-butyl



P99 (a and b)
—CF3
-iso-butyl



P100 (a and b)
—CF3
-sec-butyl



P101 (a and b)
—CF3
-iso-propyl



P102 (a and b)
—CF3
-n-propyl



P103 (a and b)
—CF3
-cyclohexyl



P104 (a and b)
—CF3
-tert-butoxy



P105 (a and b)
—CF3
-isopropoxy



P106 (a and b)
—CF3
—CF3



P107 (a and b)
—CF3
—CH2CF3



P108 (a and b)
—CF3
—OCF3



P109 (a and b)
—CF3
—Cl



P110 (a and b)
—CF3
—Br



P111 (a and b)
—CF3
—I



P112 (a and b)
—CF3
-n-butyl



P113 (a and b)
—CF3
—CH3



P114 (a and b)
—CF3
—SCF3



P115 (a and b)
—CF3
—N(CH2CH3)2



P116 (a and b)
—CF3
—OCF2CHF2



P117 (a and b)
—CF3
—C(OH)(CF3)2



P118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



P119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



P120 (a and b)
—CF3
—N-piperidinyl



P121 (a and b)
—CHF2
-tert-butyl



P122 (a and b)
—CHF2
—H



P123 (a and b)
—CHF2
-iso-butyl



P124 (a and b)
—CHF2
-sec-butyl



P125 (a and b)
—CHF2
-iso-propyl



P126 (a and b)
—CHF2
-n-propyl



P127 (a and b)
—CHF2
-cyclohexyl



P128 (a and b)
—CHF2
-tert-butoxy



P129 (a and b)
—CHF2
-isopropoxy



P130 (a and b)
—CHF2
—CF3



P131 (a and b)
—CHF2
—CH2CF3



P132 (a and b)
—CHF2
—OCF3



P133 (a and b)
—CHF2
—Cl



P134 (a and b)
—CHF2
—Br



P135 (a and b)
—CHF2
—I



P136 (a and b)
—CHF2
-n-butyl



P137 (a and b)
—CHF2
—CH3



P138 (a and b)
—CHF2
—SCF3



P139 (a and b)
—CHF2
—N(CH2CH3)2



P140 (a and b)
—CHF2
—OCF2CHF2



P141 (a and b)
—CHF2
—C(OH)(CF3)2



P142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



P143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



P144 (a and b)
—CHF2
—N-piperidinyl



P145 (a and b)
—OH
—H



P146 (a and b)
—OH
-tert-butyl



P147 (a and b)
—OH
-iso-butyl



P148 (a and b)
—OH
-sec-butyl



P149 (a and b)
—OH
-iso-propyl



P150 (a and b)
—OH
-n-propyl



P151 (a and b)
—OH
-cyclohexyl



P152 (a and b)
—OH
-tert-butoxy



P153 (a and b)
—OH
-isopropoxy



P154 (a and b)
—OH
—CF3



P155 (a and b)
—OH
—CH2CF3



P156 (a and b)
—OH
—OCF3



P157 (a and b)
—OH
—Cl



P158 (a and b)
—OH
—Br



P159 (a and b)
—OH
—I



P160 (a and b)
—OH
-n-butyl



P161 (a and b)
—OH
—CH3



P162 (a and b)
—OH
—SCF3



P163 (a and b)
—OH
—N(CH2CH3)2



P164 (a and b)
—OH
—OCF2CHF2



P165 (a and b)
—OH
—C(OH)(CF3)2



P166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



P167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



P168 (a and b)
—OH
—N-piperidinyl



P169 (a and b)
—NO2
—H



P170 (a and b)
—NO2
-tert-butyl



P171 (a and b)
—NO2
-iso-butyl



P172 (a and b)
—NO2
-sec-butyl



P173 (a and b)
—NO2
-iso-propyl



P174 (a and b)
—NO2
-n-propyl



P175 (a and b)
—NO2
-cyclohexyl



P176 (a and b)
—NO2
-tert-butoxy



P177 (a and b)
—NO2
-isopropoxy



P178 (a and b)
—NO2
—CF3



P179 (a and b)
—NO2
—CH2CF3



P180 (a and b)
—NO2
—OCF3



P181 (a and b)
—NO2
—Cl



P182 (a and b)
—NO2
—Br



P183 (a and b)
—NO2
—I



P184 (a and b)
—NO2
-n-butyl



P185 (a and b)
—NO2
—CH3



P186 (a and b)
—NO2
—SCF3



P187 (a and b)
—NO2
—N(CH2CH3)2



P188 (a and b)
—NO2
—OCF2CHF2



P189 (a and b)
—NO2
—C(OH)(CF3)2



P190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



P191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



P192 (a and b)
—NO2
—N-piperidinyl



P193 (a and b)
—CN
—H



P194 (a and b)
—CN
-tert-butyl



P195 (a and b)
—CN
-iso-butyl



P196 (a and b)
—CN
-sec-butyl



P197 (a and b)
—CN
-iso-propyl



P198 (a and b)
—CN
-n-propyl



P199 (a and b)
—CN
-cyclohexyl



P200 (a and b)
—CN
-tert-butoxy



P201 (a and b)
—CN
-isopropoxy



P202 (a and b)
—CN
—CF3



P203 (a and b)
—CN
—CH2CF3



P204 (a and b)
—CN
—OCF3



P205 (a and b)
—CN
—Cl



P206 (a and b)
—CN
—Br



P207 (a and b)
—CN
—I



P208 (a and b)
—CN
-n-butyl



P209 (a and b)
—CN
—CH3



P210 (a and b)
—CN
—SCF3



P211 (a and b)
—CN
—N(CH2CH3)2



P212 (a and b)
—CN
—OCF2CHF2



P213 (a and b)
—CN
—C(OH)(CF3)2



P214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



P215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



P216 (a and b)
—CN
—N-piperidinyl



P217 (a and b)
—Br
—H



P218 (a and b)
—Br
-tert-butyl



P219 (a and b)
—Br
-iso-butyl



P220 (a and b)
—Br
-sec-butyl



P221 (a and b)
—Br
-iso-propyl



P222 (a and b)
—Br
-n-propyl



P223 (a and b)
—Br
-cyclohexyl



P224 (a and b)
—Br
-tert-butoxy



P225 (a and b)
—Br
-isopropoxy



P226 (a and b)
—Br
—CF3



P227 (a and b)
—Br
—CH2CF3



P228 (a and b)
—Br
—OCF3



P229 (a and b)
—Br
—Cl



P230 (a and b)
—Br
—Br



P231 (a and b)
—Br
—I



P232 (a and b)
—Br
-n-butyl



P233 (a and b)
—Br
—CH3



P234 (a and b)
—Br
—SCF3



P235 (a and b)
—Br
—N(CH2CH3)2



P236 (a and b)
—Br
—OCF2CHF2



P237 (a and b)
—Br
—C(OH)(CF3)2



P238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



P239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



P240 (a and b)
—Br
—N-piperidinyl



P241 (a and b)
—I
-tert-butyl



P242 (a and b)
—I
—H



P243 (a and b)
—I
-iso-butyl



P244 (a and b)
—I
-sec-butyl



P245 (a and b)
—I
-iso-propyl



P246 (a and b)
—I
-n-propyl



P247 (a and b)
—I
-cyclohexyl



P248 (a and b)
—I
-tert-butoxy



P249 (a and b)
—I
-isopropoxy



P250 (a and b)
—I
—CF3



P251 (a and b)
—I
—CH2CF3



P252 (a and b)
—I
—OCF3



P253 (a and b)
—I
—Cl



P254 (a and b)
—I
—Br



P255 (a and b)
—I
—I



P256 (a and b)
—I
-n-butyl



P257 (a and b)
—I
—CH3



P258 (a and b)
—I
—SCF3



P259 (a and b)
—I
—N(CH2CH3)2



P260 (a and b)
—I
—OCF2CHF2



P261 (a and b)
—I
—C(OH)(CF3)2



P262 (a and b)
—I
-(1,1-dimethyl-pentyl)



P263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



P264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 17








(Iq)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






Q1 (a and b)
—H
—H



Q2 (a and b)
—H
-tert-butyl



Q3 (a and b)
—H
-iso-butyl



Q4 (a and b)
—H
-sec-butyl



Q5 (a and b)
—H
-iso-propyl



Q6 (a and b)
—H
-n-propyl



Q7 (a and b)
—H
-cyclohexyl



Q8 (a and b)
—H
-tert-butoxy



Q9 (a and b)
—H
-isopropoxy



Q10 (a and b)
—H
—CF3



Q11 (a and b)
—H
—CH2CF3



Q12 (a and b)
—H
—OCF3



Q13 (a and b)
—H
—Cl



Q14 (a and b)
—H
—Br



Q15 (a and b)
—H
—I



Q16 (a and b)
—H
-n-butyl



Q17 (a and b)
—H
—CH3



Q18 (a and b)
—H
—SCF3



Q19 (a and b)
—H
—N(CH2CH3)2



Q20 (a and b)
—H
—OCF2CHF2



Q21 (a and b)
—H
—C(OH)(CF3)2



Q22 (a and b)
—H
-(1,1-dimethyl-pentyl)



Q23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



Q24 (a and b)
—H
—N-piperidinyl



Q25 (a and b)
—Cl
—H



Q26 (a and b)
—Cl
-tert-butyl



Q27 (a and b)
—Cl
-iso-butyl



Q28 (a and b)
—Cl
-sec-butyl



Q29 (a and b)
—Cl
-iso-propyl



Q30 (a and b)
—Cl
-n-propyl



Q31 (a and b)
—Cl
-cyclohexyl



Q32 (a and b)
—Cl
-tert-butoxy



Q33 (a and b)
—Cl
-isopropoxy



Q34 (a and b)
—Cl
—CF3



Q35 (a and b)
—Cl
—CH2CF3



Q36 (a and b)
—Cl
—OCF3



Q37 (a and b)
—Cl
—Cl



Q38 (a and b)
—Cl
—Br



Q39 (a and b)
—Cl
—I



Q40 (a and b)
—Cl
-n-butyl



Q41 (a and b)
—Cl
—CH3



Q42 (a and b)
—Cl
—SCF3



Q43 (a and b)
—Cl
—N(CH2CH3)2



Q44 (a and b)
—Cl
—OCF2CHF2



Q45 (a and b)
—Cl
—C(OH)(CF3)2



Q46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



Q47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



Q48 (a and b)
—Cl
—N-piperidinyl



Q49 (a and b)
—F
—H



Q50 (a and b)
—F
-tert-butyl



Q51 (a and b)
—F
-iso-butyl



Q52 (a and b)
—F
-sec-butyl



Q53 (a and b)
—F
-iso-propyl



Q54 (a and b)
—F
-n-propyl



Q55 (a and b)
—F
-cyclohexyl



Q56 (a and b)
—F
-tert-butoxy



Q57 (a and b)
—F
-isopropoxy



Q58 (a and b)
—F
—CF3



Q59 (a and b)
—F
—CH2CF3



Q60 (a and b)
—F
—OCF3



Q61 (a and b)
—F
—Cl



Q62 (a and b)
—F
—Br



Q63 (a and b)
—F
—I



Q64 (a and b)
—F
-n-butyl



Q65 (a and b)
—F
—CH3



Q66 (a and b)
—F
—SCF3



Q67 (a and b)
—F
—N(CH2CH3)2



Q68 (a and b)
—F
—OCF2CHF2



Q69 (a and b)
—F
—C(OH)(CF3)2



Q70 (a and b)
—F
-(1,1-dimethyl-pentyl)



Q71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



Q72 (a and b)
—F
—N-piperidinyl



Q73 (a and b)
—CH3
—H



Q74 (a and b)
—CH3
-iso-butyl



Q75 (a and b)
—CH3
-tert-butyl



Q76 (a and b)
—CH3
-sec-butyl



Q77 (a and b)
—CH3
-iso-propyl



Q78 (a and b)
—CH3
-n-propyl



Q79 (a and b)
—CH3
-cyclohexyl



Q80 (a and b)
—CH3
-tert-butoxy



Q81 (a and b)
—CH3
-isopropoxy



Q82 (a and b)
—CH3
—CF3



Q83 (a and b)
—CH3
—CH2CF3



Q84 (a and b)
—CH3
—OCF3



Q85 (a and b)
—CH3
—Cl



Q86 (a and b)
—CH3
—Br



Q87 (a and b)
—CH3
—I



Q88 (a and b)
—CH3
-n-butyl



Q89 (a and b)
—CH3
—CH3



Q90 (a and b)
—CH3
—SCF3



Q91 (a and b)
—CH3
—N(CH2CH3)2



Q92 (a and b)
—CH3
—OCF2CHF2



Q93 (a and b)
—CH3
—C(OH)(CF3)2



Q94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



Q95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



Q96 (a and b)
—CH3
—N-piperidinyl



Q97 (a and b)
—CF3
—H



Q98 (a and b)
—CF3
-tert-butyl



Q99 (a and b)
—CF3
-iso-butyl



Q100 (a and b)
—CF3
-sec-butyl



Q101 (a and b)
—CF3
-iso-propyl



Q102 (a and b)
—CF3
-n-propyl



Q103 (a and b)
—CF3
-cyclohexyl



Q104 (a and b)
—CF3
-tert-butoxy



Q105 (a and b)
—CF3
-isopropoxy



Q106 (a and b)
—CF3
—CF3



Q107 (a and b)
—CF3
—CH2CF3



Q108 (a and b)
—CF3
—OCF3



Q109 (a and b)
—CF3
—Cl



Q110 (a and b)
—CF3
—Br



Q111 (a and b)
—CF3
—I



Q112 (a and b)
—CF3
-n-butyl



Q113 (a and b)
—CF3
—CH3



Q114 (a and b)
—CF3
—SCF3



Q115 (a and b)
—CF3
—N(CH2CH3)2



Q116 (a and b)
—CF3
—OCF2CHF2



Q117 (a and b)
—CF3
—C(OH)(CF3)2



Q118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



Q119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



Q120 (a and b)
—CF3
—N-piperidinyl



Q121 (a and b)
—CHF2
-tert-butyl



Q122 (a and b)
—CHF2
—H



Q123 (a and b)
—CHF2
-iso-butyl



Q124 (a and b)
—CHF2
-sec-butyl



Q125 (a and b)
—CHF2
-iso-propyl



Q126 (a and b)
—CHF2
-n-propyl



Q127 (a and b)
—CHF2
-cyclohexyl



Q128 (a and b)
—CHF2
-tert-butoxy



Q129 (a and b)
—CHF2
-isopropoxy



Q130 (a and b)
—CHF2
—CF3



Q131 (a and b)
—CHF2
—CH2CF3



Q132 (a and b)
—CHF2
—OCF3



Q133 (a and b)
—CHF2
—Cl



Q134 (a and b)
—CHF2
—Br



Q135 (a and b)
—CHF2
—I



Q136 (a and b)
—CHF2
-n-butyl



Q137 (a and b)
—CHF2
—CH3



Q138 (a and b)
—CHF2
—SCF3



Q139 (a and b)
—CHF2
—N(CH2CH3)2



Q140 (a and b)
—CHF2
—OCF2CHF2



Q141 (a and b)
—CHF2
—C(OH)(CF3)2



Q142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



Q143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



Q144 (a and b)
—CHF2
—N-piperidinyl



Q145 (a and b)
—OH
—H



Q146 (a and b)
—OH
-tert-butyl



Q147 (a and b)
—OH
-iso-butyl



Q148 (a and b)
—OH
-sec-butyl



Q149 (a and b)
—OH
-iso-propyl



Q150 (a and b)
—OH
-n-propyl



Q151 (a and b)
—OH
-cyclohexyl



Q152 (a and b)
—OH
-tert-butoxy



Q153 (a and b)
—OH
-isopropoxy



Q154 (a and b)
—OH
—CF3



Q155 (a and b)
—OH
—CH2CF3



Q156 (a and b)
—OH
—OCF3



Q157 (a and b)
—OH
—Cl



Q158 (a and b)
—OH
—Br



Q159 (a and b)
—OH
—I



Q160 (a and b)
—OH
-n-butyl



Q161 (a and b)
—OH
—CH3



Q162 (a and b)
—OH
—SCF3



Q163 (a and b)
—OH
—N(CH2CH3)2



Q164 (a and b)
—OH
—OCF2CHF2



Q165 (a and b)
—OH
—C(OH)(CF3)2



Q166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



Q167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



Q168 (a and b)
—OH
—N-piperidinyl



Q169 (a and b)
—NO2
—H



Q170 (a and b)
—NO2
-tert-butyl



Q171 (a and b)
—NO2
-iso-butyl



Q172 (a and b)
—NO2
-sec-butyl



Q173 (a and b)
—NO2
-iso-propyl



Q174 (a and b)
—NO2
-n-propyl



Q175 (a and b)
—NO2
-cyclohexyl



Q176 (a and b)
—NO2
-tert-butoxy



Q177 (a and b)
—NO2
-isopropoxy



Q178 (a and b)
—NO2
—CF3



Q179 (a and b)
—NO2
—CH2CF3



Q180 (a and b)
—NO2
—OCF3



Q181 (a and b)
—NO2
—Cl



Q182 (a and b)
—NO2
—Br



Q183 (a and b)
—NO2
—I



Q184 (a and b)
—NO2
-n-butyl



Q185 (a and b)
—NO2
—CH3



Q186 (a and b)
—NO2
—SCF3



Q187 (a and b)
—NO2
—N(CH2CH3)2



Q188 (a and b)
—NO2
—OCF2CHF2



Q189 (a and b)
—NO2
—C(OH)(CF3)2



Q190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



Q191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



Q192 (a and b)
—NO2
—N-piperidinyl



Q193 (a and b)
—CN
—H



Q194 (a and b)
—CN
-tert-butyl



Q195 (a and b)
—CN
-iso-butyl



Q196 (a and b)
—CN
-sec-butyl



Q197 (a and b)
—CN
-iso-propyl



Q198 (a and b)
—CN
-n-propyl



Q199 (a and b)
—CN
-cyclohexyl



Q200 (a and b)
—CN
-tert-butoxy



Q201 (a and b)
—CN
-isopropoxy



Q202 (a and b)
—CN
—CF3



Q203 (a and b)
—CN
—CH2CF3



Q204 (a and b)
—CN
—OCF3



Q205 (a and b)
—CN
—Cl



Q206 (a and b)
—CN
—Br



Q207 (a and b)
—CN
—I



Q208 (a and b)
—CN
-n-butyl



Q209 (a and b)
—CN
—CH3



Q210 (a and b)
—CN
—SCF3



Q211 (a and b)
—CN
—N(CH2CH3)2



Q212 (a and b)
—CN
—OCF2CHF2



Q213 (a and b)
—CN
—C(OH)(CF3)2



Q214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



Q215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



Q216 (a and b)
—CN
—N-piperidinyl



Q217 (a and b)
—Br
—H



Q218 (a and b)
—Br
-tert-butyl



Q219 (a and b)
—Br
-iso-butyl



Q220 (a and b)
—Br
-sec-butyl



Q221 (a and b)
—Br
-iso-propyl



Q222 (a and b)
—Br
-n-propyl



Q223 (a and b)
—Br
-cyclohexyl



Q224 (a and b)
—Br
-tert-butoxy



Q225 (a and b)
—Br
-isopropoxy



Q226 (a and b)
—Br
—CF3



Q227 (a and b)
—Br
—CH2CF3



Q228 (a and b)
—Br
—OCF3



Q229 (a and b)
—Br
—Cl



Q230 (a and b)
—Br
—Br



Q231 (a and b)
—Br
—I



Q232 (a and b)
—Br
-n-butyl



Q233 (a and b)
—Br
—CH3



Q234 (a and b)
—Br
—SCF3



Q235 (a and b)
—Br
—N(CH2CH3)2



Q236 (a and b)
—Br
—OCF2CHF2



Q237 (a and b)
—Br
—C(OH)(CF3)2



Q238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



Q239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



Q240 (a and b)
—Br
—N-piperidinyl



Q241 (a and b)
—I
-tert-butyl



Q242 (a and b)
—I
—H



Q243 (a and b)
—I
-iso-butyl



Q244 (a and b)
—I
-sec-butyl



Q245 (a and b)
—I
-iso-propyl



Q246 (a and b)
—I
-n-propyl



Q247 (a and b)
—I
-cyclohexyl



Q248 (a and b)
—I
-tert-butoxy



Q249 (a and b)
—I
-isopropoxy



Q250 (a and b)
—I
—CF3



Q251 (a and b)
—I
—CH2CF3



Q252 (a and b)
—I
—OCF3



Q253 (a and b)
—I
—Cl



Q254 (a and b)
—I
—Br



Q255 (a and b)
—I
—I



Q256 (a and b)
—I
-n-butyl



Q257 (a and b)
—I
—CH3



Q258 (a and b)
—I
—SCF3



Q259 (a and b)
—I
—N(CH2CH3)2



Q260 (a and b)
—I
—OCF2CHF2



Q261 (a and b)
—I
—C(OH)(CF3)2



Q262 (a and b)
—I
-(1,1-dimethyl-pentyl)



Q263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



Q264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.













TABLE 18







(Ir)




embedded image







and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






R1 (a and b)
—H
—H



R2 (a and b)
—H
-tert-butyl



R3 (a and b)
—H
-iso-butyl



R4 (a and b)
—H
-sec-butyl



R5 (a and b)
—H
-iso-propyl



R6 (a and b)
—H
-n-propyl



R7 (a and b)
—H
-cyclohexyl



R8 (a and b)
—H
-tert-butoxy



R9 (a and b)
—H
-isopropoxy



R10 (a and b)
—H
—CF3



R11 (a and b)
—H
—CH2CF3



R12 (a and b)
—H
—OCF3



R13 (a and b)
—H
—Cl



R14 (a and b)
—H
—Br



R15 (a and b)
—H
—I



R16 (a and b)
—H
-n-butyl



R17 (a and b)
—H
—CH3



R18 (a and b)
—H
—SCF3



R19 (a and b)
—H
—N(CH2CH3)2



R20 (a and b)
—H
—OCF2CHF2



R21 (a and b)
—H
—C(OH)(CF3)2



R22 (a and b)
—H
-(1,1-dimethyl-pentyl)



R23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



R24 (a and b)
—H
—N-piperidinyl



R25 (a and b)
—Cl
—H



R26 (a and b)
—Cl
-tert-butyl



R27 (a and b)
—Cl
-iso-butyl



R28 (a and b)
—Cl
-sec-butyl



R29 (a and b)
—Cl
-iso-propyl



R30 (a and b)
—Cl
-n-propyl



R31 (a and b)
—Cl
-cyclohexyl



R32 (a and b)
—Cl
-tert-butoxy



R33 (a and b)
—Cl
-isopropoxy



R34 (a and b)
—Cl
—CF3



R35 (a and b)
—Cl
—CH2CF3



R36 (a and b)
—Cl
—OCF3



R37 (a and b)
—Cl
—Cl



R38 (a and b)
—Cl
—Br



R39 (a and b)
—Cl
—I



R40 (a and b)
—Cl
-n-butyl



R41 (a and b)
—Cl
—CH3



R42 (a and b)
—Cl
—SCF3



R43 (a and b)
—Cl
—N(CH2CH3)2



R44 (a and b)
—Cl
—OCF2CHF2



R45 (a and b)
—Cl
—C(OH)(CF3)2



R46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



R47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



R48 (a and b)
—Cl
—N-piperidinyl



R49 (a and b)
—F
—H



R50 (a and b)
—F
-tert-butyl



R51 (a and b)
—F
-iso-butyl



R52 (a and b)
—F
-sec-butyl



R53 (a and b)
—F
-iso-propyl



R54 (a and b)
—F
-n-propyl



R55 (a and b)
—F
-cyclohexyl



R56 (a and b)
—F
-tert-butoxy



R57 (a and b)
—F
-isopropoxy



R58 (a and b)
—F
—CF3



R59 (a and b)
—F
—CH2CF3



R60 (a and b)
—F
—OCF3



R61 (a and b)
—F
—Cl



R62 (a and b)
—F
—Br



R63 (a and b)
—F
—I



R64 (a and b)
—F
-n-butyl



R65 (a and b)
—F
—CH3



R66 (a and b)
—F
—SCF3



R67 (a and b)
—F
—N(CH2CH3)2



R68 (a and b)
—F
—OCF2CHF2



R69 (a and b)
—F
—C(OH)(CF3)2



R70 (a and b)
—F
-(1,1-dimethyl-pentyl)



R71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



R72 (a and b)
—F
—N-piperidinyl



R73 (a and b)
—CH3
—H



R74 (a and b)
—CH3
-iso-butyl



R75 (a and b)
—CH3
-tert-butyl



R76 (a and b)
—CH3
-sec-butyl



R77 (a and b)
—CH3
-iso-propyl



R78 (a and b)
—CH3
-n-propyl



R79 (a and b)
—CH3
-cyclohexyl



R80 (a and b)
—CH3
-tert-butoxy



R81 (a and b)
—CH3
-isopropoxy



R82 (a and b)
—CH3
—CF3



R83 (a and b)
—CH3
—CH2CF3



R84 (a and b)
—CH3
—OCF3



R85 (a and b)
—CH3
—Cl



R86 (a and b)
—CH3
—Br



R87 (a and b)
—CH3
—I



R88 (a and b)
—CH3
-n-butyl



R89 (a and b)
—CH3
—CH3



R90 (a and b)
—CH3
—SCF3



R91 (a and b)
—CH3
—N(CH2CH3)2



R92 (a and b)
—CH3
—OCF2CHF2



R93 (a and b)
—CH3
—C(OH)(CF3)2



R94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



R95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



R96 (a and b)
—CH3
—N-piperidinyl



R97 (a and b)
—CF3
—H



R98 (a and b)
—CF3
-tert-butyl



R99 (a and b)
—CF3
-iso-butyl



R100 (a and b)
—CF3
-sec-butyl



R101 (a and b)
—CF3
-iso-propyl



R102 (a and b)
—CF3
-n-propyl



R103 (a and b)
—CF3
-cyclohexyl



R104 (a and b)
—CF3
-tert-butoxy



R105 (a and b)
—CF3
-isopropoxy



R106 (a and b)
—CF3
—CF3



R107 (a and b)
—CF3
—CH2CF3



R108 (a and b)
—CF3
—OCF3



R109 (a and b)
—CF3
—Cl



R110 (a and b)
—CF3
—Br



R111 (a and b)
—CF3
—I



R112 (a and b)
—CF3
-n-butyl



R113 (a and b)
—CF3
—CH3



R114 (a and b)
—CF3
—SCF3



R115 (a and b)
—CF3
—N(CH2CH3)2



R116 (a and b)
—CF3
—OCF2CHF2



R117 (a and b)
—CF3
—C(OH)(CF3)2



R118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



R119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



R120 (a and b)
—CF3
—N-piperidinyl



R121 (a and b)
—CHF2
-tert-butyl



R122 (a and b)
—CHF2
—H



R123 (a and b)
—CHF2
-iso-butyl



R124 (a and b)
—CHF2
-sec-butyl



R125 (a and b)
—CHF2
-iso-propyl



R126 (a and b)
—CHF2
-n-propyl



R127 (a and b)
—CHF2
-cyclohexyl



R128 (a and b)
—CHF2
-tert-butoxy



R129 (a and b)
—CHF2
-isopropoxy



R130 (a and b)
—CHF2
—CF3



R131 (a and b)
—CHF2
—CH2CF3



R132 (a and b)
—CHF2
—OCF3



R133 (a and b)
—CHF2
—Cl



R134 (a and b)
—CHF2
—Br



R135 (a and b)
—CHF2
—I



R136 (a and b)
—CHF2
-n-butyl



R137 (a and b)
—CHF2
—CH3



R138 (a and b)
—CHF2
—SCF3



R139 (a and b)
—CHF2
—N(CH2CH3)2



R140 (a and b)
—CHF2
—OCF2CHF2



R141 (a and b)
—CHF2
—C(OH)(CF3)2



R142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



R143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



R144 (a and b)
—CHF2
—N-piperidinyl



R145 (a and b)
—OH
—H



R146 (a and b)
—OH
-tert-butyl



R147 (a and b)
—OH
-iso-butyl



R148 (a and b)
—OH
-sec-butyl



R149 (a and b)
—OH
-iso-propyl



R150 (a and b)
—OH
-n-propyl



R151 (a and b)
—OH
-cyclohexyl



R152 (a and b)
—OH
-tert-butoxy



R153 (a and b)
—OH
-isopropoxy



R154 (a and b)
—OH
—CF3



R155 (a and b)
—OH
—CH2CF3



R156 (a and b)
—OH
—OCF3



R157 (a and b)
—OH
—Cl



R158 (a and b)
—OH
—Br



R159 (a and b)
—OH
—I



R160 (a and b)
—OH
-n-butyl



R161 (a and b)
—OH
—CH3



R162 (a and b)
—OH
—SCF3



R163 (a and b)
—OH
—N(CH2CH3)2



R164 (a and b)
—OH
—OCF2CHF2



R165 (a and b)
—OH
—C(OH)(CF3)2



R166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



R167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



R168 (a and b)
—OH
—N-piperidinyl



R169 (a and b)
—NO2
—H



R170 (a and b)
—NO2
-tert-butyl



R171 (a and b)
—NO2
-iso-butyl



R172 (a and b)
—NO2
-sec-butyl



R173 (a and b)
—NO2
-iso-propyl



R174 (a and b)
—NO2
-n-propyl



R175 (a and b)
—NO2
-cyclohexyl



R176 (a and b)
—NO2
-tert-butoxy



R177 (a and b)
—NO2
-isopropoxy



R178 (a and b)
—NO2
—CF3



R179 (a and b)
—NO2
—CH2CF3



R180 (a and b)
—NO2
—OCF3



R181 (a and b)
—NO2
—Cl



R182 (a and b)
—NO2
—Br



R183 (a and b)
—NO2
—I



R184 (a and b)
—NO2
-n-butyl



R185 (a and b)
—NO2
—CH3



R186 (a and b)
—NO2
—SCF3



R187 (a and b)
—NO2
—N(CH2CH3)2



R188 (a and b)
—NO2
—OCF2CHF2



R189 (a and b)
—NO2
—C(OH)(CF3)2



R190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



R191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



R192 (a and b)
—NO2
—N-piperidinyl



R193 (a and b)
—CN
—H



R194 (a and b)
—CN
-tert-butyl



R195 (a and b)
—CN
-iso-butyl



R196 (a and b)
—CN
-sec-butyl



R197 (a and b)
—CN
-iso-propyl



R198 (a and b)
—CN
-n-propyl



R199 (a and b)
—CN
-cyclohexyl



R200 (a and b)
—CN
-tert-butoxy



R201 (a and b)
—CN
-isopropoxy



R202 (a and b)
—CN
—CF3



R203 (a and b)
—CN
—CH2CF3



R204 (a and b)
—CN
—OCF3



R205 (a and b)
—CN
—Cl



R206 (a and b)
—CN
—Br



R207 (a and b)
—CN
—I



R208 (a and b)
—CN
-n-butyl



R209 (a and b)
—CN
—CH3



R210 (a and b)
—CN
—SCF3



R211 (a and b)
—CN
—N(CH2CH3)2



R212 (a and b)
—CN
—OCF2CHF2



R213 (a and b)
—CN
—C(OH)(CF3)2



R214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



R215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



R216 (a and b)
—CN
—N-piperidinyl



R217 (a and b)
—Br
—H



R218 (a and b)
—Br
-tert-butyl



R219 (a and b)
—Br
-iso-butyl



R220 (a and b)
—Br
-sec-butyl



R221 (a and b)
—Br
-iso-propyl



R222 (a and b)
—Br
-n-propyl



R223 (a and b)
—Br
-cyclohexyl



R224 (a and b)
—Br
-tert-butoxy



R225 (a and b)
—Br
-isopropoxy



R226 (a and b)
—Br
—CF3



R227 (a and b)
—Br
—CH2CF3



R228 (a and b)
—Br
—OCF3



R229 (a and b)
—Br
—Cl



R230 (a and b)
—Br
—Br



R231 (a and b)
—Br
—I



R232 (a and b)
—Br
-n-butyl



R233 (a and b)
—Br
—CH3



R234 (a and b)
—Br
—SCF3



R235 (a and b)
—Br
—N(CH2CH3)2



R236 (a and b)
—Br
—OCF2CHF2



R237 (a and b)
—Br
—C(OH)(CF3)2



R238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



R239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



R240 (a and b)
—Br
—N-piperidinyl



R241 (a and b)
—I
-tert-butyl



R242 (a and b)
—I
—H



R243 (a and b)
—I
-iso-butyl



R244 (a and b)
—I
-sec-butyl



R245 (a and b)
—I
-iso-propyl



R246 (a and b)
—I
-n-propyl



R247 (a and b)
—I
-cyclohexyl



R248 (a and b)
—I
-tert-butoxy



R249 (a and b)
—I
-isopropoxy



R250 (a and b)
—I
—CF3



R251 (a and b)
—I
—CH2CF3



R252 (a and b)
—I
—OCF3



R253 (a and b)
—I
—Cl



R254 (a and b)
—I
—Br



R255 (a and b)
—I
—I



R256 (a and b)
—I
-n-butyl



R257 (a and b)
—I
—CH3



R258 (a and b)
—I
—SCF3



R259 (a and b)
—I
—N(CH2CH3)2



R260 (a and b)
—I
—OCF2CHF2



R261 (a and b)
—I
—C(OH)(CF3)2



R262 (a and b)
—I
-(1,1-dimethyl-pentyl)



R263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



R264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.













TABLE 19







(Is)




embedded image







and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






S1 (a and b)
—H
—H



S2 (a and b)
—H
-tert-butyl



S3 (a and b)
—H
-iso-butyl



S4 (a and b)
—H
-sec-butyl



S5 (a and b)
—H
-iso-propyl



S6 (a and b)
—H
-n-propyl



S7 (a and b)
—H
-cyclohexyl



S8 (a and b)
—H
-tert-butoxy



S9 (a and b)
—H
-isopropoxy



S10 (a and b)
—H
—CF3



S11 (a and b)
—H
—CH2CF3



S12 (a and b)
—H
—OCF3



S13 (a and b)
—H
—Cl



S14 (a and b)
—H
—Br



S15 (a and b)
—H
—I



S16 (a and b)
—H
-n-butyl



S17 (a and b)
—H
—CH3



S18 (a and b)
—H
—SCF3



S19 (a and b)
—H
—N(CH2CH3)2



S20 (a and b)
—H
—OCF2CHF2



S21 (a and b)
—H
—C(OH)(CF3)2



S22 (a and b)
—H
-(1,1-dimethyl-pentyl)



S23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



S24 (a and b)
—H
—N-piperidinyl



S25 (a and b)
—Cl
—H



S26 (a and b)
—Cl
-tert-butyl



S27 (a and b)
—Cl
-iso-butyl



S28 (a and b)
—Cl
-sec-butyl



S29 (a and b)
—Cl
-iso-propyl



S30 (a and b)
—Cl
-n-propyl



S31 (a and b)
—Cl
-cyclohexyl



S32 (a and b)
—Cl
-tert-butoxy



S33 (a and b)
—Cl
-isopropoxy



S34 (a and b)
—Cl
—CF3



S35 (a and b)
—Cl
—CH2CF3



S36 (a and b)
—Cl
—OCF3



S37 (a and b)
—Cl
—Cl



S38 (a and b)
—Cl
—Br



S39 (a and b)
—Cl
—I



S40 (a and b)
—Cl
-n-butyl



S41 (a and b)
—Cl
—CH3



S42 (a and b)
—Cl
—SCF3



S43 (a and b)
—Cl
—N(CH2CH3)2



S44 (a and b)
—Cl
—OCF2CHF2



S45 (a and b)
—Cl
—C(OH)(CF3)2



S46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



S47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



S48 (a and b)
—Cl
—N-piperidinyl



S49 (a and b)
—F
—H



S50 (a and b)
—F
-tert-butyl



S51 (a and b)
—F
-iso-butyl



S52 (a and b)
—F
-sec-butyl



S53 (a and b)
—F
-iso-propyl



S54 (a and b)
—F
-n-propyl



S55 (a and b)
—F
-cyclohexyl



S56 (a and b)
—F
-tert-butoxy



S57 (a and b)
—F
-isopropoxy



S58 (a and b)
—F
—CF3



S59 (a and b)
—F
—CH2CF3



S60 (a and b)
—F
—OCF3



S61 (a and b)
—F
—Cl



S62 (a and b)
—F
—Br



S63 (a and b)
—F
—I



S64 (a and b)
—F
-n-butyl



S65 (a and b)
—F
—CH3



S66 (a and b)
—F
—SCF3



S67 (a and b)
—F
—N(CH2CH3)2



S68 (a and b)
—F
—OCF2CHF2



S69 (a and b)
—F
—C(OH)(CF3)2



S70 (a and b)
—F
-(1,1-dimethyl-pentyl)



S71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



S72 (a and b)
—F
—N-piperidinyl



S73 (a and b)
—CH3
—H



S74 (a and b)
—CH3
-iso-butyl



S75 (a and b)
—CH3
-tert-butyl



S76 (a and b)
—CH3
-sec-butyl



S77 (a and b)
—CH3
-iso-propyl



S78 (a and b)
—CH3
-n-propyl



S79 (a and b)
—CH3
-cyclohexyl



S80 (a and b)
—CH3
-tert-butoxy



S81 (a and b)
—CH3
-isopropoxy



S82 (a and b)
—CH3
—CF3



S83 (a and b)
—CH3
—CH2CF3



S84 (a and b)
—CH3
—OCF3



S85 (a and b)
—CH3
—Cl



S86 (a and b)
—CH3
—Br



S87 (a and b
—CH3
—I



S88 (a and b)
—CH3
-n-butyl



S89 (a and b)
—CH3
—CH3



S90 (a and b)
—CH3
—SCF3



S91 (a and b)
—CH3
—N(CH2CH3)2



S92 (a and b)
—CH3
—OCF2CHF2



S93 (a and b)
—CH3
—C(OH)(CF3)2



S94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



S95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



S96 (a and b)
—CH3
—N-piperidinyl



S97 (a and b)
—CF3
—H



S98 (a and b)
—CF3
-tert-butyl



S99 (a and b)
—CF3
-iso-butyl



S100 (a and b)
—CF3
-sec-butyl



S101 (a and b)
—CF3
-iso-propyl



S102 (a and b)
—CF3
-n-propyl



S103 (a and b)
—CF3
-cyclohexyl



S104 (a and b)
—CF3
-tert-butoxy



S105 (a and b)
—CF3
-isopropoxy



S106 (a and b)
—CF3
—CF3



S107 (a and b)
—CF3
—CH2CF3



S108 (a and b)
—CF3
—OCF3



S109 (a and b)
—CF3
—Cl



S110 (a and b)
—CF3
—Br



S111 (a and b)
—CF3
—I



S112 (a and b)
—CF3
-n-butyl



S113 (a and b)
—CF3
—CH3



S114 (a and b)
—CF3
—SCF3



S115 (a and b)
—CF3
—N(CH2CH3)2



S116 (a and b)
—CF3
—OCF2CHF2



S117 (a and b)
—CF3
—C(OH)(CF3)2



S118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



S119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



S120 (a and b)
—CF3
—N-piperidinyl



S121 (a and b)
—CHF2
-tert-butyl



S122 (a and b)
—CHF2
—H



S123 (a and b)
—CHF2
-iso-butyl



S124 (a and b)
—CHF2
-sec-butyl



S125 (a and b)
—CHF2
-iso-propyl



S126 (a and b)
—CHF2
-n-propyl



S127 (a and b)
—CHF2
-cyclohexyl



S128 (a and b)
—CHF2
-tert-butoxy



S129 (a and b)
—CHF2
-isopropoxy



S130 (a and b)
—CHF2
—CF3



S131 (a and b)
—CHF2
—CH2CF3



S132 (a and b)
—CHF2
—OCF3



S133 (a and b)
—CHF2
—Cl



S134 (a and b)
—CHF2
—Br



S135 (a and b)
—CHF2
—I



S136 (a and b)
—CHF2
-n-butyl



S137 (a and b)
—CHF2
—CH3



S138 (a and b)
—CHF2
—SCF3



S139 (a and b)
—CHF2
—N(CH2CH3)2



S140 (a and b)
—CHF2
—OCF2CHF2



S141 (a and b)
—CHF2
—C(OH)(CF3)2



S142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



S143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



S144 (a and b)
—CHF2
—N-piperidinyl



S145 (a and b)
—OH
—H



S146 (a and b)
—OH
-tert-butyl



S147 (a and b)
—OH
-iso-butyl



S148 (a and b)
—OH
-sec-butyl



S149 (a and b)
—OH
-iso-propyl



S150 (a and b)
—OH
-n-propyl



S151 (a and b)
—OH
-cyclohexyl



S152 (a and b)
—OH
-tert-butoxy



S153 (a and b)
—OH
-isopropoxy



S154 (a and b)
—OH
—CF3



S155 (a and b)
—OH
—CH2CF3



S156 (a and b)
—OH
—OCF3



S157 (a and b)
—OH
—Cl



S158 (a and b)
—OH
—Br



S159 (a and b)
—OH
—I



S160 (a and b)
—OH
-n-butyl



S161 (a and b)
—OH
—CH3



S162 (a and b)
—OH
—SCF3



S163 (a and b)
—OH
—N(CH2CH3)2



S164 (a and b)
—OH
—OCF2CHF2



S165 (a and b)
—OH
—C(OH)(CF3)2



S166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



S167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



S168 (a and b)
—OH
—N-piperidinyl



S169 (a and b)
—NO2
—H



S170 (a and b)
—NO2
-tert-butyl



S171 (a and b)
—NO2
-iso-butyl



S172 (a and b)
—NO2
-sec-butyl



S173 (a and b)
—NO2
-iso-propyl



S174 (a and b)
—NO2
-n-propyl



S175 (a and b)
—NO2
-cyclohexyl



S176 (a and b)
—NO2
-tert-butoxy



S177 (a and b)
—NO2
-isopropoxy



S178 (a and b)
—NO2
—CF3



S179 (a and b)
—NO2
—CH2CF3



S180 (a and b)
—NO2
—OCF3



S181 (a and b)
—NO2
—Cl



S182 (a and b)
—NO2
—Br



S183 (a and b)
—NO2
—I



S184 (a and b)
—NO2
-n-butyl



S185 (a and b)
—NO2
—CH3



S186 (a and b)
—NO2
—SCF3



S187 (a and b)
—NO2
—N(CH2CH3)2



S188 (a and b)
—NO2
—OCF2CHF2



S189 (a and b)
—NO2
—C(OH)(CF3)2



S190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



S191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



S192 (a and b)
—NO2
—N-piperidinyl



S193 (a and b)
—CN
—H



S194 (a and b)
—CN
-tert-butyl



S195 (a and b)
—CN
-iso-butyl



S196 (a and b)
—CN
-sec-butyl



S197 (a and b)
—CN
-iso-propyl



S198 (a and b)
—CN
-n-propyl



S199 (a and b)
—CN
-cyclohexyl



S200 (a and b)
—CN
-tert-butoxy



S201 (a and b)
—CN
-isopropoxy



S202 (a and b)
—CN
—CF3



S203 (a and b)
—CN
—CH2CF3



S204 (a and b)
—CN
—OCF3



S205 (a and b)
—CN
—Cl



S206 (a and b)
—CN
—Br



S207 (a and b)
—CN
—I



S208 (a and b)
—CN
-n-butyl



S209 (a and b)
—CN
—CH3



S210 (a and b)
—CN
—SCF3



S211 (a and b)
—CN
—N(CH2CH3)2



S212 (a and b)
—CN
—OCF2CHF2



S213 (a and b)
—CN
—C(OH)(CF3)2



S214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



S215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



S216 (a and b)
—CN
—N-piperidinyl



S217 (a and b)
—Br
—H



S218 (a and b)
—Br
-tert-butyl



S219 (a and b)
—Br
-iso-butyl



S220 (a and b)
—Br
-sec-butyl



S221 (a and b)
—Br
-iso-propyl



S222 (a and b)
—Br
-n-propyl



S223 (a and b)
—Br
-cyclohexyl



S224 (a and b)
—Br
-tert-butoxy



S225 (a and b)
—Br
-isopropoxy



S226 (a and b)
—Br
—CF3



S227 (a and b)
—Br
—CH2CF3



S228 (a and b)
—Br
—OCF3



S229 (a and b)
—Br
—Cl



S230 (a and b)
—Br
—Br



S231 (a and b)
—Br
—I



S232 (a and b)
—Br
-n-butyl



S233 (a and b)
—Br
—CH3



S234 (a and b)
—Br
—SCF3



S235 (a and b)
—Br
—N(CH2CH3)2



S236 (a and b)
—Br
—OCF2CHF2



S237 (a and b)
—Br
—C(OH)(CF3)2



S238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



S239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



S240 (a and b)
—Br
—N-piperidinyl



S241 (a and b)
—I
-tert-butyl



S242 (a and b)
—I
—H



S243 (a and b)
—I
-iso-butyl



S244 (a and b)
—I
-sec-butyl



S245 (a and b)
—I
-iso-propyl



S246 (a and b)
—I
-n-propyl



S247 (a and b)
—I
-cyclohexyl



S248 (a and b)
—I
-tert-butoxy



S249 (a and b)
—I
-isopropoxy



S250 (a and b)
—I
—CF3



S251 (a and b)
—I
—CH2CF3



S252 (a and b)
—I
—OCF3



S253 (a and b)
—I
—Cl



S254 (a and b)
—I
—Br



S255 (a and b)
—I
—I



S256 (a and b)
—I
-n-butyl



S257 (a and b)
—I
—CH3



S258 (a and b)
—I
—SCF3



S259 (a and b)
—I
—N(CH2CH3)2



S260 (a and b)
—I
—OCF2CHF2



S261 (a and b)
—I
—C(OH)(CF3)2



S262 (a and b)
—I
-(1,1-dimethyl-pentyl)



S263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



S264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.













TABLE 20







(It)




embedded image







and pharmaceutically acceptable salts thereof, wherein:











Compound
Y
R1
(R8)a
(R8)b





T1 (a and b)
S
—H
—Cl
—H


T2 (a and b)
S
—H
—Br
—H


T3 (a and b)
S
—H
—F
—H


T4 (a and b)
S
—H
—CH3
—H


T5 (a and b)
S
—H
—CF3
—H


T6 (a and b)
S
—H
—OCH3
—H


T7 (a and b)
S
—H
—OCH2CH3
—H


T8 (a and b)
S
—H
—OCF3
—H


T9 (a and b)
S
—H
-tert-butyl
—H


T10 (a and b)
S
—H
-iso-propyl
—H


T11 (a and b)
S
—H
—CH3
—CH3


T12 (a and b)
S
—H
—H
—H


T13 (a and b)
S
—H
—H
—Cl


T14 (a and b)
S
—H
—H
—Br


T15 (a and b)
S
—H
—H
—F


T16 (a and b)
S
—H
—H
—CH3


T17 (a and b)
S
—H
—H
—CF3


T18 (a and b)
S
—H
—H
—OCH3


T19 (a and b)
S
—H
—H
—OCH2CH3


T20 (a and b)
S
—H
—H
—OCF3


T21 (a and b)
S
—H
—H
-tert-butyl


T22 (a and b)
S
—H
—H
-iso-propyl


T23 (a and b)
S
—Cl
—Cl
—H


T24 (a and b)
S
—Cl
—Br
—H


T25 (a and b)
S
—Cl
—F
—H


T26 (a and b)
S
—Cl
—CH3
—H


T27 (a and b)
S
—Cl
—CF3
—H


T28 (a and b)
S
—Cl
—OCH3
—H


T29 (a and b)
S
—Cl
—OCH2CH3
—H


T30 (a and b)
S
—Cl
—OCF3
—H


T31 (a and b)
S
—Cl
-tert-butyl
—H


T32 (a and b)
S
—Cl
-iso-propyl
—H


T33 (a and b)
S
—Cl
—CH3
—CH3


T34 (a and b)
S
—Cl
—H
—H


T35 (a and b)
S
—Cl
—H
—Cl


T36 (a and b)
S
—Cl
—H
—Br


T37 (a and b)
S
—Cl
—H
—F


T38 (a and b)
S
—Cl
—H
—CH3


T39 (a and b)
S
—Cl
—H
—CF3


T40 (a and b)
S
—Cl
—H
—OCH3


T41 (a and b)
S
—Cl
—H
—OCH2CH3


T42 (a and b)
S
—Cl
—H
—OCF3


T43 (a and b)
S
—Cl
—H
-tert-butyl


T44 (a and b)
S
—Cl
—H
-iso-propyl


T45 (a and b)
S
—Cl
—H
—OCF3


T46 (a and b)
S
—Cl
—H
-tert-butyl


T47 (a and b)
S
—Cl
—H
-iso-propyl


T48 (a and b)
S
—CH3
—Cl
—H


T49 (a and b)
S
—CH3
—Br
—H


T50 (a and b)
S
—CH3
—F
—H


T51 (a and b)
S
—CH3
—CH3
—H


T52 (a and b)
S
—CH3
—CF3
—H


T53 (a and b)
S
—CH3
—OCH3
—H


T54 (a and b)
S
—CH3
—OCH2CH3
—H


T55 (a and b)
S
—CH3
—OCF3
—H


T56 (a and b)
S
—CH3
-tert-butyl
—H


T57 (a and b)
S
—CH3
-iso-propyl
—H


T58 (a and b)
S
—CH3
—CH3
—CH3


T59 (a and b)
S
—CH3
—H
—H


T60 (a and b)
S
—CH3
—H
—Cl


T61 (a and b)
S
—CH3
—H
—Br


T62 (a and b)
S
—CH3
—H
—F


T63 (a and b)
S
—CH3
—H
—CH3


T64 (a and b)
S
—CH3
—H
—CF3


T65 (a and b)
S
—CH3
—H
—OCH3


T66 (a and b)
S
—CH3
—H
—OCH2CH3


T67 (a and b)
S
—CH3
—H
—OCF3


T68 (a and b)
S
—CH3
—H
-tert-butyl


T69 (a and b)
S
—CH3
—H
-iso-propyl


T70 (a and b)
S
—CF3
—Cl
—H


T71 (a and b)
S
—CF3
—Br
—H


T72 (a and b)
S
—CF3
—F
—H


T73 (a and b)
S
—CF3
—CH3
—H


T74 (a and b)
S
—CF3
—CF3
—H


T75 (a and b)
S
—CF3
—OCH3
—H


T76 (a and b)
S
—CF3
—OCH2CH3
—H


T77 (a and b)
S
—CF3
—OCF3
—H


T78 (a and b)
S
—CF3
-tert-butyl
—H


T79 (a and b)
S
—CF3
-iso-propyl
—H


T80 (a and b)
S
—CF3
—CH3
—CH3


T81 (a and b)
S
—CF3
—H
—H


T82 (a and b)
S
—CF3
—H
—Cl


T83 (a and b)
S
—CF3
—H
—Br


T84 (a and b)
S
—CF3
—H
—F


T85 (a and b)
S
—CF3
—H
—CH3


T86 (a and b)
S
—CF3
—H
—CF3


T87 (a and b)
S
—CF3
—H
—OCH3


T88 (a and b)
S
—CF3
—H
—OCH2CH3


T89 (a and b)
S
—CF3
—H
—OCF3


T90 (a and b)
S
—CF3
—H
-tert-butyl


T91 (a and b)
S
—CF3
—H
-iso-propyl


T92 (a and b)
S
—CHF2
—Cl
—H


T93 (a and b)
S
—CHF2
—Br
—H


T94 (a and b)
S
—CHF2
—F
—H


T95 (a and b)
S
—CHF2
—CH3
—H


T96 (a and b)
S
—CHF2
—CF3
—H


T97 (a and b)
S
—CHF2
—OCH3
—H


T98 (a and b)
S
—CHF2
—OCH2CH3
—H


T99 (a and b)
S
—CHF2
—OCF3
—H


T100 (a and b)
S
—CHF2
-tert-butyl
—H


T101 (a and b)
S
—CHF2
-iso-propyl
—H


T102 (a and b)
S
—CHF2
—CH3
—CH3


T103 (a and b)
S
—CHF2
—H
—H


T104 (a and b)
S
—CHF2
—H
—Cl


T105 (a and b)
S
—CHF2
—H
—Br


T106 (a and b)
S
—CHF2
—H
—F


T107 (a and b)
S
—CHF2
—H
—CH3


T108 (a and b)
S
—CHF2
—H
—CF3


T109 (a and b)
S
—CHF2
—H
—OCH3


T110 (a and b)
S
—CHF2
—H
—OCH2CH3


T111 (a and b)
S
—CHF2
—H
—OCF3


T112 (a and b)
S
—CHF2
—H
-tert-butyl


T113 (a and b)
S
—CHF2
—H
-iso-propyl


T114 (a and b)
S
—OH
—Cl
—H


T115 (a and b)
S
—OH
—Br
—H


T116 (a and b)
S
—OH
—F
—H


T117 (a and b)
S
—OH
—CH3
—H


T118 (a and b)
S
—OH
—CF3
—H


T119 (a and b)
S
—OH
—OCH3
—H


T120 (a and b)
S
—OH
—OCH2CH3
—H


T121 (a and b)
S
—OH
—OCF3
—H


T122 (a and b)
S
—OH
-tert-butyl
—H


T123 (a and b)
S
—OH
-iso-propyl
—H


T124 (a and b)
S
—OH
—CH3
—CH3


T125 (a and b)
S
—OH
—H
—H


T126 (a and b)
S
—OH
—H
—Cl


T127 (a and b)
S
—OH
—H
—Br


T128 (a and b)
S
—OH
—H
—F


T129 (a and b)
S
—OH
—H
—CH3


T130 (a and b)
S
—OH
—H
—CF3


T131 (a and b)
S
—OH
—H
—OCH3


T132 (a and b)
S
—OH
—H
—OCH2CH3


T133 (a and b)
S
—OH
—H
—OCF3


T134 (a and b)
S
—OH
—H
-tert-butyl


T135 (a and b)
S
—OH
—H
-iso-propyl


T136 (a and b)
S
—NO2
—Cl
—H


T137 (a and b)
S
—NO2
—F
—H


T139 (a and b)
S
—NO2
—CH3
—H


T140 (a and b)
S
—NO2
—CF3
—H


T141 (a and b)
S
—NO2
—OCH3
—H


T142 (a and b)
S
—NO2
—OCH2CH3
—H


T143 (a and b)
S
—NO2
—OCF3
—H


T144 (a and b)
S
—NO2
-tert-butyl
—H


T145 (a and b)
S
—NO2
-iso-propyl
—H


T146 (a and b)
S
—NO2
—CH3
—CH3


T147 (a and b)
S
—NO2
—H
—H


T148 (a and b)
S
—NO2
—H
—Cl


T149 (a and b)
S
—NO2
—H
—Br


T150 (a and b)
S
—NO2
—H
—F


T151 (a and b)
S
—NO2
—H
—CH3


T152 (a and b)
S
—NO2
—H
—CF3


T153 (a and b)
S
—NO2
—H
—OCH3


T154 (a and b)
S
—NO2
—H
—OCH2CH3


T155 (a and b)
S
—NO2
—H
—OCF3


T156 (a and b)
S
—NO2
—H
-tert-butyl


T157 (a and b)
S
—NO2
—H
-iso-propyl


T158 (a and b)
S
—CN
—Br
—H


T159 (a and b)
S
—CN
—Cl
—H


T160 (a and b)
S
—CN
—F
—H


T161 (a and b)
S
—CN
—CH3
—H


T162 (a and b)
S
—CN
—CF3
—H


T163 (a and b)
S
—CN
—OCH3
—H


T164 (a and b)
S
—CN
—OCH2CH3
—H


T165 (a and b)
S
—CN
—OCF3
—H


T166 (a and b)
S
—CN
-tert-butyl
—H


T167 (a and b)
S
—CN
-iso-propyl
—H


T168 (a and b)
S
—CN
—CH3
—CH3


T169 (a and b)
S
—CN
—H
—H


T170 (a and b)
S
—CN
—H
—Cl


T171 (a and b)
S
—CN
—H
—Br


T172 (a and b)
S
—CN
—H
—F


T173 (a and b)
S
—CN
—H
—CH3


T174 (a and b)
S
—CN
—H
—CF3


T175 (a and b)
S
—CN
—H
—OCH3


T176 (a and b)
S
—CN
—H
—OCH2CH3


T177 (a and b)
S
—CN
—H
—OCF3


T178 (a and b)
S
—CN
—H
-tert-butyl


T179 (a and b)
S
—CN
—H
-iso-propyl


T180 (a and b)
S
—Br
—Br
—H


T181 (a and b)
S
—Br
—Cl
—H


T182 (a and b)
S
—Br
—F
—H


T183 (a and b)
S
—Br
—CH3
—H


T184 (a and b)
S
—Br
—CF3
—H


T185 (a and b)
S
—Br
—OCH3
—H


T186 (a and b)
S
—Br
—OCH2CH3
—H


T187 (a and b)
S
—Br
—OCF3
—H


T188 (a and b)
S
—Br
-tert-butyl
—H


T189 (a and b)
S
—Br
-iso-propyl
—H


T190 (a and b)
S
—Br
—CH3
—CH3


T191 (a and b)
S
—Br
—H
—H


T192 (a and b)
S
—Br
—H
—Cl


T193 (a and b)
S
—Br
—H
—Br


T194 (a and b)
S
—Br
—H
—F


T195 (a and b)
S
—Br
—H
—CH3


TI96 (a and b)
S
—Br
—H
—CF3


T197 (a and b)
S
—Br
—H
—OCH3


TI98 (a and b)
S
—Br
—H
—OCH2CH3


T199 (a and b)
S
—Br
—H
—OCF3


T200 (a and b)
S
—Br
—H
-tert-butyl


T201 (a and b)
S
—Br
—H
-iso-propyl


T202 (a and b)
S
—I
—Cl
—H


T203 (a and b)
S
—I
—Br
—H


T204 (a and b)
S
—I
—F
—H


T205 (a and b)
S
—I
—CH3
—H


T206 (a and b)
S
—I
—CF3
—H


T207 (a and b)
S
—I
—OCH3
—H


T208 (a and b)
S
—I
—OCH2CH3
—H


T209 (a and b)
S
—I
—OCF3
—H


T210 (a and b)
S
—I
-tert-butyl
—H


T211 (a and b)
S
—I
-iso-propyl
—H


T212 (a and b)
S
—I
—CH3
—CH3


T213 (a and b)
S
—I
—H
—H


T214 (a and b)
S
—I
—H
—Cl


T215 (a and b)
S
—I
—H
—Br


T216 (a and b)
S
—I
—H
—F


T217 (a and b)
S
—I
—H
—CH3


T218 (a and b)
S
—I
—H
—CF3


T219 (a and b)
S
—I
—H
—OCH3


T220 (a and b)
S
—I
—H
—OCH2CH3


T221 (a and b)
S
—I
—H
—OCF3


T222 (a and b)
S
—I
—H
-tert-butyl


T223 (a and b)
S
—I
—H
-iso-propyl


T224 (a and b)
O
—H
—Cl
—H


T225 (a and b)
O
—H
—Br
—H


T226 (a and b)
O
—H
—F
—H


T227 (a and b)
O
—H
—CH3
—H


T228 (a and b)
O
—H
—CF3
—H


T229 (a and b)
O
—H
—OCH3
—H


T230 (a and b)
O
—H
—OCH2CH3
—H


T231 (a and b)
O
—H
—OCF3
—H


T232 (a and b)
O
—H
-tert-butyl
—H


T233 (a and b)
O
—H
-iso-propyl
—H


T234 (a and b)
O
—H
—CH3
—CH3


T235 (a and b)
O
—H
—H
—H


T236 (a and b)
O
—H
—H
—Cl


T237 (a and b)
O
—H
—H
—Br


T238 (a and b)
O
—H
—H
—F


T239 (a and b)
O
—H
—H
—CH3


T240 (a and b)
O
—H
—H
—CF3


T241 (a and b)
O
—H
—H
—OCH3


T242 (a and b)
O
—H
—H
—OCH2CH3


T243 (a and b)
O
—H
—H
—OCF3


T244 (a and b)
O
—H
—H
-tert-butyl


T245 (a and b)
O
—H
—H
-iso-propyl


T246 (a and b)
O
—Cl
—Cl
—H


T247 (a and b)
O
—Cl
—Br
—H


T248 (a and b)
O
—Cl
—F
—H


T249 (a and b)
O
—Cl
—CH3
—H


T250 (a and b)
O
—Cl
—CF3
—H


T251 (a and b)
O
—Cl
—OCH3
—H


T252 (a and b)
O
—Cl
—OCH2CH3
—H


T253 (a and b)
O
—Cl
—OCF3
—H


T254 (a and b)
O
—Cl
-tert-butyl
—H


T255 (a and b)
O
—Cl
-iso-propyl
—H


T256 (a and b)
O
—Cl
—CH3
—CH3


T257 (a and b)
O
—Cl
—H
—H


T258 (a and b)
O
—Cl
—H
—CH3


T259 (a and b)
O
—Cl
—H
—Cl


T260 (a and b)
O
—Cl
—H
—Br


T261 (a and b)
O
—Cl
—H
—F


T262 (a and b)
O
—Cl
—H
—CF3


T263 (a and b)
O
—Cl
—H
—OCH3


T264 (a and b)
O
—Cl
—H
—OCH2CH3


T265 (a and b)
O
—Cl
—H
—OCF3


T266 (a and b)
O
—Cl
—H
-tert-butyl


T267 (a and b)
O
—Cl
—H
-iso-propyl


T268 (a and b)
O
—Cl
—H
—OCF3


T269 (a and b)
O
—Cl
—H
-tert-butyl


T270 (a and b)
O
—Cl
—H
-iso-propyl


T271 (a and b)
O
—CH3
—Cl
—H


T272 (a and b)
O
—CH3
—Br
—H


T273 (a and b)
O
—CH3
—F
—H


T274 (a and b)
O
—CH3
—CH3
—H


T275 (a and b)
O
—CH3
—CF3
—H


T276 (a and b)
O
—CH3
—OCH3
—H


T277 (a and b)
O
—CH3
—OCH2CH3
—H


T278 (a and b)
O
—CH3
—OCF3
—H


T279 (a and b)
O
—CH3
-tert-butyl
—H


T280 (a and b)
O
—CH3
-iso-propyl
—H


T281 (a and b)
O
—CH3
—CH3
—CH3


T282 (a and b)
O
—CH3
—H
—H


T283 (a and b)
O
—CH3
—H
—Cl


T284 (a and b)
O
—CH3
—H
—Br


T285 (a and b)
O
—CH3
—H
—F


T286 (a and b)
O
—CH3
—H
—CH3


T287 (a and b)
O
—CH3
—H
—CF3


T288 (a and b)
O
—CH3
—H
—OCH3


T289 (a and b)
O
—CH3
—H
—OCH2CH3


T290 (a and b)
O
—CH3
—H
—OCF3


T291 (a and b)
O
—CH3
—H
-tert-butyl


T292 (a and b)
O
—CH3
—H
-iso-propyl


T293 (a and b)
O
—CF3
—Cl
—H


T294 (a and b)
O
—CF3
—Br
—H


T295 (a and b)
O
—CF3
—F
—H


T296 (a and b)
O
—CF3
—CH3
—H


T297 (a and b)
O
—CF3
—CF3
—H


T298 (a and b)
O
—CF3
—OCH3
—H


T299 (a and b)
O
—CF3
—OCH2CH3
—H


T300 (a and b)
O
—CF3
—OCF3
—H


T301 (a and b)
O
—CF3
-tert-butyl
—H


T302 (a and b)
O
—CF3
-iso-propyl
—H


T303 (a and b)
O
—CF3
—CH3
—CH3


T304 (a and b)
O
—CF3
—H
—H


T305 (a and b)
O
—CF3
—H
—Cl


T306 (a and b)
O
—CF3
—H
—Br


T307 (a and b)
O
—CF3
—H
—F


T308 (a and b)
O
—CF3
—H
—CH3


T309 (a and b)
O
—CF3
—H
—CF3


T310 (a and b)
O
—CF3
—H
—OCH3


T311 (a and b)
O
—CF3
—H
—OCH2CH3


T312 (a and b)
O
—CF3
—H
—OCF3


T313 (a and b)
O
—CF3
—H
-tert-butyl


T314 (a and b)
O
—CF3
—H
-iso-propyl


T315 (a and b)
O
—CHF2
—Cl
—H


T316 (a and b)
O
—CHF2
—Br
—H


T317 (a and b)
O
—CHF2
—F
—H


T318 (a and b)
O
—CHF2
—CH3
—H


T319 (a and b)
O
—CHF2
—CF3
—H


T320 (a and b)
O
—CHF2
—OCH3
—H


T321 (a and b)
O
—CHF2
—OCH2CH3
—H


T322 (a and b)
O
—CHF2
—OCF3
—H


T323 (a and b)
O
—CHF2
-tert-butyl
—H


T324 (a and b)
O
—CHF2
-iso-propyl
—H


T325 (a and b)
O
—CHF2
—CH3
—CH3


T326 (a and b)
O
—CHF2
—H
—H


T327 (a and b)
O
—CHF2
—H
—Cl


T328 (a and b)
O
—CHF2
—H
—Br


T329 (a and b)
O
—CHF2
—H
—F


T330 (a and b)
O
—CHF2
—H
—CH3


T331 (a and b)
O
—CHF2
—H
—CF3


T332 (a and b)
O
—CHF2
—H
—OCH3


T333 (a and b)
O
—CHF2
—H
—OCH2CH3


T334 (a and b)
O
—CHF2
—H
—OCF3


T335 (a and b)
O
—CHF2
—H
-tert-butyl


T336 (a and b)
O
—CHF2
—H
-iso-propyl


T337 (a and b)
O
—OH
—Cl
—H


T338 (a and b)
O
—OH
—Br
—H


T339 (a and b)
O
—OH
—F
—H


T340 (a and b)
O
—OH
—CH3
—H


T341 (a and b)
O
—OH
—CF3
—H


T342 (a and b)
O
—OH
—OCH3
—H


T343 (a and b)
O
—OH
—OCH2CH3
—H


T344 (a and b)
O
—OH
—OCF3
—H


T345 (a and b)
O
—OH
-tert-butyl
—H


T346 (a and b)
O
—OH
-iso-propyl
—H


T347 (a and b)
O
—OH
—CH3
—CH3


T348 (a and b)
O
—OH
—H
—H


T349 (a and b)
O
—OH
—H
—Cl


T350 (a and b)
O
—OH
—H
—Br


T351 (a and b)
O
—OH
—H
—F


T352 (a and b)
O
—OH
—H
—CH3


T353 (a and b)
O
—OH
—H
—CF3


T354 (a and b)
O
—OH
—H
—OCH3


T355 (a and b)
O
—OH
—H
—OCH2CH3


T356 (a and b)
O
—OH
—H
—OCF3


T357 (a and b)
O
—OH
—H
-tert-butyl


T358 (a and b)
O
—OH
—H
-iso-propyl


T359 (a and b)
O
—NO2
—Cl
—H


T360 (a and b)
O
—NO2
—Br
—H


T361 (a and b)
O
—NO2
—F
—H


T362 (a and b)
O
—NO2
—CH3
—H


T363 (a and b)
O
—NO2
—CF3
—H


T364 (a and b)
O
—NO2
—OCH3
—H


T365 (a and b)
O
—NO2
—OCH2CH3
—H


T366 (a and b)
O
—NO2
—OCF3
—H


T367 (a and b)
O
—NO2
-tert-butyl
—H


T368 (a and b)
O
—NO2
-iso-propyl
—H


T369 (a and b)
O
—NO2
—CH3
—CH3


T370 (a and b)
O
—NO2
—H
—H


T371 (a and b)
O
—NO2
—H
—Cl


T372 (a and b)
O
—NO2
—H
—Br


T373 (a and b)
O
—NO2
—H
—F


T374 (a and b)
O
—NO2
—H
—CH3


T375 (a and b)
O
—NO2
—H
—CF3


T376 (a and b)
O
—NO2
—H
—OCH3


T377 (a and b)
O
—NO2
—H
—OCH2CH3


T378 (a and b)
O
—NO2
—H
—OCF3


T379 (a and b)
O
—NO2
—H
-tert-butyl


T380 (a and b)
O
—NO2
—H
-iso-propyl


T381 (a and b)
O
—CN
—Br
—H


T382 (a and b)
O
—CN
—Cl
—H


T383 (a and b)
O
—CN
—F
—H


T384 (a and b)
O
—CN
—CH3
—H


T385 (a and b)
O
—CN
—CF3
—H


T386 (a and b)
O
—CN
—OCH3
—H


T387 (a and b)
O
—CN
—OCH2CH3
—H


T388 (a and b)
O
—CN
—OCF3
—H


T389 (a and b)
O
—CN
-tert-butyl
—H


T390 (a and b)
O
—CN
-iso-propyl
—H


T391 (a and b)
O
—CN
—CH3
—CH3


T392 (a and b)
O
—CN
—H
—H


T393 (a and b)
O
—CN
—H
—Cl


T394 (a and b)
O
—CN
—H
—Br


T395 (a and b)
O
—CN
—H
—F


T396 (a and b)
O
—CN
—H
—CH3


T397 (a and b)
O
—CN
—H
—CF3


T398 (a and b)
O
—CN
—H
—OCH3


T399 (a and b)
O
—CN
—H
—OCH2CH3


T400 (a and b)
O
—CN
—H
—OCF3


T401 (a and b)
O
—CN
—H
-tert-butyl


T402 (a and b)
O
—CN
—H
-iso-propyl


T403 (a and b)
O
—Br
—Br
—H


T404 (a and b)
O
—Br
—Cl
—H


T405 (a and b)
O
—Br
—F
—H


T406 (a and b)
O
—Br
—CH3
—H


T407 (a and b)
O
—Br
—CF3
—H


T408 (a and b)
O
—Br
—OCH3
—H


T409 (a and b)
O
—Br
—OCH2CH3
—H


T410 (a and b)
O
—Br
—OCF3
—H


T411 (a and b)
O
—Br
-tert-butyl
—H


T412 (a and b)
O
—Br
-iso-propyl
—H


T413 (a and b)
O
—Br
—CH3
—CH3


T414 (a and b)
O
—Br
—H
—H


T415 (a and b)
O
—Br
—H
—Cl


T416 (a and b)
O
—Br
—H
—Br


T417 (a and b)
O
—Br
—H
—F


T418 (a and b)
O
—Br
—H
—CH3


T419 (a and b)
O
—Br
—H
—CF3


T420 (a and b)
O
—Br
—H
—OCH3


T421 (a and b)
O
—Br
—H
—OCH2CH3


T422 (a and b)
O
—Br
—H
—OCF3


T423 (a and b)
O
—Br
—H
-tert-butyl


T424 (a and b)
O
—Br
—H
-iso-propyl


T425 (a and b)
O
—I
—Cl
—H


T426 (a and b)
O
—I
—Br
—H


T427 (a and b)
O
—I
—F
—H


T428 (a and b)
O
—I
—CH3
—H


T429 (a and b)
O
—I
—CF3
—H


T430 (a and b)
O
—I
—OCH3
—H


T431 (a and b)
O
—I
—OCH2CH3
—H


T432 (a and b)
O
—I
—OCF3
—H


T433 (a and b)
O
—I
-tert-butyl
—H


T434 (a and b)
O
—I
-iso-propyl
—H


T435 (a and b)
O
—I
—CH3
—CH3


T436 (a and b)
O
—I
—H
—H


T437 (a and b)
O
—I
—H
—Cl


T438 (a and b)
O
—I
—H
—Br


T439 (a and b)
O
—I
—H
—F


T440 (a and b)
O
—I
—H
—CH3


T441 (a and b)
O
—I
—H
—CF3


T442 (a and b)
O
—I
—H
—OCH3


T443 (a and b)
O
—I
—H
—OCH2CH3


T444 (a and b)
O
—I
—H
—OCF3


T445 (a and b)
O
—I
—H
-tert-butyl


T446 (a and b)
O
—I
—H
-iso-propyl


T447 (a and b)
NH
—H
—Cl
—H


T448 (a and b)
NH
—H
—Br
—H


T449 (a and b)
NH
—H
—F
—H


T450 (a and b)
NH
—H
—CH3
—H


T451 (a and b)
NH
—H
—CF3
—H


T452 (a and b)
NH
—H
—OCH3
—H


T453 (a and b)
NH
—H
—OCH2CH3
—H


T454 (a and b)
NH
—H
—OCF3
—H


T455 (a and b)
NH
—H
-tert-butyl
—H


T456 (a and b)
NH
—H
-iso-propyl
—H


T457 (a and b)
NH
—H
—CH3
—CH3


T458 (a and b)
NH
—H
—H
—H


T459 (a and b)
NH
—H
—H
—Cl


T460 (a and b)
NH
—H
—H
—Br


T461 (a and b)
NH
—H
—H
—F


T462 (a and b)
NH
—H
—H
—CH3


T463 (a and b)
NH
—H
—H
—CF3


T464 (a and b)
NH
—H
—H
—OCH3


T465 (a and b)
NH
—H
—H
—OCH2CH3


T466 (a and b)
NH
—H
—H
—OCF3


T467 (a and b)
NH
—H
—H
-tert-butyl


T468 (a and b)
NH
—H
—H
-iso-propyl


T469 (a and b)
NH
—Cl
—Cl
—H


T470 (a and b)
NH
—Cl
—Br
—H


T471 (a and b)
NH
—Cl
—F
—H


T472 (a and b)
NH
—Cl
—CH3
—H


T473 (a and b)
NH
—Cl
—CF3
—H


T474 (a and b)
NH
—Cl
—OCH3
—H


T475 (a and b)
NH
—Cl
—OCH2CH3
—H


T476 (a and b)
NH
—Cl
—OCF3
—H


T477 (a and b)
NH
—Cl
-tert-butyl
—H


T478 (a and b)
NH
—Cl
-iso-propyl
—H


T479 (a and b)
NH
—Cl
—CH3
—CH3


T480 (a and b)
NH
—Cl
—H
—H


T481 (a and b)
NH
—Cl
—H
—CH3


T482 (a and b)
NH
—Cl
—H
—Cl


T483 (a and b)
NH
—Cl
—H
—Br


T484 (a and b)
NH
—Cl
—H
—F


T485 (a and b)
NH
—Cl
—H
—CF3


T486 (a and b)
NH
—Cl
—H
—OCH3


T487 (a and b)
NH
—Cl
—H
—OCH2CH3


T488 (a and b)
NH
—Cl
—H
—OCF3


T489 (a and b)
NH
—Cl
—H
-tert-butyl


T490 (a and b)
NH
—Cl
—H
-iso-propyl


T491 (a and b)
NH
—Cl
—H
—OCF3


T492 (a and b)
NH
—Cl
—H
-tert-butyl


T493 (a and b)
NH
—Cl
—H
-iso-propyl


T494 (a and b)
NH
—CH3
—Cl
—H


T495 (a and b)
NH
—CH3
—Br
—H


T496 (a and b)
NH
—CH3
—F
—H


T497 (a and b)
NH
—CH3
—CH3
—H


T498 (a and b)
NH
—CH3
—CF3
—H


T499 (a and b)
NH
—CH3
—OCH3
—H


T500 (a and b)
NH
—CH3
—OCH2CH3
—H


T501 (a and b)
NH
—CH3
—OCF3
—H


T502 (a and b)
NH
—CH3
-tert-butyl
—H


T503 (a and b)
NH
—CH3
-iso-propyl
—H


T504 (a and b)
NH
—CH3
—CH3
—CH3


T505 (a and b)
NH
—CH3
—H
—H


T506 (a and b)
NH
—CH3
—H
—Cl


T507 (a and b)
NH
—CH3
—H
—Br


T508 (a and b)
NH
—CH3
—H
—F


T509 (a and b)
NH
—CH3
—H
—CH3


T510 (a and b)
NH
—CH3
—H
—CF3


T511 (a and b)
NH
—CH3
—H
—OCH3


T512 (a and b)
NH
—CH3
—H
—OCH2CH3


T513 (a and b)
NH
—CH3
—H
—OCF3


T514 (a and b)
NH
—CH3
—H
-tert-butyl


T515 (a and b)
NH
—CH3
—H
-iso-propyl


T516 (a and b)
NH
—CF3
—Cl
—H


T517 (a and b)
NH
—CF3
—Br
—H


T518 (a and b)
NH
—CF3
—F
—H


T519 (a and b)
NH
—CF3
—CH3
—H


T520 (a and b)
NH
—CF3
—CF3
—H


T521 (a and b)
NH
—CF3
—OCH3
—H


T522 (a and b)
NH
—CF3
—OCH2CH3
—H


T523 (a and b)
NH
—CF3
—OCF3
—H


T524 (a and b)
NH
—CF3
-tert-butyl
—H


T525 (a and b)
NH
—CF3
-iso-propyl
—H


T526 (a and b)
NH
—CF3
—CH3
—CH3


T527 (a and b)
NH
—CF3
—H
—H


T528 (a and b)
NH
—CF3
—H
—Cl


T529 (a and b)
NH
—CF3
—H
—Br


T530 (a and b)
NH
—CF3
—H
—F


T531 (a and b)
NH
—CF3
—H
—CH3


T532 (a and b)
NH
—CF3
—H
—CF3


T533 (a and b)
NH
—CF3
—H
—OCH3


T534 (a and b)
NH
—CF3
—H
—OCH2CH3


T535 (a and b)
NH
—CF3
—H
—OCF3


T536 (a and b)
NH
—CF3
—H
-tert-butyl


T537 (a and b)
NH
—CF3
—H
-iso-propyl


T538 (a and b)
NH
—CHF2
—Cl
—H


T539 (a and b)
NH
—CHF2
—Br
—H


T540 (a and b)
NH
—CHF2
—F
—H


T541 (a and b)
NH
—CHF2
—CH3
—H


T542 (a and b)
NH
—CHF2
—CF3
—H


T543 (a and b)
NH
—CHF2
—OCH3
—H


T544 (a and b)
NH
—CHF2
—OCH2CH3
—H


T545 (a and b)
NH
—CHF2
—OCF3
—H


T546 (a and b)
NH
—CHF2
-tert-butyl
—H


T547 (a and b)
NH
—CHF2
-iso-propyl
—H


T548 (a and b)
NH
—CHF2
—CH3
—CH3


T549 (a and b)
NH
—CHF2
—H
—H


T550 (a and b)
NH
—CHF2
—H
—Cl


T551 (a and b)
NH
—CHF2
—H
—Br


T552 (a and b)
NH
—CHF2
—H
—F


T553 (a and b)
NH
—CHF2
—H
—CH3


T554 (a and b)
NH
—CHF2
—H
—CF3


T555 (a and b)
NH
—CHF2
—H
—OCH3


T556 (a and b)
NH
—CHF2
—H
—OCH2CH3


T557 (a and b)
NH
—CHF2
—H
—OCF3


T558 (a and b)
NH
—CHF2
—H
-tert-butyl


T559 (a and b)
NH
—CHF2
—H
-iso-propyl


T560 (a and b)
NH
—OH
—Cl
—H


T561 (a and b)
NH
—OH
—Br
—H


T562 (a and b)
NH
—OH
—F
—H


T563 (a and b)
NH
—OH
—CH3
—H


T564 (a and b)
NH
—OH
—CF3
—H


T565 (a and b)
NH
—OH
—OCH3
—H


T566 (a and b)
NH
—OH
—OCH2CH3
—H


T567 (a and b)
NH
—OH
—OCF3
—H


T568 (a and b)
NH
—OH
-tert-butyl
—H


T569 (a and b)
NH
—OH
-iso-propyl
—H


T570 (a and b)
NH
—OH
—CH3
—CH3


T571 (a and b)
NH
—OH
—H
—H


T572 (a and b)
NH
—OH
—H
—Cl


T573 (a and b)
NH
—OH
—H
—Br


T574 (a and b)
NH
—OH
—H
—F


T575 (a and b)
NH
—OH
—H
—CH3


T576 (a and b)
NH
—OH
—H
—CF3


T577 (a and b)
NH
—OH
—H
—OCH3


T578 (a and b)
NH
—OH
—H
—OCH2CH3


T579 (a and b)
NH
—OH
—H
—OCF3


T580 (a and b)
NH
—OH
—H
-tert-butyl


T581 (a and b)
NH
—OH
—H
-iso-propyl


T582 (a and b)
NH
—NO2
—Cl
—H


T583 (a and b)
NH
—NO2
—Br
—H


T584 (a and b)
NH
—NO2
—F
—H


T585 (a and b)
NH
—NO2
—CH3
—H


T586 (a and b)
NH
—NO2
—CF3
—H


T587 (a and b)
NH
—NO2
—OCH3
—H


T588 (a and b)
NH
—NO2
—OCH2CH3
—H


T589 (a and b)
NH
—NO2
—OCF3
—H


T590 (a and b)
NH
—NO2
-tert-butyl
—H


T591 (a and b)
NH
—NO2
-iso-propyl
—H


T592 (a and b)
NH
—NO2
—CH3
—CH3


T593 (a and b)
NH
—NO2
—H
—H


T594 (a and b)
NH
—NO2
—H
—Cl


T595 (a and b)
NH
—NO2
—H
—Br


T596 (a and b)
NH
—NO2
—H
—F


T597 (a and b)
NH
—NO2
—H
—CH3


T598 (a and b)
NH
—NO2
—H
—CF3


T599 (a and b)
NH
—NO2
—H
—OCH3


T600 (a and b)
NH
—NO2
—H
—OCH2CH3


T601 (a and b)
NH
—NO2
—H
—OCF3


T602 (a and b)
NH
—NO2
—H
-tert-butyl


T603 (a and b)
NH
—NO2
—H
-iso-propyl


T604 (a and b)
NH
—CN
—Br
—H


T605 (a and b)
NH
—CN
—Cl
—H


T606 (a and b)
NH
—CN
—F
—H


T607 (a and b)
NH
—CN
—CH3
—H


T608 (a and b)
NH
—CN
—CF3
—H


T609 (a and b)
NH
—CN
—OCH3
—H


T610 (a and b)
NH
—CN
—OCH2CH3
—H


T611 (a and b)
NH
—CN
—OCF3
—H


T612 (a and b)
NH
—CN
-tert-butyl
—H


T613 (a and b)
NH
—CN
-iso-propyl
—H


T614 (a and b)
NH
—CN
—CH3
—CH3


T615 (a and b)
NH
—CN
—H
—H


T616 (a and b)
NH
—CN
—H
—Cl


T617 (a and b)
NH
—CN
—H
—Br


T618 (a and b)
NH
—CN
—H
—F


T619 (a and b)
NH
—CN
—H
—CH3


T620 (a and b)
NH
—CN
—H
—CF3


T621 (a and b)
NH
—CN
—H
—OCH3


T622 (a and b)
NH
—CN
—H
—OCH2CH3


T623 (a and b)
NH
—CN
—H
—OCF3


T624 (a and b)
NH
—CN
—H
-tert-butyl


T625 (a and b)
NH
—CN
—H
-iso-propyl


T626 (a and b)
NH
—Br
—Br
—H


T627 (a and b)
NH
—Br
—Cl
—H


T628 (a and b)
NH
—Br
—F
—H


T629 (a and b)
NH
—Br
—CH3
—H


T630 (a and b)
NH
—Br
—CF3
—H


T631 (a and b)
NH
—Br
—OCH3
—H


T632 (a and b)
NH
—Br
—OCH2CH3
—H


T633 (a and b)
NH
—Br
—OCF3
—H


T634 (a and b)
NH
—Br
-tert-butyl
—H


T635 (a and b)
NH
—Br
-iso-propyl
—H


T636 (a and b)
NH
—Br
—CH3
—CH3


T637 (a and b)
NH
—Br
—H
—H


T638 (a and b)
NH
—Br
—H
—Cl


T639 (a and b)
NH
—Br
—H
—Br


T640 (a and b)
NH
—Br
—H
—F


T641 (a and b)
NH
—Br
—H
—CH3


T642 (a and b)
NH
—Br
—H
—CF3


T643 (a and b)
NH
—Br
—H
—OCH3


T644 (a and b)
NH
—Br
—H
—OCH2CH3


T645 (a and b)
NH
—Br
—H
—OCF3


T646 (a and b)
NH
—Br
—H
-tert-butyl


T647 (a and b)
NH
—Br
—H
-iso-propyl


T648 (a and b)
NH
—I
—Cl
—H


T649 (a and b)
NH
—I
—Br
—H


T650 (a and b)
NH
—I
—F
—H


T651 (a and b)
NH
—I
—CH3
—H


T652 (a and b)
NH
—I
—CF3
—H


T653 (a and b)
NH
—I
—OCH3
—H


T654 (a and b)
NH
—I
—OCH2CH3
—H


T655 (a and b)
NH
—I
—OCF3
—H


T656 (a and b)
NH
—I
-tert-butyl
—H


T657 (a and b)
NH
—I
-iso-propyl
—H


T658 (a and b)
NH
—I
—CH3
—CH3


T659 (a and b)
NH
—I
—H
—H


T660 (a and b)
NH
—I
—H
—Cl


T661 (a and b)
NH
—I
—H
—Br


T662 (a and b)
NH
—I
—H
—F


T663 (a and b)
NH
—I
—H
—CH3


T664 (a and b)
NH
—I
—H
—CF3


T665 (a and b)
NH
—I
—H
—OCH3


T666 (a and b)
NH
—I
—H
—OCH2CH3


T667 (a and b)
NH
—I
—H
—OCF3


T668 (a and b)
NH
—I
—H
-tert-butyl


T669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 21








(Iu)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






U1 (a and b)
—H
—H



U2 (a and b)
—H
-tert-butyl



U3 (a and b)
—H
-iso-butyl



U4 (a and b)
—H
-sec-butyl



U5 (a and b)
—H
-iso-propyl



U6 (a and b)
—H
-n-propyl



U7 (a and b)
—H
-cyclohexyl



U8 (a and b)
—H
-tert-butoxy



U9 (a and b)
—H
-isopropoxy



U10 (a and b)
—H
—CF3



U11 (a and b)
—H
—CH2CF3



U12 (a and b)
—H
—OCF3



U13 (a and b)
—H
—Cl



U14 (a and b)
—H
—Br



U15 (a and b)
—H
—I



U16 (a and b)
—H
-n-butyl



U17 (a and b)
—H
—CH3



U18 (a and b)
—H
—SCF3



U19 (a and b)
—H
—N(CH2CH3)2



U20 (a and b)
—H
—OCF2CHF2



U21 (a and b)
—H
—C(OH)(CF3)2



U22 (a and b)
—H
-(1,1-dimethyl-pentyl)



U23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



U24 (a and b)
—H
—N-piperidinyl



U25 (a and b)
—Cl
—H



U26 (a and b)
—Cl
-tert-butyl



U27 (a and b)
—Cl
-iso-butyl



U28 (a and b)
—Cl
-sec-butyl



U29 (a and b)
—Cl
-iso-propyl



U30 (a and b)
—Cl
-n-propyl



U31 (a and b)
—Cl
-cyclohexyl



U32 (a and b)
—Cl
-tert-butoxy



U33 (a and b)
—Cl
-isopropoxy



U34 (a and b)
—Cl
—CF3



U35 (a and b)
—Cl
—CH2CF3



U36 (a and b)
—Cl
—OCF3



U37 (a and b)
—Cl
—Cl



U38 (a and b)
—Cl
—Br



U39 (a and b)
—Cl
—I



U40 (a and b)
—Cl
-n-butyl



U41 (a and b)
—Cl
—CH3



U42 (a and b)
—Cl
—SCF3



U43 (a and b)
—Cl
—N(CH2CH3)2



U44 (a and b)
—Cl
—OCF2CHF2



U45 (a and b)
—Cl
—C(OH)(CF3)2



U46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



U47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



U48 (a and b)
—Cl
—N-piperidinyl



U49 (a and b)
—F
—H



U50 (a and b)
—F
-tert-butyl



U51 (a and b)
—F
-iso-butyl



U52 (a and b)
—F
-sec-butyl



U53 (a and b)
—F
-iso-propyl



U54 (a and b)
—F
-n-propyl



U55 (a and b)
—F
-cyclohexyl



U56 (a and b)
—F
-tert-butoxy



U57 (a and b)
—F
-isopropoxy



U58 (a and b)
—F
—CF3



U59 (a and b)
—F
—CH2CF3



U60 (a and b)
—F
—OCF3



U61 (a and b)
—F
—Cl



U62 (a and b)
—F
—Br



U63 (a and b)
—F
—I



U64 (a and b)
—F
-n-butyl



U65 (a and b)
—F
—CH3



U66 (a and b)
—F
—SCF3



U67 (a and b)
—F
—N(CH2CH3)2



U68 (a and b)
—F
—OCF2CHF2



U69 (a and b)
—F
—C(OH)(CF3)2



U70 (a and b)
—F
-(1,1-dimethyl-pentyl)



U71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



U72 (a and b)
—F
—N-piperidinyl



U73 (a and b)
—CH3
—H



U74 (a and b)
—CH3
-iso-butyl



U75 (a and b)
—CH3
-tert-butyl



U76 (a and b)
—CH3
-sec-butyl



U77 (a and b)
—CH3
-iso-propyl



U78 (a and b)
—CH3
-n-propyl



U79 (a and b)
—CH3
-cyclohexyl



U80 (a and b)
—CH3
-tert-butoxy



U81 (a and b)
—CH3
-isopropoxy



U82 (a and b)
—CH3
—CF3



U83 (a and b)
—CH3
—CH2CF3



U84 (a and b)
—CH3
—OCF3



U85 (a and b)
—CH3
—Cl



U86 (a and b)
—CH3
—Br



U87 (a and b)
—CH3
—I



U88 (a and b)
—CH3
-n-butyl



U89 (a and b)
—CH3
—CH3



U90 (a and b)
—CH3
—SCF3



U91 (a and b)
—CH3
—N(CH2CH3)2



U92 (a and b)
—CH3
—OCF2CHF2



U93 (a and b)
—CH3
—C(OH)(CF3)2



U94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



U95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



U96 (a and b)
—CH3
—N-piperidinyl



U97 (a and b)
—CF3
—H



U98 (a and b)
—CF3
-tert-butyl



U99 (a and b)
—CF3
-iso-butyl



U100 (a and b)
—CF3
-sec-butyl



U101 (a and b)
—CF3
-iso-propyl



U102 (a and b)
—CF3
-n-propyl



U103 (a and b)
—CF3
-cyclohexyl



U104 (a and b)
—CF3
-tert-butoxy



U105 (a and b)
—CF3
-isopropoxy



U106 (a and b)
—CF3
—CF3



U107 (a and b)
—CF3
—CH2CF3



U108 (a and b)
—CF3
—OCF3



U109 (a and b)
—CF3
—Cl



U110 (a and b)
—CF3
—Br



U111 (a and b)
—CF3
—I



U112 (a and b)
—CF3
-n-butyl



U113 (a and b)
—CF3
—CH3



U114 (a and b)
—CF3
—SCF3



U115 (a and b)
—CF3
—N(CH2CH3)2



U116 (a and b)
—CF3
—OCF2CHF2



U117 (a and b)
—CF3
—C(OH)(CF3)2



U118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



U119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



U120 (a and b)
—CF3
—N-piperidinyl



U121 (a and b)
—CHF2
-tert-butyl



U122 (a and b)
—CHF2
—H



U123 (a and b)
—CHF2
-iso-butyl



U124 (a and b)
—CHF2
-sec-butyl



U125 (a and b)
—CHF2
-iso-propyl



U126 (a and b)
—CHF2
-n-propyl



U127 (a and b)
—CHF2
-cyclohexyl



U128 (a and b)
—CHF2
-tert-butoxy



U129 (a and b)
—CHF2
-isopropoxy



U130 (a and b)
—CHF2
—CF3



U131 (a and b)
—CHF2
—CH2CF3



U132 (a and b)
—CHF2
—OCF3



U133 (a and b)
—CHF2
—Cl



U134 (a and b)
—CHF2
—Br



U135 (a and b)
—CHF2
—I



U136 (a and b)
—CHF2
-n-butyl



U137 (a and b)
—CHF2
—CH3



U138 (a and b)
—CHF2
—SCF3



U139 (a and b)
—CHF2
—N(CH2CH3)2



U140 (a and b)
—CHF2
—OCF2CHF2



U141 (a and b)
—CHF2
—C(OH)(CF3)2



U142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



U143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



U144 (a and b)
—CHF2
—N-piperidinyl



U145 (a and b)
—OH
—H



U146 (a and b)
—OH
-tert-butyl



U147 (a and b)
—OH
-iso-butyl



U148 (a and b)
—OH
-sec-butyl



U149 (a and b)
—OH
-iso-propyl



U150 (a and b)
—OH
-n-propyl



U151 (a and b)
—OH
-cyclohexyl



U152 (a and b)
—OH
-tert-butoxy



U153 (a and b)
—OH
-isopropoxy



U154 (a and b)
—OH
—CF3



U155 (a and b)
—OH
—CH2CF3



U156 (a and b)
—OH
—OCF3



U157 (a and b)
—OH
—Cl



U158 (a and b)
—OH
—Br



U159 (a and b)
—OH
—I



U160 (a and b)
—OH
-n-butyl



U161 (a and b)
—OH
—CH3



U162 (a and b)
—OH
—SCF3



U163 (a and b)
—OH
—N(CH2CH3)2



U164 (a and b)
—OH
—OCF2CHF2



U165 (a and b)
—OH
—C(OH)(CF3)2



U166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



U167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



U168 (a and b)
—OH
—N-piperidinyl



U169 (a and b)
—NO2
—H



U170 (a and b)
—NO2
-tert-butyl



U171 (a and b)
—NO2
-iso-butyl



U172 (a and b)
—NO2
-sec-butyl



U173 (a and b)
—NO2
-iso-propyl



U174 (a and b)
—NO2
-n-propyl



U175 (a and b)
—NO2
-cyclohexyl



U176 (a and b)
—NO2
-tert-butoxy



U177 (a and b)
—NO2
-isopropoxy



U178 (a and b)
—NO2
—CF3



U179 (a and b)
—NO2
—CH2CF3



U180 (a and b)
—NO2
—OCF3



U181 (a and b)
—NO2
—Cl



U182 (a and b)
—NO2
—Br



U183 (a and b)
—NO2
—I



U184 (a and b)
—NO2
-n-butyl



U185 (a and b)
—NO2
—CH3



U186 (a and b)
—NO2
—SCF3



U187 (a and b)
—NO2
—N(CH2CH3)2



U188 (a and b)
—NO2
—OCF2CHF2



U189 (a and b)
—NO2
—C(OH)(CF3)2



U190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



U191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



U192 (a and b)
—NO2
—N-piperidinyl



U193 (a and b)
—CN
—H



U194 (a and b)
—CN
-tert-butyl



U195 (a and b)
—CN
-iso-butyl



U196 (a and b)
—CN
-sec-butyl



U197 (a and b)
—CN
-iso -propyl



U198 (a and b)
—CN
-n-propyl



U199 (a and b)
—CN
-cyclohexyl



U200 (a and b)
—CN
-tert-butoxy



U201 (a and b)
—CN
-isopropoxy



U202 (a and b)
—CN
—CF3



U203 (a and b)
—CN
—CH2CF3



U204 (a and b)
—CN
—OCF3



U205 (a and b)
—CN
—Cl



U206 (a and b)
—CN
—Br



U207 (a and b)
—CN
—I



U208 (a and b)
—CN
-n-butyl



U209 (a and b)
—CN
—CH3



U210 (a and b)
—CN
—SCF3



U211 (a and b)
—CN
—N(CH2CH3)2



U212 (a and b)
—CN
—OCF2CHF2



U213 (a and b)
—CN
—C(OH)(CF3)2



U214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



U215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



U216 (a and b)
—CN
—N-piperidinyl



U217 (a and b)
—Br
—H



U218 (a and b)
—Br
-tert-butyl



U219 (a and b)
—Br
-iso-butyl



U220 (a and b)
—Br
-sec-butyl



U221 (a and b)
—Br
-iso-propyl



U222 (a and b)
—Br
-n-propyl



U223 (a and b)
—Br
-cyclohexyl



U224 (a and b)
—Br
-tert-butoxy



U225 (a and b)
—Br
-isopropoxy



U226 (a and b)
—Br
—CF3



U227 (a and b)
—Br
—CH2CF3



U228 (a and b)
—Br
—OCF3



U229 (a and b)
—Br
—Cl



U230 (a and b)
—Br
—Br



U231 (a and b)
—Br
—I



U232 (a and b)
—Br
-n-butyl



U233 (a and b)
—Br
—CH3



U234 (a and b)
—Br
—SCF3



U235 (a and b)
—Br
—N(CH2CH3)2



U236 (a and b)
—Br
—OCF2CHF2



U237 (a and b)
—Br
—C(OH)(CF3)2



U238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



U239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



U240 (a and b)
—Br
—N-piperidinyl



U241 (a and b)
—I
-tert-butyl



U242 (a and b)
—I
—H



U243 (a and b)
—I
-iso-butyl



U244 (a and b)
—I
-sec-butyl



U245 (a and b)
—I
-iso-propyl



U246 (a and b)
—I
-n-propyl



U247 (a and b)
—I
-cyclohexyl



U248 (a and b)
—I
-tert-butoxy



U249 (a and b)
—I
-isopropoxy



U250 (a and b)
—I
—CF3



U251 (a and b)
—I
—CH2CF3



U252 (a and b)
—I
—OCF3



U253 (a and b)
—I
—Cl



U254 (a and b)
—I
—Br



U255 (a and b)
—I
—I



U256 (a and b)
—I
-n-butyl



U257 (a and b)
—I
—CH3



U258 (a and b)
—I
—SCF3



U259 (a and b)
—I
—N(CH2CH3)2



U260 (a and b)
—I
—OCF2CHF2



U261 (a and b)
—I
—C(OH)(CF3)2



U262 (a and b)
—I
-(1,1-dimethyl-pentyl)



U263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



U264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 22








(Iv)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
R1
R8a






V1 (a and b)
—H
—H



V2 (a and b)
—H
-tert-butyl



V3 (a and b)
—H
-iso-butyl



V4 (a and b)
—H
-sec-butyl



V5 (a and b)
—H
-iso-propyl



V6 (a and b)
—H
-n-propyl



V7 (a and b)
—H
-cyclohexyl



V8 (a and b)
—H
-tert-butoxy



V9 (a and b)
—H
-isopropoxy



V10 (a and b)
—H
—CF3



V11 (a and b)
—H
—CH2CF3



V12 (a and b)
—H
—OCF3



V13 (a and b)
—H
—Cl



V14 (a and b)
—H
—Br



V15 (a and b)
—H
—I



V16 (a and b)
—H
-n-butyl



V17 (a and b)
—H
—CH3



V18 (a and b)
—H
—SCF3



V19 (a and b)
—H
—N(CH2CH3)2



V20 (a and b)
—H
—OCF2CHF2



V21 (a and b)
—H
—C(OH)(CF3)2



V22 (a and b)
—H
-(1,1-dimethyl-pentyl)



V23 (a and b)
—H
-(1,1-dimethyl-acetic





acid) ethyl ester



V24 (a and b)
—H
—N-piperidinyl



V25 (a and b)
—Cl
—H



V26 (a and b)
—Cl
-tert-butyl



V27 (a and b)
—Cl
-iso-butyl



V28 (a and b)
—Cl
-sec-butyl



V29 (a and b)
—Cl
-iso-propyl



V30 (a and b)
—Cl
-n-propyl



V31 (a and b)
—Cl
-cyclohexyl



V32 (a and b)
—Cl
-tert-butoxy



V33 (a and b)
—Cl
-isopropoxy



V34 (a and b)
—Cl
—CF3



V35 (a and b)
—Cl
—CH2CF3



V36 (a and b)
—Cl
—OCF3



V37 (a and b)
—Cl
—Cl



V38 (a and b)
—Cl
—Br



V39 (a and b)
—Cl
—I



V40 (a and b)
—Cl
-n-butyl



V41 (a and b)
—Cl
—CH3



V42 (a and b)
—Cl
—SCF3



V43 (a and b)
—Cl
—N(CH2CH3)2



V44 (a and b)
—Cl
—OCF2CHF2



V45 (a and b)
—Cl
—C(OH)(CF3)2



V46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)



V47 (a and b)
—Cl
-(1,1-dimethyl-acetic





acid) ethyl ester



V48 (a and b)
—Cl
—N-piperidinyl



V49 (a and b)
—F
—H



V50 (a and b)
—F
-tert-butyl



V51 (a and b)
—F
-iso-butyl



V52 (a and b)
—F
-sec-butyl



V53 (a and b)
—F
-iso-propyl



V54 (a and b)
—F
-n-propyl



V55 (a and b)
—F
-cyclohexyl



V56 (a and b)
—F
-tert-butoxy



V57 (a and b)
—F
-isopropoxy



V58 (a and b)
—F
—CF3



V59 (a and b)
—F
—CH2CF3



V60 (a and b)
—F
—OCF3



V61 (a and b)
—F
—Cl



V62 (a and b)
—F
—Br



V63 (a and b)
—F
—I



V64 (a and b)
—F
-n-butyl



V65 (a and b)
—F
—CH3



V66 (a and b)
—F
—SCF3



V67 (a and b)
—F
—N(CH2CH3)2



V68 (a and b)
—F
—OCF2CHF2



V69 (a and b)
—F
—C(OH)(CF3)2



V70 (a and b)
—F
-(1,1-dimethyl-pentyl)



V71 (a and b)
—F
-(1,1-dimethyl-acetic





acid) ethyl ester



V72 (a and b)
—F
—N-piperidinyl



V73 (a and b)
—CH3
—H



V74 (a and b)
—CH3
-iso-butyl



V75 (a and b)
—CH3
-tert-butyl



V76 (a and b)
—CH3
-sec-butyl



V77 (a and b)
—CH3
-iso-propyl



V78 (a and b)
—CH3
-n-propyl



V79 (a and b)
—CH3
-cyclohexyl



V80 (a and b)
—CH3
-tert-butoxy



V81 (a and b)
—CH3
-isopropoxy



V82 (a and b)
—CH3
—CF3



V83 (a and b)
—CH3
—CH2CF3



V84 (a and b)
—CH3
—OCF3



V85 (a and b)
—CH3
—Cl



V86 (a and b)
—CH3
—Br



V87 (a and b)
—CH3
—I



V88 (a and b)
—CH3
-n-butyl



V89 (a and b)
—CH3
—CH3



V90 (a and b)
—CH3
—SCF3



V91 (a and b)
—CH3
—N(CH2CH3)2



V92 (a and b)
—CH3
—OCF2CHF2



V93 (a and b)
—CH3
—C(OH)(CF3)2



V94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)



V95 (a and b)
—CH3
-(1,1-dimethyl-acetic





acid) ethyl ester



V96 (a and b)
—CH3
—N-piperidinyl



V97 (a and b)
—CF3
—H



V98 (a and b)
—CF3
-tert-butyl



V99 (a and b)
—CF3
-iso-butyl



V100 (a and b)
—CF3
-sec-butyl



V101 (a and b)
—CF3
-iso-propyl



V102 (a and b)
—CF3
-n-propyl



V103 (a and b)
—CF3
-cyclohexyl



V104 (a and b)
—CF3
-tert-butoxy



V105 (a and b)
—CF3
-isopropoxy



V106 (a and b)
—CF3
—CF3



V107 (a and b)
—CF3
—CH2CF3



V108 (a and b)
—CF3
—OCF3



V109 (a and b)
—CF3
—Cl



V110 (a and b)
—CF3
—Br



V111 (a and b)
—CF3
—I



V112 (a and b)
—CF3
-n-butyl



V113 (a and b)
—CF3
—CH3



V114 (a and b)
—CF3
—SCF3



V115 (a and b)
—CF3
—N(CH2CH3)2



V116 (a and b)
—CF3
—OCF2CHF2



V117 (a and b)
—CF3
—C(OH)(CF3)2



V118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)



V119 (a and b)
—CF3
-(1,1-dimethyl-acetic





acid) ethyl ester



V120 (a and b)
—CF3
—N-piperidinyl



V121 (a and b)
—CHF2
-tert-butyl



V122 (a and b)
—CHF2
—H



V123 (a and b)
—CHF2
-iso-butyl



V124 (a and b)
—CHF2
-sec-butyl



V125 (a and b)
—CHF2
-iso-propyl



V126 (a and b)
—CHF2
-n-propyl



V127 (a and b)
—CHF2
-cyclohexyl



V128 (a and b)
—CHF2
-tert-butoxy



V129 (a and b)
—CHF2
-isopropoxy



V130 (a and b)
—CHF2
—CF3



V131 (a and b)
—CHF2
—CH2CF3



V132 (a and b)
—CHF2
—OCF3



V133 (a and b)
—CHF2
—Cl



V134 (a and b)
—CHF2
—Br



V135 (a and b)
—CHF2
—I



V136 (a and b)
—CHF2
-n-butyl



V137 (a and b)
—CHF2
—CH3



V138 (a and b)
—CHF2
—SCF3



V139 (a and b)
—CHF2
—N(CH2CH3)2



V140 (a and b)
—CHF2
—OCF2CHF2



V141 (a and b)
—CHF2
—C(OH)(CF3)2



V142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)



V143 (a and b)
—CHF2
-(1,1-dimethyl-acetic





acid) ethyl ester



V144 (a and b)
—CHF2
—N-piperidinyl



V145 (a and b)
—OH
—H



V146 (a and b)
—OH
-tert-butyl



V147 (a and b)
—OH
-iso-butyl



V148 (a and b)
—OH
-sec-butyl



V149 (a and b)
—OH
-iso-propyl



V150 (a and b)
—OH
-n-propyl



V151 (a and b)
—OH
-cyclohexyl



V152 (a and b)
—OH
-tert-butoxy



V153 (a and b)
—OH
-isopropoxy



V154 (a and b)
—OH
—CF3



V155 (a and b)
—OH
—CH2CF3



V156 (a and b)
—OH
—OCF3



V157 (a and b)
—OH
—Cl



V158 (a and b)
—OH
—Br



V159 (a and b)
—OH
—I



V160 (a and b)
—OH
-n-butyl



V161 (a and b)
—OH
—CH3



V162 (a and b)
—OH
—SCF3



V163 (a and b)
—OH
—N(CH2CH3)2



V164 (a and b)
—OH
—OCF2CHF2



V165 (a and b)
—OH
—C(OH)(CF3)2



V166 (a and b)
—OH
-(1,1-dimethyl-pentyl)



V167 (a and b)
—OH
-(1,1-dimethyl-acetic





acid) ethyl ester



V168 (a and b)
—OH
—N-piperidinyl



V169 (a and b)
—NO2
—H



V170 (a and b)
—NO2
-tert-butyl



V171 (a and b)
—NO2
-iso-butyl



V172 (a and b)
—NO2
-sec-butyl



V173 (a and b)
—NO2
-iso-propyl



V174 (a and b)
—NO2
-n-propyl



V175 (a and b)
—NO2
-cyclohexyl



V176 (a and b)
—NO2
-tert-butoxy



V177 (a and b)
—NO2
-isopropoxy



V178 (a and b)
—NO2
—CF3



V179 (a and b)
—NO2
—CH2CF3



V180 (a and b)
—NO2
—OCF3



V181 (a and b)
—NO2
—Cl



V182 (a and b)
—NO2
—Br



V183 (a and b)
—NO2
—I



V184 (a and b)
—NO2
-n-butyl



V185 (a and b)
—NO2
—CH3



V186 (a and b)
—NO2
—SCF3



V187 (a and b)
—NO2
—N(CH2CH3)2



V188 (a and b)
—NO2
—OCF2CHF2



V189 (a and b)
—NO2
—C(OH)(CF3)2



V190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)



V191 (a and b)
—NO2
-(1,1-dimethyl-acetic





acid) ethyl ester



V192 (a and b)
—NO2
—N-piperidinyl



V193 (a and b)
—CN
—H



V194 (a and b)
—CN
-tert-butyl



V195 (a and b)
—CN
-iso-butyl



V196 (a and b)
—CN
-sec-butyl



V197 (a and b)
—CN
-iso-propyl



V198 (a and b)
—CN
-n-propyl



V199 (a and b)
—CN
-cyclohexyl



V200 (a and b)
—CN
-tert-butoxy



V201 (a and b)
—CN
-isopropoxy



V202 (a and b)
—CN
—CF3



V203 (a and b)
—CN
—CH2CF3



V204 (a and b)
—CN
—OCF3



V205 (a and b)
—CN
—Cl



V206 (a and b)
—CN
—Br



V207 (a and b)
—CN
—I



V208 (a and b)
—CN
-n-butyl



V209 (a and b)
—CN
—CH3



V210 (a and b)
—CN
—SCF3



V211 (a and b)
—CN
—N(CH2CH3)2



V212 (a and b)
—CN
—OCF2CHF2



V213 (a and b)
—CN
—C(OH)(CF3)2



V214 (a and b)
—CN
-(1,1-dimethyl-pentyl)



V215 (a and b)
—CN
-(1,1-dimethyl-acetic





acid) ethyl ester



V216 (a and b)
—CN
—N-piperidinyl



V217 (a and b)
—Br
—H



V218 (a and b)
—Br
-tert-butyl



V219 (a and b)
—Br
-iso-butyl



V220 (a and b)
—Br
-sec-butyl



V221 (a and b)
—Br
-iso-propyl



V222 (a and b)
—Br
-n-propyl



V223 (a and b)
—Br
-cyclohexyl



V224 (a and b)
—Br
-tert-butoxy



V225 (a and b)
—Br
-isopropoxy



V226 (a and b)
—Br
—CF3



V227 (a and b)
—Br
—CH2CF3



V228 (a and b)
—Br
—OCF3



V229 (a and b)
—Br
—Cl



V230 (a and b)
—Br
—Br



V231 (a and b)
—Br
—I



V232 (a and b)
—Br
-n-butyl



V233 (a and b)
—Br
—CH3



V234 (a and b)
—Br
—SCF3



V235 (a and b)
—Br
—N(CH2CH3)2



V236 (a and b)
—Br
—OCF2CHF2



V237 (a and b)
—Br
—C(OH)(CF3)2



V238 (a and b)
—Br
-(1,1-dimethyl-pentyl)



V239 (a and b)
—Br
-(1,1-dimethyl-acetic





acid) ethyl ester



V240 (a and b)
—Br
—N-piperidinyl



V241 (a and b)
—I
-tert-butyl



V242 (a and b)
—I
—H



V243 (a and b)
—I
-iso-butyl



V244 (a and b)
—I
-sec-butyl



V245 (a and b)
—I
-iso-propyl



V246 (a and b)
—I
-n-propyl



V247 (a and b)
—I
-cyclohexyl



V248 (a and b)
—I
-tert-butoxy



V249 (a and b)
—I
-isopropoxy



V250 (a and b)
—I
—CF3



V251 (a and b)
—I
—CH2CF3



V252 (a and b)
—I
—OCF3



V253 (a and b)
—I
—Cl



V254 (a and b)
—I
—Br



V255 (a and b)
—I
—I



V256 (a and b)
—I
-n-butyl



V257 (a and b)
—I
—CH3



V258 (a and b)
—I
—SCF3



V259 (a and b)
—I
—N(CH2CH3)2



V260 (a and b)
—I
—OCF2CHF2



V261 (a and b)
—I
—C(OH)(CF3)2



V262 (a and b)
—I
-(1,1-dimethyl-pentyl)



V263 (a and b)
—I
-(1,1-dimethyl-acetic





acid) ethyl ester



V264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 23








(Iw)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
Y
R1
(R8)a
(R8)b





W1 (a and b)
S
—H
—Cl
—H


W2 (a and b)
S
—H
—Br
—H


W3 (a and b)
S
—H
—F
—H


W4 (a and b)
S
—H
—CH3
—H


W5 (a and b)
S
—H
—CF3
—H


W6 (a and b)
S
—H
—OCH3
—H


W7 (a and b)
S
—H
—OCH2CH3
—H


W8 (a and b)
S
—H
—OCF3
—H


W9 (a and b)
S
—H
-tert-butyl
—H


W10 (a and b)
S
—H
-iso-propyl
—H


W11 (a and b)
S
—H
—CH3
—CH3


W12 (a and b)
S
—H
—H
—H


W13 (a and b)
S
—H
—H
—Cl


W14 (a and b)
S
—H
—H
—Br


W15 (a and b)
S
—H
—H
—F


W16 (a and b)
S
—H
—H
—CH3


W17 (a and b)
S
—H
—H
—CF3


W18 (a and b)
S
—H
—H
—OCH3


W19 (a and b)
S
—H
—H
—OCH2CH3


W20 (a and b)
S
—H
—H
—OCF3


W21 (a and b)
S
—H
—H
-tert-butyl


W22 (a and b)
S
—H
—H
-iso-propyl


W23 (a and b)
S
—Cl
—Cl
—H


W24 (a and b)
S
—Cl
—Br
—H


W25 (a and b)
S
—Cl
—F
—H


W26 (a and b)
S
—Cl
—CH3
—H


W27 (a and b)
S
—Cl
—CF3
—H


W28 (a and b)
S
—Cl
—OCH3
—H


W29 (a and b)
S
—Cl
—OCH2CH3
—H


W30 (a and b)
S
—Cl
—OCF3
—H


W31 (a and b)
S
—Cl
-tert-butyl
—H


W32 (a and b)
S
—Cl
-iso-propyl
—H


W33 (a and b)
S
—Cl
—CH3
—CH3


W34 (a and b)
S
—Cl
—H
—H


W35 (a and b)
S
—Cl
—H
—Cl


W36 (a and b)
S
—Cl
—H
—Br


W37 (a and b)
S
—Cl
—H
—F


W38 (a and b)
S
—Cl
—H
—CH3


W39 (a and b)
S
—Cl
—H
—CF3


W40 (a and b)
S
—Cl
—H
—OCH3


W41 (a and b)
S
—Cl
—H
—OCH2CH3


W42 (a and b)
S
—Cl
—H
—OCF3


W43 (a and b)
S
—Cl
—H
-tert-butyl


W44 (a and b)
S
—Cl
—H
-iso-propyl


W45 (a and b)
S
—Cl
—H
—OCF3


W46 (a and b)
S
—Cl
—H
-tert-butyl


W47 (a and b)
S
—Cl
—H
-iso-propyl


W48 (a and b)
S
—CH3
—Cl
—H


W49 (a and b)
S
—CH3
—Br
—H


W50 (a and b)
S
—CH3
—F
—H


W51 (a and b)
S
—CH3
—CH3
—H


W52 (a and b)
S
—CH3
—CF3
—H


W53 (a and b)
S
—CH3
—OCH3
—H


W54 (a and b)
S
—CH3
—OCH2CH3
—H


W55 (a and b)
S
—CH3
—OCF3
—H


W56 (a and b)
S
—CH3
-tert-butyl
—H


W57 (a and b)
S
—CH3
-iso-propyl
—H


W58 (a and b)
S
—CH3
—CH3
—CH3


W59 (a and b)
S
—CH3
—H
—H


W60 (a and b)
S
—CH3
—H
—Cl


W61 (a and b)
S
—CH3
—H
—Br


W62 (a and b)
S
—CH3
—H
—F


W63 (a and b)
S
—CH3
—H
—CH3


W64 (a and b)
S
—CH3
—H
—CF3


W65 (a and b)
S
—CH3
—H
—OCH3


W66 (a and b)
S
—CH3
—H
—OCH2CH3


W67 (a and b)
S
—CH3
—H
—OCF3


W68 (a and b)
S
—CH3
—H
-tert-butyl


W69 (a and b)
S
—CH3
—H
-iso-propyl


W70 (a and b)
S
—CF3
—Cl
—H


W71 (a and b)
S
—CF3
—Br
—H


W72 (a and b)
S
—CF3
—F
—H


W73 (a and b)
S
—CF3
—CH3
—H


W74 (a and b)
S
—CF3
—CF3
—H


W75 (a and b)
S
—CF3
—OCH3
—H


W76 (a and b)
S
—CF3
—OCH2CH3
—H


W77 (a and b)
S
—CF3
—OCF3
—H


W78 (a and b)
S
—CF3
-tert-butyl
—H


W79 (a and b)
S
—CF3
-iso-propyl
—H


W80 (a and b)
S
—CF3
—CH3
—CH3


W81 (a and b)
S
—CF3
—H
—H


W82 (a and b)
S
—CF3
—H
—Cl


W83 (a and b)
S
—CF3
—H
—Br


W84 (a and b)
S
—CF3
—H
—F


W85 (a and b)
S
—CF3
—H
—CH3


W86 (a and b)
S
—CF3
—H
—CF3


W87 (a and b)
S
—CF3
—H
—OCH3


W88 (a and b)
S
—CF3
—H
—OCH2CH3


W89 (a and b)
S
—CF3
—H
—OCF3


W90 (a and b)
S
—CF3
—H
-tert-butyl


W91 (a and b)
S
—CF3
—H
-iso-propyl


W92 (a and b)
S
—CHF2
—Cl
—H


W93 (a and b)
S
—CHF2
—Br
—H


W94 (a and b)
S
—CHF2
—F
—H


W95 (a and b)
S
—CHF2
—CH3
—H


W96 (a and b)
S
—CHF2
—CF3
—H


W97 (a and b)
S
—CHF2
—OCH3
—H


W98 (a and b)
S
—CHF2
—OCH2CH3
—H


W99 (a and b)
S
—CHF2
—OCF3
—H


W100 (a and b)
S
—CHF2
-tert-butyl
—H


W101 (a and b)
S
—CHF2
-iso-propyl
—H


W102 (a and b)
S
—CHF2
—CH3
—CH3


W103 (a and b)
S
—CHF2
—H
—H


W104 (a and b)
S
—CHF2
—H
—Cl


W105 (a and b)
S
—CHF2
—H
—Br


W106 (a and b)
S
—CHF2
—H
—F


W107 (a and b)
S
—CHF2
—H
—CH3


W108 (a and b)
S
—CHF2
—H
—CF3


W109 (a and b)
S
—CHF2
—H
—OCH3


W110 (a and b)
S
—CHF2
—H
—OCH2CH3


W111 (a and b)
S
—CHF2
—H
—OCF3


W112 (a and b)
S
—CHF2
—H
-tert-butyl


W113 (a and b)
S
—CHF2
—H
-iso-propyl


W114 (a and b)
S
—OH
—Cl
—H


W115 (a and b)
S
—OH
—Br
—H


W116 (a and b)
S
—OH
—F
—H


W117 (a and b)
S
—OH
—CH3
—H


W118 (a and b)
S
—OH
—CF3
—H


W119 (a and b)
S
—OH
—OCH3
—H


W120 (a and b)
S
—OH
—OCH2CH3
—H


W121 (a and b)
S
—OH
—OCF3
—H


W122 (a and b)
S
—OH
-tert-butyl
—H


W123 (a and b)
S
—OH
-iso-propyl
—H


W124 (a and b)
S
—OH
—CH3
—CH3


W125 (a and b)
S
—OH
—H
—H


W126 (a and b)
S
—OH
—H
—Cl


W127 (a and b)
S
—OH
—H
—Br


W128 (a and b)
S
—OH
—H
—F


W129 (a and b)
S
—OH
—H
—CH3


W130 (a and b)
S
—OH
—H
—CF3


W131 (a and b)
S
—OH
—H
—OCH3


W132 (a and b)
S
—OH
—H
—OCH2CH3


W133 (a and b)
S
—OH
—H
—OCF3


W134 (a and b)
S
—OH
—H
-tert-butyl


W135 (a and b)
S
—OH
—H
-iso-propyl


W136 (a and b)
S
—NO2
—Cl
—H


W137 (a and b)
S
—NO2
—Br
—H


W138 (a and b)
S
—NO2
—F
—H


W139 (a and b)
S
—NO2
—CH3
—H


W140 (a and b)
S
—NO2
—CF3
—H


W141 (a and b)
S
—NO2
—OCH3
—H


W142 (a and b)
S
—NO2
—OCH2CH3
—H


W143 (a and b)
S
—NO2
—OCF3
—H


W144 (a and b)
S
—NO2
-tert-butyl
—H


W145 (a and b)
S
—NO2
-iso-propyl
—H


W146 (a and b)
S
—NO2
—CH3
—CH3


W147 (a and b)
S
—NO2
—H
—H


W148 (a and b)
S
—NO2
—H
—Cl


W149 (a and b)
S
—NO2
—H
—Br


W150 (a and b)
S
—NO2
—H
—F


W151 (a and b)
S
—NO2
—H
—CH3


W152 (a and b)
S
—NO2
—H
—CF3


W153 (a and b)
S
—NO2
—H
—OCH3


W154 (a and b)
S
—NO2
—H
—OCH2CH3


W155 (a and b)
S
—NO2
—H
—OCF3


W156 (a and b)
S
—NO2
—H
-tert-butyl


W157 (a and b)
S
—NO2
—H
-iso-propyl


W158 (a and b)
S
—CN
—Br
—H


W159 (a and b)
S
—CN
—Cl
—H


W160 (a and b)
S
—CN
—F
—H


W161 (a and b)
S
—CN
—CH3
—H


W162 (a and b)
S
—CN
—CF3
—H


W163 (a and b)
S
—CN
—OCH3
—H


W164 (a and b)
S
—CN
—OCH2CH3
—H


W165 (a and b)
S
—CN
—OCF3
—H


W166 (a and b)
S
—CN
-tert-butyl
—H


W167 (a and b)
S
—CN
-iso-propyl
—H


W168 (a and b)
S
—CN
—CH3
—CH3


W169 (a and b)
S
—CN
—H
—H


W170 (a and b)
S
—CN
—H
—Cl


W171 (a and b)
S
—CN
—H
—Br


W172 (a and b)
S
—CN
—H
—F


W173 (a and b)
S
—CN
—H
—CH3


W174 (a and b)
S
—CN
—H
—CF3


W175 (a and b)
S
—CN
—H
—OCH3


W176 (a and b)
S
—CN
—H
—OCH2CH3


W177 (a and b)
S
—CN
—H
—OCF3


W178 (a and b)
S
—CN
—H
-tert-butyl


W179 (a and b)
S
—CN
—H
-iso-propyl


W180 (a and b)
S
—Br
—Br
—H


W181 (a and b)
S
—Br
—Cl
—H


W182 (a and b)
S
—Br
—F
—H


W183 (a and b)
S
—Br
—CH3
—H


W184 (a and b)
S
—Br
—CF3
—H


W185 (a and b)
S
—Br
—OCH3
—H


W186 (a and b)
S
—Br
—OCH2CH3
—H


W187 (a and b)
S
—Br
—OCF3
—H


W188 (a and b)
S
—Br
-tert-butyl
—H


W189 (a and b)
S
—Br
-iso-propyl
—H


W190 (a and b)
S
—Br
—CH3
—CH3


W191 (a and b)
S
—Br
—H
—H


W192 (a and b)
S
—Br
—H
—Cl


W193 (a and b)
S
—Br
—H
—Br


W194 (a and b)
S
—Br
—H
—F


W195 (a and b)
S
—Br
—H
—CH3


W196 (a and b)
S
—Br
—H
—CF3


W197 (a and b)
S
—Br
—H
—OCH3


W198 (a and b)
S
—Br
—H
—OCH2CH3


W199 (a and b)
S
—Br
—H
—OCF3


W200 (a and b)
S
—Br
—H
-tert-butyl


W201 (a and b)
S
—Br
—H
-iso-propyl


W202 (a and b)
S
—I
—Cl
—H


W203 (a and b)
S
—I
—Br
—H


W204 (a and b)
S
—I
—F
—H


W205 (a and b)
S
—I
—CH3
—H


W206 (a and b)
S
—I
—CF3
—H


W207 (a and b)
S
—I
—OCH3
—H


W208 (a and b)
S
—I
—OCH2CH3
—H


W209 (a and b)
S
—I
—OCF3
—H


W210 (a and b)
S
—I
-tert-butyl
—H


W211 (a and b)
S
—I
-iso-propyl
—H


W212 (a and b)
S
—I
—CH3
—CH3


W213 (a and b)
S
—I
—H
—H


W214 (a and b)
S
—I
—H
—Cl


W215 (a and b)
S
—I
—H
—Br


W216 (a and b)
S
—I
—H
—F


W217 (a and b)
S
—I
—H
—CH3


W218 (a and b)
S
—I
—H
—CF3


W219 (a and b)
S
—I
—H
—OCH3


W220 (a and b)
S
—I
—H
—OCH2CH3


W221 (a and b)
S
—I
—H
—OCF3


W222 (a and b)
S
—I
—H
-tert-butyl


W223 (a and b)
S
—I
—H
-iso-propyl


W224 (a and b)
O
—H
—Cl
—H


W225 (a and b)
O
—H
—Br
—H


W226 (a and b)
O
—H
—F
—H


W227 (a and b)
O
—H
—CH3
—H


W228 (a and b)
O
—H
—CF3
—H


W229 (a and b)
O
—H
—OCH3
—H


W230 (a and b)
O
—H
—OCH2CH3
—H


W231 (a and b)
O
—H
—OCF3
—H


W232 (a and b)
O
—H
-tert-butyl
—H


W233 (a and b)
O
—H
-iso-propyl
—H


W234 (a and b)
O
—H
—CH3
—CH3


W235 (a and b)
O
—H
—H
—H


W236 (a and b)
O
—H
—H
—Cl


W237 (a and b)
O
—H
—H
—Br


W238 (a and b)
O
—H
—H
—F


W239 (a and b)
O
—H
—H
—CH3


W240 (a and b)
O
—H
—H
—CF3


W241 (a and b)
O
—H
—H
—OCH3


W242 (a and b)
O
—H
—H
—OCH2CH3


W243 (a and b)
O
—H
—H
—OCF3


W244 (a and b)
O
—H
—H
-tert-butyl


W245 (a and b)
O
—H
—H
-iso-propyl


W246 (a and b)
O
—Cl
—Cl
—H


W247 (a and b)
O
—Cl
—Br
—H


W248 (a and b)
O
—Cl
—F
—H


W249 (a and b)
O
—Cl
—CH3
—H


W250 (a and b)
O
—Cl
—CF3
—H


W251 (a and b)
O
—Cl
—OCH3
—H


W252 (a and b)
O
—Cl
—OCH2CH3
—H


W253 (a and b)
O
—Cl
—OCF3
—H


W254 (a and b)
O
—Cl
-tert-butyl
—H


W255 (a and b)
O
—Cl
-iso-propyl
—H


W256 (a and b)
O
—Cl
—CH3
—CH3


W257 (a and b)
O
—Cl
—H
—H


W258 (a and b)
O
—Cl
—H
—CH3


W259 (a and b)
O
—Cl
—H
—Cl


W260 (a and b)
O
—Cl
—H
—Br


W261 (a and b)
O
—Cl
—H
—F


W262 (a and b)
O
—Cl
—H
—CF3


W263 (a and b)
O
—Cl
—H
—OCH3


W264 (a and b)
O
—Cl
—H
—OCH2CH3


W265 (a and b)
O
—Cl
—H
—OCF3


W266 (a and b)
O
—Cl
—H
-tert-butyl


W267 (a and b)
O
—Cl
—H
-iso-propyl


W268 (a and b)
O
—Cl
—H
—OCF3


W269 (a and b)
O
—Cl
—H
-tert-butyl


W270 (a and b)
O
—Cl
—H
-iso-propyl


W271 (a and b)
O
—CH3
—Cl
—H


W272 (a and b)
O
—CH3
—Br
—H


W273 (a and b)
O
—CH3
—F
—H


W274 (a and b)
O
—CH3
—CH3
—H


W275 (a and b)
O
—CH3
—CF3
—H


W276 (a and b)
O
—CH3
—OCH3
—H


W277 (a and b)
O
—CH3
—OCH2CH3
—H


W278 (a and b)
O
—CH3
—OCF3
—H


W279 (a and b)
O
—CH3
-tert-butyl
—H


W280 (a and b)
O
—CH3
-iso-propyl
—H


W281 (a and b)
O
—CH3
—CH3
—CH3


W282 (a and b)
O
—CH3
—H
—H


W283 (a and b)
O
—CH3
—H
—Cl


W284 (a and b)
O
—CH3
—H
—Br


W285 (a and b)
O
—CH3
—H
—F


W286 (a and b)
O
—CH3
—H
—CH3


W287 (a and b)
O
—CH3
—H
—CF3


W288 (a and b)
O
—CH3
—H
—OCH3


W289 (a and b)
O
—CH3
—H
—OCH2CH3


W290 (a and b)
O
—CH3
—H
—OCF3


W291 (a and b)
O
—CH3
—H
-tert-butyl


W292 (a and b)
O
—CH3
—H
-iso-propyl


W293 (a and b)
O
—CF3
—Cl
—H


W294 (a and b)
O
—CF3
—Br
—H


W295 (a and b)
O
—CF3
—F
—H


W296 (a and b)
O
—CF3
—CH3
—H


W297 (a and b)
O
—CF3
—CF3
—H


W298 (a and b)
O
—CF3
—OCH3
—H


W299 (a and b)
O
—CF3
—OCH2CH3
—H


W300 (a and b)
O
—CF3
—OCF3
—H


W301 (a and b)
O
—CF3
-tert-butyl
—H


W302 (a and b)
O
—CF3
-iso-propyl
—H


W303 (a and b)
O
—CF3
—CH3
—CH3


W304 (a and b)
O
—CF3
—H
—H


W305 (a and b)
O
—CF3
—H
—Cl


W306 (a and b)
O
—CF3
—H
—Br


W307 (a and b)
O
—CF3
—H
—F


W308 (a and b)
O
—CF3
—H
—CH3


W309 (a and b)
O
—CF3
—H
—CF3


W310 (a and b)
O
—CF3
—H
—OCH3


W311 (a and b)
O
—CF3
—H
—OCH2CH3


W312 (a and b)
O
—CF3
—H
—OCF3


W313 (a and b)
O
—CF3
—H
-tert-butyl


W314 (a and b)
O
—CF3
—H
-iso-propyl


W315 (a and b)
O
—CHF2
—Cl
—H


W316 (a and b)
O
—CHF2
—Br
—H


W317 (a and b)
O
—CHF2
—F
—H


W318 (a and b)
O
—CHF2
—CH3
—H


W319 (a and b)
O
—CHF2
—CF3
—H


W320 (a and b)
O
—CHF2
—OCH3
—H


W321 (a and b)
O
—CHF2
—OCH2CH3
—H


W322 (a and b)
O
—CHF2
—OCF3
—H


W323 (a and b)
O
—CHF2
-tert-butyl
—H


W324 (a and b)
O
—CHF2
-iso-propyl
—H


W325 (a and b)
O
—CHF2
—CH3
—CH3


W326 (a and b)
O
—CHF2
—H
—H


W327 (a and b)
O
—CHF2
—H
—Cl


W328 (a and b)
O
—CHF2
—H
—Br


W329 (a and b)
O
—CHF2
—H
—F


W330 (a and b)
O
—CHF2
—H
—CH3


W331 (a and b)
O
—CHF2
—H
—CF3


W332 (a and b)
O
—CHF2
—H
—OCH3


W333 (a and b)
O
—CHF2
—H
—OCH2CH3


W334 (a and b)
O
—CHF2
—H
—OCF3


W335 (a and b)
O
—CHF2
—H
-tert-butyl


W336 (a and b)
O
—CHF2
—H
-iso-propyl


W337 (a and b)
O
—OH
—Cl
—H


W338 (a and b)
O
—OH
—Br
—H


W339 (a and b)
O
—OH
—F
—H


W340 (a and b)
O
—OH
—CH3
—H


W341 (a and b)
O
—OH
—CF3
—H


W342 (a and b)
O
—OH
—OCH3
—H


W343 (a and b)
O
—OH
—OCH2CH3
—H


W344 (a and b)
O
—OH
—OCF3
—H


W345 (a and b)
O
—OH
-tert-butyl
—H


W346 (a and b)
O
—OH
-iso-propyl
—H


W347 (a and b)
O
—OH
—CH3
—CH3


W348 (a and b)
O
—OH
—H
—H


W349 (a and b)
O
—OH
—H
—Cl


W350 (a and b)
O
—OH
—H
—Br


W351 (a and b)
O
—OH
—H
—F


W352 (a and b)
O
—OH
—H
—CH3


W353 (a and b)
O
—OH
—H
—CF3


W354 (a and b)
O
—OH
—H
—OCH3


W355 (a and b)
O
—OH
—H
—OCH2CH3


W356 (a and b)
O
—OH
—H
—OCF3


W357 (a and b)
O
—OH
—H
-tert-butyl


W358 (a and b)
O
—OH
—H
-iso-propyl


W359 (a and b)
O
—NO2
—Cl
—H


W360 (a and b)
O
—NO2
—Br
—H


W361 (a and b)
O
—NO2
—F
—H


W362 (a and b)
O
—NO2
—CH3
—H


W363 (a and b)
O
—NO2
—CF3
—H


W364 (a and b)
O
—NO2
—OCH3
—H


W365 (a and b)
O
—NO2
—OCH2CH3
—H


W366 (a and b)
O
—NO2
—OCF3
—H


W367 (a and b)
O
—NO2
-tert-butyl
—H


W368 (a and b)
O
—NO2
-iso-propyl
—H


W369 (a and b)
O
—NO2
—CH3
—CH3


W370 (a and b)
O
—NO2
—H
—H


W371 (a and b)
O
—NO2
—H
—Cl


W372 (a and b)
O
—NO2
—H
—Br


W373 (a and b)
O
—NO2
—H
—F


W374 (a and b)
O
—NO2
—H
—CH3


W375 (a and b)
O
—NO2
—H
—CF3


W376 (a and b)
O
—NO2
—H
—OCH3


W377 (a and b)
O
—NO2
—H
—OCH2CH3


W378 (a and b)
O
—NO2
—H
—OCF3


W379 (a and b)
O
—NO2
—H
-tert-butyl


W380 (a and b)
O
—NO2
—H
-iso-propyl


W381 (a and b)
O
—CN
—Br
—H


W382 (a and b)
O
—CN
—Cl
—H


W383 (a and b)
O
—CN
—F
—H


W384 (a and b)
O
—CN
—CH3
—H


W385 (a and b)
O
—CN
—CF3
—H


W386 (a and b)
O
—CN
—OCH3
—H


W387 (a and b)
O
—CN
—OCH2CH3
—H


W388 (a and b)
O
—CN
—OCF3
—H


W389 (a and b)
O
—CN
-tert-butyl
—H


W390 (a and b)
O
—CN
-iso-propyl
—H


W391 (a and b)
O
—CN
—CH3
—CH3


W392 (a and b)
O
—CN
—H
—H


W393 (a and b)
O
—CN
—H
—Cl


W394 (a and b)
O
—CN
—H
—Br


W395 (a and b)
O
—CN
—H
—F


W396 (a and b)
O
—CN
—H
—CH3


W397 (a and b)
O
—CN
—H
—CF3


W398 (a and b)
O
—CN
—H
—OCH3


W399 (a and b)
O
—CN
—H
—OCH2CH3


W400 (a and b)
O
—CN
—H
—OCF3


W401 (a and b)
O
—CN
—H
-tert-butyl


W402 (a and b)
O
—CN
—H
-iso-propyl


W403 (a and b)
O
—Br
—Br
—H


W404 (a and b)
O
—Br
—Cl
—H


W405 (a and b)
O
—Br
—F
—H


W406 (a and b)
O
—Br
—CH3
—H


W407 (a and b)
O
—Br
—CF3
—H


W408 (a and b)
O
—Br
—OCH3
—H


W409 (a and b)
O
—Br
—OCH2CH3
—H


W410 (a and b)
O
—Br
—OCF3
—H


W411 (a and b)
O
—Br
-tert-butyl
—H


W412 (a and b)
O
—Br
-iso-propyl
—H


W413 (a and b)
O
—Br
—CH3
—CH3


W414 (a and b)
O
—Br
—H
—H


W415 (a and b)
O
—Br
—H
—Cl


W416 (a and b)
O
—Br
—H
—Br


W417 (a and b)
O
—Br
—H
—F


W418 (a and b)
O
—Br
—H
—CH3


W419 (a and b)
O
—Br
—H
—CF3


W420 (a and b)
O
—Br
—H
—OCH3


W421 (a and b)
O
—Br
—H
—OCH2CH3


W422 (a and b)
O
—Br
—H
—OCF3


W423 (a and b)
O
—Br
—H
-tert-butyl


W424 (a and b)
O
—Br
—H
-iso-propyl


W425 (a and b)
O
—I
—Cl
—H


W426 (a and b)
O
—I
—Br
—H


W427 (a and b)
O
—I
—F
—H


W428 (a and b)
O
—I
—CH3
—H


W429 (a and b)
O
—I
—CF3
—H


W430 (a and b)
O
—I
—OCH3
—H


W431 (a and b)
O
—I
—OCH2CH3
—H


W432 (a and b)
O
—I
—OCF3
—H


W433 (a and b)
O
—I
-tert-butyl
—H


W434 (a and b)
O
—I
-iso-propyl
—H


W435 (a and b)
O
—I
—CH3
—CH3


W436 (a and b)
O
—I
—H
—H


W437 (a and b)
O
—I
—H
—Cl


W438 (a and b)
O
—I
—H
—Br


W439 (a and b)
O
—I
—H
—F


W440 (a and b)
O
—I
—H
—CH3


W441 (a and b)
O
—I
—H
—CF3


W442 (a and b)
O
—I
—H
—OCH3


W443 (a and b)
O
—I
—H
—OCH2CH3


W444 (a and b)
O
—I
—H
—OCF3


W445 (a and b)
O
—I
—H
-tert-butyl


W446 (a and b)
O
—I
—H
-iso-propyl


W447 (a and b)
NH
—H
—Cl
—H


W448 (a and b)
NH
—H
—Br
—H


W449 (a and b)
NH
—H
—F
—H


W450 (a and lo)
NH
—H
—CH3
—H


W451 (a and b)
NH
—H
—CF3
—H


W452 (a and b)
NH
—H
—OCH3
—H


W453 (a and b)
NH
—H
—OCH2CH3
—H


W454 (a and b)
NH
—H
—OCF3
—H


W455 (a and b)
NH
—H
-tert-butyl
—H


W456 (a and b)
NH
—H
-iso-propyl
—H


W457 (a and b)
NH
—H
—CH3
—CH3


W458 (a and b)
NH
—H
—H
—H


W459 (a and b)
NH
—H
—H
—Cl


W460 (a and b)
NH
—H
—H
—Br


W461 (a and b)
NH
—H
—H
—F


W462 (a and b)
NH
—H
—H
—CH3


W463 (a and b)
NH
—H
—H
—CF3


W464 (a and b)
NH
—H
—H
—OCH3


W465 (a and b)
NH
—H
—H
—OCH2CH3


W466 (a and b)
NH
—H
—H
—OCF3


W467 (a and b)
NH
—H
—H
-tert-butyl


W468 (a and b)
NH
—H
—H
-iso-propyl


W469 (a and b)
NH
—Cl
—Cl
—H


W470 (a and b)
NH
—Cl
—Br
—H


W471 (a and b)
NH
—Cl
—F
—H


W472 (a and b)
NH
—Cl
—CH3
—H


W473 (a and b)
NH
—Cl
—CF3
—H


W474 (a and b)
NH
—Cl
—OCH3
—H


W475 (a and b)
NH
—Cl
—OCH2CH3
—H


W476 (a and b)
NH
—Cl
—OCF3
—H


W477 (a and b)
NH
—Cl
-tert-butyl
—H


W478 (a and b)
NH
—Cl
-iso-propyl
—H


W479 (a and b)
NH
—Cl
—CH3
—CH3


W480 (a and b)
NH
—Cl
—H
—H


W481 (and b)
NH
—Cl
—H
—CH3


W482 (a and b)
NH
—Cl
—H
—Cl


W483 (a and b)
NH
—Cl
—H
—Br


W484 (a and b)
NH
—Cl
—H
—F


W485 (a and b)
NH
—Cl
—H
—CF3


W486 (a and b)
NH
—Cl
—H
—OCH3


W487 (a and b)
NH
—Cl
—H
—OCH2CH3


W488 (a and b)
NH
—Cl
—H
—OCF3


W489 (a and b)
NH
—Cl
—H
-tert-butyl


W490 (a and b)
NH
—Cl
—H
-iso-propyl


W491 (a and b)
NH
—Cl
—H
—OCF3


W492 (a and b)
NH
—Cl
—H
-tert-butyl


W493 (a and b)
NH
—Cl
—H
-iso-propyl


W494 (a and b)
NH
—CH3
—Cl
—H


W495 (a and b)
NH
—CH3
—Br
—H


W496 (a and b)
NH
—CH3
—F
—H


W497 (a and b)
NH
—CH3
—CH3
—H


W498 (a and b)
NH
—CH3
—CF3
—H


W499 (a and b)
NH
—CH3
—OCH3
—H


W500 (a and b)
NH
—CH3
—OCH2CH3
—H


W501 (a and b)
NH
—CH3
—OCF3
—H


W502 (a and b)
NH
—CH3
-tert-butyl
—H


W503 (a and b)
NH
—CH3
-iso-propyl
—H


W504 (a and b)
NH
—CH3
—CH3
—CH3


W505 (a and b)
NH
—CH3
—H
—H


W506 (a and b)
NH
—CH3
—H
—Cl


W507 (a and b)
NH
—CH3
—H
—Br


W508 (a and b)
NH
—CH3
—H
—F


W509 (a and b)
NH
—CH3
—H
—CH3


W510 (a and b)
NH
—CH3
—H
—CF3


W511 (a and b)
NH
—CH3
—H
—OCH3


W512 (a and b)
NH
—CH3
—H
—OCH2CH3


W513 (a and b)
NH
—CH3
—H
—OCF3


W514 (a and b)
NH
—CH3
—H
-tert-butyl


W515 (a and b)
NH
—CH3
—H
-iso-propyl


W516 (a and b)
NH
—CF3
—Cl
—H


W517 (a and b)
NH
—CF3
—Br
—H


W518 (a and b)
NH
—CF3
—F
—H


W519 (a and b)
NH
—CF3
—CH3
—H


W520 (a and b)
NH
—CF3
—CF3
—H


W521 (a and b)
NH
—CF3
—OCH3
—H


W522 (a and b)
NH
—CF3
—OCH2CH3
—H


W523 (a and b)
NH
—CF3
—OCF3
—H


W524 (a and b)
NH
—CF3
-tert-butyl
—H


W525 (a and b)
NH
—CF3
-iso-propyl
—H


W526 (a and b)
NH
—CF3
—CH3
—CH3


W527 (a and b)
NH
—CF3
—H
—H


W528 (a and b)
NH
—CF3
—H
—Cl


W529 (a and b)
NH
—CF3
—H
—Br


W530 (a and b)
NH
—CF3
—H
—F


W531 (a and b)
NH
—CF3
—H
—CH3


W532 (a and b)
NH
—CF3
—H
—CF3


W533 (a and b)
NH
—CF3
—H
—OCH3


W534 (a and b)
NH
—CF3
—H
—OCH2CH3


W535 (a and b)
NH
—CF3
—H
—OCF3


W536 (a and b)
NH
—CF3
—H
-tert-butyl


W537 (a and b)
NH
—CF3
—H
-iso-propyl


W538 (a and b)
NH
—CHF2
—Cl
—H


W539 (a and b)
NH
—CHF2
—Br
—H


W540 (a and b)
NH
—CHF2
—F
—H


W541 (a and b)
NH
—CHF2
—CH3
—H


W542 (a and b)
NH
—CHF2
—CF3
—H


W543 (a and b)
NH
—CHF2
—OCH3
—H


W544 (a and b)
NH
—CHF2
—OCH2CH3
—H


W545 (a and b)
NH
—CHF2
—OCF3
—H


W546 (a and b)
NH
—CHF2
-tert-butyl
—H


W547 (a and b)
NH
—CHF2
-iso-propyl
—H


W548 (a and b)
NH
—CHF2
—CH3
—CH3


W549 (a and b)
NH
—CHF2
—H
—H


W550 (a and b)
NH
—CHF2
—H
—Cl


W551 (a and b)
NH
—CHF2
—H
—Br


W552 (a and b)
NH
—CHF2
—H
—F


W553 (a and b)
NH
—CHF2
—H
—CH3


W554 (a and b)
NH
—CHF2
—H
—CF3


W555 (a and b)
NH
—CHF2
—H
—OCH3


W556 (a and b)
NH
—CHF2
—H
—OCH2CH3


W557 (a and b)
NH
—CHF2
—H
—OCF3


W558 (a and b)
NH
—CHF2
—H
-tert-butyl


W559 (a and b)
NH
—CHF2
—H
-iso-propyl


W560 (a and b)
NH
—OH
—Cl
—H


W561 (a and b)
NH
—OH
—Br
—H


W562 (a and b)
NH
—OH
—F
—H


W563 (a and b)
NH
—OH
—CH3
—H


W564 (a and b)
NH
—OH
—CF3
—H


W565 (a and b)
NH
—OH
—OCH3
—H


W566 (a and b)
NH
—OH
—OCH2CH3
—H


W567 (a and b)
NH
—OH
—OCF3
—H


W568 (a and b)
NH
—OH
-tert-butyl
—H


W569 (a and b)
NH
—OH
-iso-propyl
—H


W570 (a and b)
NH
—OH
—CH3
—CH3


W571 (a and b)
NH
—OH
—H
—H


W572 (a and b)
NH
—OH
—H
—Cl


W573 (a and b)
NH
—OH
—H
—Br


W574 (a and b)
NH
—OH
—H
—F


W575 (a and b)
NH
—OH
—H
—CH3


W576 (a and b)
NH
—OH
—H
—CF3


W577 (a and b)
NH
—OH
—H
—OCH3


W578 (a and b)
NH
—OH
—H
—OCH2CH3


W579 (a and b)
NH
—OH
—H
—OCF3


W580 (a and b)
NH
—OH
—H
-tert-butyl


W581 (a and b)
NH
—OH
—H
-iso-propyl


W582 (a and b)
NH
—NO2
—Cl
—H


W583 (a and b)
NH
—NO2
—Br
—H


W584 (a and b)
NH
—NO2
—F
—H


W585 (a and b)
NH
—NO2
—CH3
—H


W586 (a and b)
NH
—NO2
—CF3
—H


W587 (a and b)
NH
—NO2
—OCH3
—H


W588 (a and b)
NH
—NO2
—OCH2CH3
—H


W589 (a and b)
NH
—NO2
—OCF3
—H


W590 (a and b)
NH
—NO2
-tert-butyl
—H


W591 (a and b)
NH
—NO2
-iso-propyl
—H


W592 (a and b)
NH
—NO2
—CH3
—CH3


W593 (a and b)
NH
—NO2
—H
—H


W594 (a and b)
NH
—NO2
—H
—Cl


W595 (a and b)
NH
—NO2
—H
—Br


W596 (a and b)
NH
—NO2
—H
—F


W597 (a and b)
NH
—NO2
—H
—CH3


W598 (a and b)
NH
—NO2
—H
—CF3


W599 (a and b)
NH
—NO2
—H
—OCH3


W600 (a and b)
NH
—NO2
—H
—OCH2CH3


W601 (a and b)
NH
—NO2
—H
—OCF3


W602 (a and b)
NH
—NO2
—H
-tert-butyl


W603 (a and b)
NH
—NO2
—H
-iso-propyl


W604 (a and b)
NH
—CN
—Br
—H


W605 (a and b)
NH
—CN
—Cl
—H


W606 (a and b)
NH
—CN
—F
—H


W607 (a and b)
NH
—CN
—CH3
—H


W608 (a and b)
NH
—CN
—CF3
—H


W609 (a and b)
NH
—CN
—OCH3
—H


W610 (a and b)
NH
—CN
—OCH2CH3
—H


W611 (a and b)
NH
—CN
—OCF3
—H


W612 (a and b)
NH
—CN
-tert-butyl
—H


W613 (a and b)
NH
—CN
-iso-propyl
—H


W614 (a and b)
NH
—CN
—CH3
—CH3


W615 (a and b)
NH
—CN
—H
—H


W616 (a and b)
NH
—CN
—H
—Cl


W617 (a and b)
NH
—CN
—H
—Br


W618 (a and b)
NH
—CN
—H
—F


W619 (a and b)
NH
—CN
—H
—CH3


W620 (a and b)
NH
—CN
—H
—CF3


W621 (a and b)
NH
—CN
—H
—OCH3


W622 (a and b)
NH
—CN
—H
—OCH2CH3


W623 (a and b)
NH
—CN
—H
—OCF3


W624 (a and b)
NH
—CN
—H
-tert-butyl


W625 (a and b)
NH
—CN
—H
-iso-propyl


W626 (a and b)
NH
—Br
—Br
—H


W627 (a and b)
NH
—Br
—Cl
—H


W628 (a and b)
NH
—Br
—F
—H


W629 (a and b)
NH
—Br
—CH3
—H


W630 (a and b)
NH
—Br
—CF3
—H


W631 (a and b)
NH
—Br
—OCH3
—H


W632 (a and b)
NH
—Br
—OCH2CH3
—H


W633 (a and b)
NH
—Br
—OCF3
—H


W634 (a and b)
NH
—Br
-tert-butyl
—H


W635 (a and b)
NH
—Br
-iso-propyl
—H


W636 (a and b)
NH
—Br
—CH3
—CH3


W637 (a and b)
NH
—Br
—H
—H


W638 (a and b)
NH
—Br
—H
—Cl


W639 (a and b)
NH
—Br
—H
—Br


W640 (a and b)
NH
—Br
—H
—F


W641 (a and b)
NH
—Br
—H
—CH3


W642 (a and b)
NH
—Br
—H
—CF3


W643 (a and b)
NH
—Br
—H
—OCH3


W644 (a and b)
NH
—Br
—H
—OCH2CH3


W645 (a and b)
NH
—Br
—H
—OCF3


W646 (a and b)
NH
—Br
—H
-tert-butyl


W647 (a and b)
NH
—Br
—H
-iso-propyl


W648 (a and b)
NH
—I
—Cl
—H


W649 (a and b)
NH
—I
—Br
—H


W650 (a and b)
NH
—I
—F
—H


W651 (a and b)
NH
—I
—CH3
—H


W652 (a and b)
NH
—I
—CF3
—H


W653 (a and b)
NH
—I
—OCH3
—H


W654 (a and b)
NH
—I
—OCH2CH3
—H


W655 (a and b)
NH
—I
—OCF3
—H


W656 (a and b)
NH
—I
-tert-butyl
—H


W657 (a and b)
NH
—I
-iso-propyl
—H


W658 (a and b)
NH
—I
—CH3
—CH3


W659 (a and b)
NH
—H
—H



W660 (a and b)
NH
—I
—H
—Cl


W661 (a and b)
NH
—I
—H
—Br


W662 (a and b)
NH
—I
—H
—F


W663 (a and b)
NH
—I
—H
—CH3


W664 (a and b)
NH
—I
—H
—CF3


W665 (a and b)
NH
—I
—H
—OCH3


W666 (a and b)
NH
—I
—H
—OCH2CH3


W667 (a and b)
NH
—I
—H
—OCF3


W668 (a and b)
NH
—I
—H
-tert-butyl


W669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 24








(Ix)




embedded image













and pharmaceutically acceptable salts thereof, wherein:









Compound
R1
R8a





X1 (a and b)
—H
—H


X2 (a and b)
—H
-tert-butyl


X3 (a and b)
—H
-iso-butyl


X4 (a and b)
—H
-sec-butyl


X5 (a and b)
—H
-iso-propyl


X6 (a and b)
—H
-n-propyl


X7 (a and b)
—H
-cyclohexyl


X8 (a and b)
—H
-tert-butoxy


X9 (a and b)
—H
-isopropoxy


X10 (a and b)
—H
—CF3


X11 (a and b)
—H
—CH2CF3


X12 (a and b)
—H
—OCF3


X13 (a and b)
—H
—Cl


X14 (a and b)
—H
—Br


X15 (a and b)
—H
—I


X16 (a and b)
—H
-n-butyl


X17 (a and b)
—H
—CH3


X18 (a and b)
—H
—SCF3


X19 (a and b)
—H
—N(CH2CH3)2


X20 (a and b)
—H
—OCF2CHF2


X21 (a and b)
—H
—C(OH)(CF3)2


X22 (a and b)
—H
-(1,1-dimethyl-pentyl)


X23 (a and b)
—H
-(1,1-dimethyl-acetic acid) ethyl ester


X24 (a and b)
—H
—N-piperidinyl


X25 (a and b)
—Cl
—H


X26 (a and b)
—Cl
-tert-butyl


X27 (a and b)
—Cl
-iso-butyl


X28 (a and b)
—Cl
-sec-butyl


X29 (a and b)
—Cl
-iso-propyl


X30 (a and b)
—Cl
-n-propyl


X31 (a and b)
—Cl
-cyclohexyl


X32 (a and b)
—Cl
-tert-butoxy


X33 (a and b)
—Cl
-isopropoxy


X34 (a and b)
—Cl
—CF3


X35 (a and b)
—Cl
—CH2CF3


X36 (a and b)
—Cl
—OCF3


X37 (a and b)
—Cl
—Cl


X38 (a and b)
—Cl
—Br


X39 (a and b)
—Cl
—I


X40 (a and b)
—Cl
-n-butyl


X41 (a and b)
—Cl
—CH3


X42 (a and b)
—Cl
—SCF3


X43 (a and b)
—Cl
—N(CH2CH3)2


X44 (a and b)
—Cl
—OCF2CHF2


X45 (a and b)
—Cl
—C(OH)(CF3)2


X46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)


X47 (a and b)
—Cl
-(1,1-dimcthyl-acetic acid) ethyl ester


X48 (a and b)
—Cl
—N-piperidinyl


X49 (a and b)
—F
—H


X50 (a and b)
—F
-tert-butyl


X51 (a and b)
—F
-iso-butyl


X52 (a and b)
—F
-sec-butyl


X53 (a and b)
—F
-iso-propyl


X54 (a and b)
—F
-n-propyl


X55 (a and b)
—F
-cyclohexyl


X56 (a and b)
—F
-tert-butoxy


X57 (a and b)
—F
-isopropoxy


X58 (a and b)
—F
—CF3


X59 (a and b)
—F
—CH2CF3


X60 (a and b)
—F
—OCF3


X61 (a and b)
—F
—Cl


X62 (a and b)
—F
—Br


X63 (a and b)
—F
—I


X64 (a and b)
—F
-n-butyl


X65 (a and b)
—F
—CH3


X66 (a and b)
—F
—SCF3


X67 (a and b)
—F
—N(CH2CH3)2


X68 (a and b)
—F
—OCF2CHF2


X69 (a and b)
—F
—C(OH)(CF3)2


X70 (a and b)
—F
-(1,1-dimethyl-pentyl)


X71 (a and b)
—F
-(1,1-dimethyl-acetic acid) ethyl ester


X72 (a and b)
—F
—N-piperidinyl


X73 (a and b)
—CH3
—H


X74 (a and b)
—CH3
-iso-butyl


X75 (a and b)
—CH3
-tert-butyl


X76 (a and b)
—CH3
-sec-butyl


X77 (a and b)
—CH3
-iso-propyl


X78 (a and b)
—CH3
-n-propyl


X79 (a and b)
—CH3
-cyclohexyl


X80 (a and b)
—CH3
-tert-butoxy


X81 (a and b)
—CH3
-isopropoxy


X82 (a and b)
—CH3
—CF3


X83 (a and b)
—CH3
—CH2CF3


X84 (a and b)
—CH3
—OCF3


X85 (a and b)
—CH3
—Cl


X86 (a and b)
—CH3
—Br


X87 (a and b)
—CH3
—I


X88 (a and b)
—CH3
-n-butyl


X89 (a and b)
—CH3
—CH3


X90 (a and b)
—CH3
—SCF3


X91 (a and b)
—CH3
—N(CH2CH3)2


X92 (a and b)
—CH3
—OCF2CHF2


X93 (a and b)
—CH3
—C(OH)(CF3)2


X94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)


X95 (a and b)
—CH3
-(1,1-dimethyl-acetic acid) ethyl ester


X96 (a and b)
—CH3
—N-piperidinyl


X97 (a and b)
—CF3
—H


X98 (a and b)
—CF3
-tert-butyl


X99 (a and b)
—CF3
-iso-butyl


X100 (a and b)
—CF3
-sec-butyl


X101 (a and b)
—CF3
-iso-propyl


X102 (a and b)
—CF3
-n-propyl


X103 (a and b)
—CF3
-cyclohexyl


X104 (a and b)
—CF3
-tert-butoxy


X105 (a and b)
—CF3
-isopropoxy


X106 (a and b)
—CF3
—CF3


X107 (a and b)
—CF3
—CH2CF3


X108 (a and b)
—CF3
—OCF3


X109 (a and b)
—CF3
—Cl


X110 (a and b)
—CF3
—Br


X111 (a and b)
—CF3
—I


X112 (a and b)
—CF3
-n-butyl


X113 (a and b)
—CF3
—CH3


X114 (a and b)
—CF3
—SCF3


X115 (a and b)
—CF3
—N(CH2CH3)2


X116 (a and b)
—CF3
—OCF2CHF2


X117 (a and b)
—CF3
—C(OH)(CF3)2


X118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)


X119 (a and b)
—CF3
-(1,1-dimethyl-acetic acid) ethyl ester


X120 (a and b)
—CF3
—N-piperidinyl


X121 (a and b)
—CHF2
-tert-butyl


X122 (a and b)
—CHF2
—H


X123 (a and b)
—CHF2
-iso-butyl


X124 (a and b)
—CHF2
-sec-butyl


X125 (a and b)
—CHF2
-iso-propyl


X126 (a and b)
—CHF2
-n-propyl


X127 (a and b)
—CHF2
-cyclohexyl


X128 (a and b)
—CHF2
-tert-butoxy


X129 (a and b)
—CHF2
-isopropoxy


X130 (a and b)
—CHF2
—CF3


X131 (a and b)
—CHF2
—CH2CF3


X132 (a and b)
—CHF2
—OCF3


X133 (a and b)
—CHF2
—Cl


X134 (a and b)
—CHF2
—Br


X135 (a and b)
—CHF2
—I


X136 (a and b)
—CHF2
-n-butyl


X137 (a and b)
—CHF2
—CH3


X138 (a and b)
—CHF2
—SCF3


X139 (a and b)
—CHF2
—N(CH2CH3)2


X140 (a and b)
—CHF2
—OCF2CHF2


X141 (a and b)
—CHF2
—C(OH)(CF3)2


X142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)


X143 (a and b)
—CHF2
-(1,1-dimethyl-acetic acid) ethyl ester


X144 (a and b)
—CHF2
—N-piperidinyl


X145 (a and b)
—OH
—H


X146 (a and b)
—OH
-tert-butyl


X147 (a and b)
—OH
-iso-butyl


X148 (a and b)
—OH
-sec-butyl


X149 (a and b)
—OH
-iso-propyl


X150 (a and b)
—OH
-n-propyl


X151 (a and b)
—OH
-cyclohexyl


X152 (a and b)
—OH
-tert-butoxy


X153 (a and b)
—OH
-isopropoxy


X154 (a and b)
—OH
—CF3


X155 (a and b)
—OH
—CH2CF3


X156 (a and b)
—OH
—OCF3


X157 (a and b)
—OH
—Cl


X158 (a and b)
—OH
—Br


X159 (a and b)
—OH
—I


X160 (a and b)
—OH
-n-butyl


X161 (a and b)
—OH
—CH3


X162 (a and b)
—OH
—SCF3


X163 (a and b)
—OH
—N(CH2CH3)2


X164 (a and b)
—OH
—OCF2CHF2


X165 (a and b)
—OH
—C(OH)(CF3)2


X166 (a and b)
—OH
-(1,1-dimethyl-pentyl)


X167 (a and b)
—OH
-(1,1-dimethyl-acetic acid) ethyl ester


X168 (a and b)
—OH
—N-piperidinyl


X169 (a and b)
—NO2
—H


X170 (a and b)
—NO2
-tert-butyl


X171 (a and b)
—NO2
-iso-butyl


X172 (a and b)
—NO2
-sec-butyl


X173 (a and b)
—NO2
-iso-propyl


X174 (a and b)
—NO2
-n-propyl


X175 (a and b)
—NO2
-cyclohexyl


X176 (a and b)
—NO2
-tert-butoxy


X177 (a and b)
—NO2
-isopropoxy


X178 (a and b)
—NO2
—CF3


X179 (a and b)
—NO2
—CH2CF3


X180 (a and b)
—NO2
—OCF3


X181 (a and b)
—NO2
—Cl


X182 (a and b)
—NO2
—Br


X183 (a and b)
—NO2
—I


X184 (a and b)
—NO2
-n-butyl


X185 (a and b)
—NO2
—CH3


X186 (a and b)
—NO2
—SCF3


X187 (a and b)
—NO2
—N(CH2CH3)2


X188 (a and b)
—NO2
—OCF2CHF2


X189 (a and b)
—NO2
—C(OH)(CF3)2


X190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)


X191 (a and b)
—NO2
-(1,1-dimethyl-acetic acid) ethyl ester


X192 (a and b)
—NO2
—N-piperidinyl


X193 (a and b)
—CN
—H


X194 (a and b)
—CN
-tert-butyl


X195 (a and b)
—CN
-iso-butyl


X196 (a and b)
—CN
-sec-butyl


X197 (a and b)
—CN
-iso-propyl


X198 (a and b)
—CN
-n-propyl


X199 (a and b)
—CN
-cyclohexyl


X200 (a and b)
—CN
-tert-butoxy


X201 (a and b)
—CN
-isopropoxy


X202 (a and b)
—CN
—CF3


X203 (a and b)
—CN
—CH2CF3


X204 (a and b)
—CN
—OCF3


X205 (a and b)
—CN
—Cl


X206 (a and b)
—CN
—Br


X207 (a and b)
—CN
—I


X208 (a and b)
—CN
-n-butyl


X209 (a and b)
—CN
—CH3


X210 (a and b)
—CN
—SCF3


X211 (a and b)
—CN
—N(CH2CH3)2


X212 (a and b)
—CN
—OCF2CHF2


X213 (a and b)
—CN
—C(OH)(CF3)2


X214 (a and b)
—CN
-(1,1-dimethyl-pentyl)


X215 (a and b)
—CN
-(1,1-dimethyl-acetic acid) ethyl ester


X216 (a and b)
—CN
—N-piperidinyl


X217 (a and b)
—Br
—H


X218 (a and b)
—Br
-tert-butyl


X219 (a and b)
—Br
-iso-butyl


X220 (a and b)
—Br
-sec-butyl


X221 (a and b)
—Br
-iso-propyl


X222 (a and b)
—Br
-n-propyl


X223 (a and b)
—Br
-cyclohexyl


X224 (a and b)
—Br
-tert-butoxy


X225 (a and b)
—Br
-isopropoxy


X226 (a and b)
—Br
—CF3


X227 (a and b)
—Br
—CH2CF3


X228 (a and b)
—Br
—OCF3


X229 (a and b)
—Br
—Cl


X230 (a and b)
—Br
—Br


X231 (a and b)
—Br
—I


X232 (a and b)
—Br
-n-butyl


X233 (a and b)
—Br
—CH3


X234 (a and b)
—Br
—SCF3


X235 (a and b)
—Br
—N(CH2CH3)2


X236 (a and b)
—Br
—OCF2CHF2


X237 (a and b)
—Br
—C(OH)(CF3)2


X238 (a and b)
—Br
-(1,1-dimethyl-pentyl)


X239 (a and b)
—Br
-(1,1-dimethyl-acetic acid) ethyl ester


X240 (a and b)
—Br
—N-piperidinyl


X241 (a and b)
—I
-tert-butyl


X242 (a and b)
—I
—H


X243 (a and b)
—I
-iso-butyl


X244 (a and b)
—I
-sec-butyl


X245 (a and b)
—I
-iso-propyl


X246 (a and b)
—I
-n-propyl


X247 (a and b)
—I
-cyclohexyl


X248 (a and b)
—I
-tert-butoxy


X249 (a and b)
—I
-isopropoxy


X250 (a and b)
—I
—CF3


X251 (a and b)
—I
—CH2CF3


X252 (a and b)
—I
—OCF3


X253 (a and b)
—I
—Cl


X254 (a and b)
—I
—Br


X255 (a and b)
—I
—I


X256 (a and b)
—I
-n-butyl


X257 (a and b)
—I
—CH3


X258 (a and b)
—I
—SCF3


X259 (a and b)
—I
—N(CH2CH3)2


X260 (a and b)
—I
—OCF2CHF2


X261 (a and b)
—I
—C(OH)(CF3)2


X262 (a and b)
—I
-(1,1-dimethyl-pentyl)


X263 (a and b)
—I
-(1,1-dimethyl-acetic acid) ethyl ester


X264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 25








(Iy)




embedded image













and pharmaceutically acceptable salts thereof, wherein:









Compound
R1
R8a





Y1 (a and b)
—H
—H


Y2 (a and b)
—H
-tert-butyl


Y3 (a and b)
—H
-iso-butyl


Y4 (a and b)
—H
-sec-butyl


Y5 (a and b)
—H
-iso-propyl


Y6 (a and b)
—H
-n-propyl


Y7 (a and b)
—H
-cyclohexyl


Y8 (a and b)
—H
-tert-butoxy


Y9 (a and b)
—H
-isopropoxy


Y10 (a and b)
—H
—CF3


Y11 (a and b)
—H
—CH2CF3


Y12 (a and b)
—H
—OCF3


Y13 (a and b)
—H
—Cl


Y14 (a and b)
—H
—Br


Y15 (a and b)
—H
—I


Y16 (a and b)
—H
-n-butyl


Y17 (a and b)
—H
—CH3


Y18 (a and b)
—H
—SCF3


Y19 (a and b)
—H
—N(CH2CH3)2


Y20 (a and b)
—H
—OCF2CHF2


Y21 (a and b)
—H
—C(OH)(CF3)2


Y22 (a and b)
—H
-(1,1-dimethyl-pentyl)


Y23 (a and b)
—H
-(1,1-dimethyl-acetic acid) ethyl ester


Y24 (a and b)
—H
—N-piperidinyl


Y25 (a and b)
—Cl
—H


Y26 (a and b)
—Cl
-tert-butyl


Y27 (a and b)
—Cl
-iso-butyl


Y28 (a and b)
—Cl
-sec-butyl


Y29 (a and b)
—Cl
-iso-propyl


Y30 (a and b)
—Cl
-n-propyl


Y31 (a and b)
—Cl
-cyclohexyl


Y32 (a and b)
—Cl
-tert-butoxy


Y33 (a and b)
—Cl
-isopropoxy


Y34 (a and b)
—Cl
—CF3


Y35 (a and b)
—Cl
—CH2CF3


Y36 (a and b)
—Cl
—OCF3


Y37 (a and b)
—Cl
—Cl


Y38 (a and b)
—Cl
—Br


Y39 (a and b)
—Cl
—I


Y40 (a and b)
—Cl
-n-butyl


Y41 (a and b)
—Cl
—CH3


Y42 (a and b)
—Cl
—SCF3


Y43 (a and b)
—Cl
—N(CH2CH3)2


Y44 (a and b)
—Cl
—OCF2CHF2


Y45 (a and b)
—Cl
—C(OH)(CF3)2


Y46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)


Y47 (a and b)
—Cl
-(1,1-dimethyl-acetic acid) ethyl ester


Y48 (a and b)
—Cl
—N-piperidinyl


Y49 (a and b)
—F
—H


Y50 (a and b)
—F
-tert-butyl


Y51 (a and b)
—F
-iso-butyl


Y52 (a and b)
—F
-sec-butyl


Y53 (a and b)
—F
-iso-propyl


Y54 (a and b)
—F
-n-propyl


Y55 (a and b)
—F
-cyclohexyl


Y56 (a and b)
—F
-tert-butoxy


Y57 (a and b)
—F
-isopropoxy


Y58 (a and b)
—F
—CF3


Y59 (a and b)
—F
—CH2CF3


Y60 (a and b)
—F
—OCF3


Y61 (a and b)
—F
—Cl


Y62 (a and b)
—F
—Br


Y63 (a and b)
—F
—I


Y64 (a and b)
—F
-n-butyl


Y65 (a and b)
—F
—CH3


Y66 (a and b)
—F
—SCF3


Y67 (a and b)
—F
—N(CH2CH3)2


Y68 (a and b)
—F
—OCF2CHF2


Y69 (a and b)
—F
—C(OH)(CF3)2


Y70 (a and b)
—F
-(1,1-dimethyl-pentyl)


Y71 (a and b)
—F
-(1,1-dimethyl-acetic acid) ethyl ester


Y72 (a and b)
—F
—N-piperidinyl


Y73 (a and b)
—CH3
—H


Y74 (a and b)
—CH3
-iso-butyl


Y75 (a and b)
—CH3
-tert-butyl


Y76 (a and b)
—CH3
-sec-butyl


Y77 (a and b)
—CH3
-iso-propyl


Y78 (a and b)
—CH3
-n-propyl


Y79 (a and b)
—CH3
-cyclohexyl


Y80 (a and b)
—CH3
-tert-butoxy


Y81 (a and b)
—CH3
-isopropoxy


Y82 (a and b)
—CH3
—CF3


Y83 (a and b)
—CH3
—CH2CF3


Y84 (a and b)
—CH3
—OCF3


Y85 (a and b)
—CH3
—Cl


Y86 (a and b)
—CH3
—Br


Y87 (a and b)
—CH3
—I


Y88 (a and b)
—CH3
-n-butyl


Y89 (a and b)
—CH3
—CH3


Y90 (a and b)
—CH3
—SCF3


Y91 (a and b)
—CH3
—N(CH2CH3)2


Y92 (a and b)
—CH3
—OCF2CHF2


Y93 (a and b)
—CH3
—C(OH)(CF3)2


Y94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)


Y95 (a and b)
—CH3
-(1,1-dimethyl-acetic acid) ethyl ester


Y96 (a and b)
—CH3
—N-piperidinyl


Y97 (a and b)
—CF3
—H


Y98 (a and b)
—CF3
-tert-butyl


Y99 (a and b)
—CF3
-iso-butyl


Y100 (a and b)
—CF3
-sec-butyl


Y101 (a and b)
—CF3
-iso-propyl


Y102 (a and b)
—CF3
-n-propyl


Y103 (a and b)
—CF3
-cyclohexyl


Y104 (a and b)
—CF3
-tert-butoxy


Y105 (a and b)
—CF3
-isopropoxy


Y106 (a and b)
—CF3
—CF3


Y107 (a and b)
—CF3
—CH2CF3


Y108 (a and b)
—CF3
—OCF3


Y109 (a and b)
—CF3
—Cl


Y110 (a and b)
—CF3
—Br


Y111 (a and b)
—CF3
—I


Y112 (a and b)
—CF3
-n-butyl


Y113 (a and b)
—CF3
—CH3


Y114 (a and b)
—CF3
—SCF3


Y115 (a and b)
—CF3
—N(CH2CH3)2


Y116 (a and b)
—CF3
—OCF2CHF2


Y117 (a and b)
—CF3
—C(OH)(CF3)2


Y118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)


Y119 (a and b)
—CF3
-(1,1-dimethyl-acetic acid) ethyl ester


Y120 (a and b)
—CF3
—N-piperidinyl


Y121 (a and b)
—CHF2
-tert-butyl


Y122 (a and b)
—CHF2
—H


Y123 (a and b)
—CHF2
-iso-butyl


Y124 (a and b)
—CHF2
-sec-butyl


Y125 (a and b)
—CHF2
-iso-propyl


Y126 (a and b)
—CHF2
-n-propyl


Y127 (a and b)
—CHF2
-cyclohexyl


Y128 (a and b)
—CHF2
-tert-butoxy


Y129 (a and b)
—CHF2
-isopropoxy


Y130 (a and b)
—CHF2
—CF3


Y131 (a and b)
—CHF2
—CH2CF3


Y132 (a and b)
—CHF2
—OCF3


Y133 (a and b)
—CHF2
—Cl


Y134 (a and b)
—CHF2
—Br


Y135 (a and b)
—CHF2
—I


Y136 (a and b)
—CHF2
-n-butyl


Y137 (a and b)
—CHF2
—CH3


Y138 (a and b)
—CHF2
—SCF3


Y139 (a and b)
—CHF2
—N(CH2CH3)2


Y140 (a and b)
—CHF2
—OCF2CHF2


Y141 (a and b)
—CHF2
—C(OH)(CF3)2


Y142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)


Y143 (a and b)
—CHF2
-(1,1-dimethyl-acetic acid) ethyl ester


Y144 (a and b)
—CHF2
—N-piperidinyl


Y145 (a and b)
—OH
—H


Y146 (a and b)
—OH
-tert-butyl


Y147 (a and b)
—OH
-iso-butyl


Y148 (a and b)
—OH
-sec-butyl


Y149 (a and b)
—OH
-iso-propyl


Y150 (a and b)
—OH
-n-propyl


Y151 (a and b)
—OH
-cyclohexyl


Y152 (a and b)
—OH
-tert-butoxy


Y153 (a and b)
—OH
-isopropoxy


Y154 (a and b)
—OH
—CF3


Y155 (a and b)
—OH
—CH2CF3


Y156 (a and b)
—OH
—OCF3


Y157 (a and b)
—OH
—Cl


Y158 (a and b)
—OH
—Br


Y159 (a and b)
—OH
—I


Y160 (a and b)
—OH
-n-butyl


Y161 (a and b)
—OH
—CH3


Y162 (a and b)
—OH
—SCF3


Y163 (a and b)
—OH
—N(CH2CH3)2


Y164 (a and b)
—OH
—OCF2CHF2


Y165 (a and b)
—OH
—C(OH)(CF3)2


Y166 (a and b)
—OH
-(1,1-dimethyl-pentyl)


Y167 (a and b)
—OH
-(1,1-dimethyl-acetic acid) ethyl ester


Y168 (a and b)
—OH
—N-piperidinyl


Y169 (a and b)
—NO2
—H


Y170 (a and b)
—NO2
-tert-butyl


Y171 (a and b)
—NO2
-iso-butyl


Y172 (a and b)
—NO2
-sec-butyl


Y173 (a and b)
—NO2
-iso-propyl


Y174 (a and b)
—NO2
-n-propyl


Y175 (a and b)
—NO2
-cyclohexyl


Y176 (a and b)
—NO2
-tert-butoxy


Y177 (a and b)
—NO2
-isopropoxy


Y178 (a and b)
—NO2
—CF3


Y179 (a and b)
—NO2
—CH2CF3


Y180 (a and b)
—NO2
—OCF3


Y181 (a and b)
—NO2
—Cl


Y182 (a and b)
—NO2
—Br


Y183 (a and b)
—NO2
—I


Y184 (a and b)
—NO2
-n-butyl


Y185 (a and b)
—NO2
—CH3


Y186 (a and b)
—NO2
—SCF3


Y187 (a and b)
—NO2
—N(CH2CH3)2


Y188 (a and b)
—NO2
—OCF2CHF2


Y189 (a and b)
—NO2
—C(OH)(CF3)2


Y190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)


Y191 (a and b)
—NO2
-(1,1-dimethyl-acetic acid) ethyl ester


Y192 (a and b)
—NO2
—N-piperidinyl


Y193 (a and b)
—CN
—H


Y194 (a and b)
—CN
-tert-butyl


Y195 (a and b)
—CN
-iso-butyl


Y196 (a and b)
—CN
-sec-butyl


Y197 (a and b)
—CN
-iso-propyl


Y198 (a and b)
—CN
-n-propyl


Y199 (a and b)
—CN
-cyclohexyl


Y200 (a and b)
—CN
-tert-butoxy


Y201 (a and b)
—CN
-isopropoxy


Y202 (a and b)
—CN
—CF3


Y203 (a and b)
—CN
—CH2CF3


Y204 (a and b)
—CN
—OCF3


Y205 (a and b)
—CN
—Cl


Y206 (a and b)
—CN
—Br


Y207 (a and b)
—CN
—I


Y208 (a and b)
—CN
-n-butyl


Y209 (a and b)
—CN
—CH3


Y210 (a and b)
—CN
—SCF3


Y211 (a and b)
—CN
—N(CH2CH3)2


Y212 (a and b)
—CN
—OCF2CHF2


Y213 (a and b)
—CN
—C(OH)(CF3)2


Y214 (a and b)
—CN
-(1,1-dimethyl-pentyl)


Y215 (a and b)
—CN
-(1,1-dimethyl-acetic acid) ethyl ester


Y216 (a and b)
—CN
—N-piperidinyl


Y217 (a and b)
—Br
—H


Y218 (a and b)
—Br
-tert-butyl


Y219 (a and b)
—Br
-iso-butyl


Y220 (a and b)
—Br
-sec-butyl


Y221 (a and b)
—Br
-iso-propyl


Y222 (a and b)
—Br
-n-propyl


Y223 (a and b)
—Br
-cyclohexyl


Y224 (a and b)
—Br
-tert-butoxy


Y225 (a and b)
—Br
-isopropoxy


Y226 (a and b)
—Br
—CF3


Y227 (a and b)
—Br
—CH2CF3


Y228 (a and b)
—Br
—OCF3


Y229 (a and b)
—Br
—Cl


Y230 (a and b)
—Br
—Br


Y231 (a and b)
—Br
—I


Y232 (a and b)
—Br
-n-butyl


Y233 (a and b)
—Br
—CH3


Y234 (a and b)
—Br
—SCF3


Y235 (a and b)
—Br
—N(CH2CH3)2


Y236 (a and b)
—Br
—OCF2CHF2


Y237 (a and b)
—Br
—C(OH)(CF3)2


Y238 (a and b)
—Br
-(1,1-dimethyl-pentyl)


Y239 (a and b)
—Br
-(1,1-dimethyl-acetic acid) ethyl ester


Y240 (a and b)
—Br
—N-piperidinyl


Y241 (a and b)
—I
-tert-butyl


Y242 (a and b)
—I
—H


Y243 (a and b)
—I
-iso-butyl


Y244 (a and b)
—I
-sec-butyl


Y245 (a and b)
—I
-iso-propyl


Y246 (a and b)
—I
-n-propyl


Y247 (a and b)
—I
-cyclohexyl


Y248 (a and b)
—I
-tert-butoxy


Y249 (a and b)
—I
-isopropoxy


Y250 (a and b)
—I
—CF3


Y251 (a and b)
—I
—CH2CF3


Y252 (a and b)
—I
—OCF3


Y253 (a and b)
—I
—Cl


Y254 (a and b)
—I
—Br


Y255 (a and b)
—I
—I


Y256 (a and b)
—I
-n-butyl


Y257 (a and b)
—I
—CH3


Y258 (a and b)
—I
—SCF3


Y259 (a and b)
—I
—N(CH2CH3)2


Y260 (a and b)
—I
—OCF2CHF2


Y261 (a and b)
—I
—C(OH)(CF3)2


Y262 (a and b)
—I
-(1,1-dimethyl-pentyl)


Y263 (a and b)
—I
-(1,1-dimethyl-acetic acid) ethyl ester


Y264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 26








(Iz)




embedded image













and pharmaceutically acceptable salts thereof, wherein:











Compound
Y
R1
(R8)a
(R8)b





Z1 (a and b)
S
—H
—Cl
—H


Z2 (a and b)
S
—H
—Br
—H


Z3 (a and b)
S
—H
—F
—H


Z4 (a and b)
S
—H
—CH3
—H


Z5 (a and b)
S
—H
—CF3
—H


Z6 (a and b)
S
—H
—OCH3
—H


Z7 (a and b)
S
—H
—OCH2CH3
—H


Z8 (a and b)
S
—H
—OCF3
—H


Z9 (a and b)
S
—H
-tert-butyl
—H


Z10 (a and b)
S
—H
-iso-propyl
—H


Z11 (a and b)
S
—H
—CH3
—CH3


Z12 (a and b)
S
—H
—H
—H


Z13 (a and b)
S
—H
—H
—Cl


Z14 (a and b)
S
—H
—H
—Br


Z15 (a and b)
S
—H
—H
—F


Z16 (a and b)
S
—H
—H
—CH3


Z17 (a and b)
S
—H
—H
—CF3


Z18 (a and b)
S
—H
—H
—OCH3


Z19 (a and b)
S
—H
—H
—OCH2CH3


Z20 (a and b)
S
—H
—H
—OCF3


Z21 (a and b)
S
—H
—H
-tert-butyl


Z22 (a and b)
S
—H
—H
-iso-propyl


Z23 (a and b)
S
—Cl
—Cl
—H


Z24 (a and b)
S
—Cl
—Br
—H


Z25 (a and b)
S
—Cl
—F
—H


Z26 (a and b)
S
—Cl
—CH3
—H


Z27 (a and b)
S
—Cl
—CF3
—H


Z28 (a and b)
S
—Cl
—OCH3
—H


Z29 (a and b)
S
—Cl
—OCH2CH3
—H


Z30 (a and b)
S
—Cl
—OCF3
—H


Z31 (a and b)
S
—Cl
-tert-butyl
—H


Z32 (a and b)
S
—Cl
-iso-propyl
—H


Z33 (a and b)
S
—Cl
—CH3
—CH3


Z34 (a and b)
S
—Cl
—H
—H


Z35 (a and b)
S
—Cl
—H
—Cl


Z36 (a and b)
S
—Cl
—H
—Br


Z37 (a and b)
S
—Cl
—H
—F


Z38 (a and b)
S
—Cl
—H
—CH3


Z39 (a and b)
S
—Cl
—H
—CF3


Z40 (a and b)
S
—Cl
—H
—OCH3


Z41 (a and b)
S
—Cl
—H
—OCH2CH3


Z42 (a and b)
S
—Cl
—H
—OCF3


Z43 (a and b)
S
—Cl
—H
-tert-butyl


Z44 (a and b)
S
—Cl
—H
-iso-propyl


Z45 (a and b)
S
—Cl
—H
—OCF3


Z46 (a and b)
S
—Cl
—H
-tert-butyl


Z47 (a and b)
S
—Cl
—H
-iso-propyl


Z48 (a and b)
S
—CH3
—Cl
—H


Z49 (a and b)
S
—CH3
—Br
—H


Z50 (a and b)
S
—CH3
—F
—H


Z51 (a and b)
S
—CH3
—CH3
—H


Z52 (a and b)
S
—CH3
—CF3
—H


Z53 (a and b)
S
—CH3
—OCH3
—H


Z54 (a and b)
S
—CH3
—OCH2CH3
—H


Z55 (a and b)
S
—CH3
—OCF3
—H


Z56 (a and b)
S
—CH3
-tert-butyl
—H


Z57 (a and b)
S
—CH3
-iso-propyl
—H


Z58 (a and b)
S
—CH3
—CH3
—CH3


Z59 (a and b)
S
—CH3
—H
—H


Z60 (a and b)
S
—CH3
—H
—Cl


Z61 (a and b)
S
—CH3
—H
—Br


Z62 (a and b)
S
—CH3
—H
—F


Z63 (a and b)
S
—CH3
—H
—CH3


Z64 (a and b)
S
—CH3
—H
—CF3


Z65 (a and b)
S
—CH3
—H
—OCH3


Z66 (a and b)
S
—CH3
—H
—OCH2CH3


Z67 (a and b)
S
—CH3
—H
—OCF3


Z68 (a and b)
S
—CH3
—H
-tert-butyl


Z69 (a and b)
S
—CH3
—H
-iso-propyl


Z70 (a and b)
S
—CF3
—Cl
—H


Z71 (a and b)
S
—CF3
—Br
—H


Z72 (a and b)
S
—CF3
—F
—H


Z73 (a and b)
S
—CF3
—CH3
—H


Z74 (a and b)
S
—CF3
—CF3
—H


Z75 (a and b)
S
—CF3
—OCH3
—H


Z76 (a and b)
S
—CF3
—OCH2CH3
—H


Z77 (a and b)
S
—CF3
—OCF3
—H


Z78 (a and b)
S
—CF3
-tert-butyl
—H


Z79 (a and b)
S
—CF3
-iso-propyl
—H


Z80 (a and b)
S
—CF3
—CH3
—CH3


Z81 (a and b)
S
—CF3
—H
—H


Z82 (a and b)
S
—CF3
—H
—Cl


Z83 (a and b)
S
—CF3
—H
—Br


Z84 (a and b)
S
—CF3
—H
—F


Z85 (a and b)
S
—CF3
—H
—CH3


Z86 (a and b)
S
—CF3
—H
—CF3


Z87 (a and b)
S
—CF3
—H
—OCH3


Z88 (a and b)
S
—CF3
—H
—OCH2CH3


Z89 (a and b)
S
—CF3
—H
—OCF3


Z90 (a and b)
S
—CF3
—H
-tert-butyl


Z91 (a and b)
S
—CF3
—H
-iso-propyl


Z92 (a and b)
S
—CHF2
—Cl
—H


Z93 (a and b)
S
—CHF2
—Br
—H


Z94 (a and b)
S
—CHF2
—F
—H


Z95 (a and b)
S
—CHF2
—CH3
—H


Z96 (a and b)
S
—CHF2
—CF3
—H


Z97 (a and b)
S
—CHF2
—OCH3
—H


Z98 (a and b)
S
—CHF2
—OCH2CH3
—H


Z99 (a and b)
S
—CHF2
—OCF3
—H


Z100 (a and b)
S
—CHF2
-tert-butyl
—H


Z101 (a and b)
S
—CHF2
-iso-propyl
—H


Z102 (a and b)
S
—CHF2
—CH3
—CH3


Z103 (a and b)
S
—CHF2
—H
—H


Z104 (a and b)
S
—CHF2
—H
—Cl


Z105 (a and b)
S
—CHF2
—H
—Br


Z106 (a and b)
S
—CHF2
—H
—F


Z107 (a and b)
S
—CHF2
—H
—CH3


Z108 (a and b)
S
—CHF2
—H
—CF3


Z109 (a and b)
S
—CHF2
—H
—OCH3


Z110 (a and b)
S
—CHF2
—H
—OCH2CH3


Z111 (a and b)
S
—CHF2
—H
—OCF3


Z112 (a and b)
S
—CHF2
—H
-tert-butyl


Z113 (a and b)
S
—CHF2
—H
-iso-propyl


Z114 (a and b)
S
—OH
—Cl
—H


Z115 (a and b)
S
—OH
—Br
—H


Z116 (a and b)
S
—OH
—F
—H


Z117 (a and b)
S
—OH
—CH3
—H


Z118 (a and b)
S
—OH
—CF3
—H


Z119 (a and b)
S
—OH
—OCH3
—H


Z120 (a and b)
S
—OH
—OCH2CH3
—H


Z121 (a and b)
S
—OH
—OCF3
—H


Z122 (a and b)
S
—OH
-tert-butyl
—H


Z123 (a and b)
S
—OH
-iso-propyl
—H


Z124 (a and b)
S
—OH
—CH3
—CH3


Z125 (a and b)
S
—OH
—H
—H


Z126 (a and b)
S
—OH
—H
—Cl


Z127 (a and b)
S
—OH
—H
—Br


Z128 (a and b)
S
—OH
—H
—F


Z129 (a and b)
S
—OH
—H
—CH3


Z130 (a and b)
S
—OH
—H
—CF3


Z131 (a and b)
S
—OH
—H
—OCH3


Z132 (a and b)
S
—OH
—H
—OCH2CH3


Z133 (a and b)
S
—OH
—H
—OCF3


Z134 (a and b)
S
—OH
—H
-tert-butyl


Z135 (a and b)
S
—OH
—H
-iso-propyl


Z136 (a and b)
S
—NO2
—Cl
—H


Z137 (a and b)
S
—NO2
—Br
—H


Z138 (a and b)
S
—NO2
—F
—H


Z139 (a and b)
S
—NO2
—CH3
—H


Z140 (a and b)
S
—NO2
—CF3
—H


Z141 (a and b)
S
—NO2
—OCH3
—H


Z142 (a and b)
S
—NO2
—OCH2CH3
—H


Z143 (a and b)
S
—NO2
—OCF3
—H


Z144 (a and b)
S
—NO2
-tert-butyl
—H


Z145 (a and b)
S
—NO2
-iso-propyl
—H


Z146 (a and b)
S
—NO2
—CH3
—CH3


Z147 (a and b)
S
—NO2
—H
—H


Z148 (a and b)
S
—NO2
—H
—Cl


Z149 (a and b)
S
—NO2
—H
—Br


Z150 (a and b)
S
—NO2
—H
—F


Z151 (a and b)
S
—NO2
—H
—CH3


Z152 (a and b)
S
—NO2
—H
—CF3


Z153 (a and b)
S
—NO2
—H
—OCH3


Z154 (a and b)
S
—NO2
—H
—OCH2CH3


Z155 (a and b)
S
—NO2
—H
—OCF3


Z156 (a and b)
S
—NO2
—H
-tert-butyl


Z157 (a and b)
S
—NO2
—H
-iso-propyl


Z158 (a and b)
S
—CN
—Br
—H


Z159 (a and b)
S
—CN
—Cl
—H


Z160 (a and b)
S
—CN
—F
—H


Z161 (a and b)
S
—CN
—CH3
—H


Z162 (a and b)
S
—CN
—CF3
—H


Z163 (a and b)
S
—CN
—OCH3
—H


Z164 (a and b)
S
—CN
—OCH2CH3
—H


Z165 (a and b)
S
—CN
—OCF3
—H


Z166 (a and b)
S
—CN
-tert-butyl
—H


Z167 (a and b)
S
—CN
-iso-propyl
—H


Z168 (a and b)
S
—CN
—CH3
—CH3


Z169 (a and b)
S
—CN
—H
—H


Z170 (a and b)
S
—CN
—H
—Cl


Z171 (a and b)
S
—CN
—H
—Br


Z172 (a and b)
S
—CN
—H
—F


Z173 (a and b)
S
—CN
—H
—CH3


Z174 (a and b)
S
—CN
—H
—CF3


Z175 (a and b)
S
—CN
—H
—OCH3


Z176 (a and b)
S
—CN
—H
—OCH2CH3


Z177 (a and b)
S
—CN
—H
—OCF3


Z178 (a and b)
S
—CN
—H
-tert-butyl


Z179 (a and b)
S
—CN
—H
-iso-propyl


Z180 (a and b)
S
—Br
—Br
—H


Z181 (a and b)
S
—Br
—Cl
—H


Z182 (a and b)
S
—Br
—F
—H


Z183 (a and b)
S
—Br
—CH3
—H


Z184 (a and b)
S
—Br
—CF3
—H


Z185 (a and b)
S
—Br
—OCH3
—H


Z186 (a and b)
S
—Br
—OCH2CH3
—H


Z187 (a and b)
S
—Br
—OCF3
—H


Z188 (a and b)
S
—Br
-tert-butyl
—H


Z189 (a and b)
S
—Br
-iso-propyl
—H


Z190 (a and b)
S
—Br
—CH3
—CH3


Z191 (a and b)
S
—Br
—H
—H


Z192 (a and b)
S
—Br
—H
—Cl


Z193 (a and b)
S
—Br
—H
—Br


Z194 (a and b)
S
—Br
—H
—F


Z195 (a and b)
S
—Br
—H
—CH3


Z196 (a and b)
S
—Br
—H
—CF3


Z197 (a and b)
S
—Br
—H
—OCH3


Z198 (a and b)
S
—Br
—H
—OCH2CH3


Z199 (a and b)
S
—Br
—H
—OCF3


Z200 (a and b)
S
—Br
—H
-tert-butyl


Z201 (a and b)
S
—Br
—H
-iso-propyl


Z202 (a and b)
S
—I
—Cl
—H


Z203 (a and b)
S
—I
—Br
—H


Z204 (a and b)
S
—I
—F
—H


Z205 (a and b)
S
—I
—CH3
—H


Z206 (a and b)
S
—I
—CF3
—H


Z207 (a and b)
S
—I
—OCH3
—H


Z208 (a and b)
S
—I
—OCH2CH3
—H


Z209 (a and b)
S
—I
—OCF3
—H


Z210 (a and b)
S
—I
-tert-butyl
—H


Z211 (a and b)
S
—I
-iso-propyl
—H


Z212 (a and b)
S
—I
—CH3
—CH3


Z213 (a and b)
S
—I
—H
—H


Z214 (a and b)
S
—I
—H
—Cl


Z215 (a and b)
S
—I
—H
—Br


Z216 (a and b)
S
—I
—H
—F


Z217 (a and b)
S
—I
—H
—CH3


Z218 (a and b)
S
—I
—H
—CF3


Z219 (a and b)
S
—I
—H
—OCH3


Z220 (a and b)
S
—I
—H
—OCH2CH3


Z221 (a and b)
S
—I
—H
—OCF3


Z222 (a and b)
S
—I
—H
-tert-butyl


Z223 (a and b)
S
—I
—H
-iso-propyl


Z224 (a and b)
O
—H
—Cl
—H


Z225 (a and b)
O
—H
—Br
—H


Z226 (a and b)
O
—H
—F
—H


Z227 (a and b)
O
—H
—CH3
—H


Z228 (a and b)
O
—H
—CF3
—H


Z229 (a and b)
O
—H
—OCH3
—H


Z230 (a and b)
O
—H
—OCH2CH3
—H


Z231 (a and b)
O
—H
—OCF3
—H


Z232 (a and b)
O
—H
-tert-butyl
—H


Z233 (a and b)
O
—H
-iso-propyl
—H


Z234 (a and b)
O
—H
—CH3
—CH3


Z235 (a and b)
O
—H
—H
—H


Z236 (a and b)
O
—H
—H
—Cl


Z237 (a and b)
O
—H
—H
—Br


Z238 (a and b)
O
—H
—H
—F


Z239 (a and b)
O
—H
—H
—CH3


Z240 (a and b)
O
—H
—H
—CF3


Z241 (a and b)
O
—H
—H
—OCH3


Z242 (a and b)
O
—H
—H
—OCH2CH3


Z243 (a and b)
O
—H
—H
—OCF3


Z244 (a and b)
O
—H
—H
-tert-butyl


Z245 (a and b)
O
—H
—H
-iso-propyl


Z246 (a and b)
O
—Cl
—Cl
—H


Z247 (a and b)
O
—Cl
—Br
—H


Z248 (a and b)
O
—Cl
—F
—H


Z249 (a and b)
O
—Cl
—CH3
—H


Z250 (a and b)
O
—Cl
—CF3
—H


Z251 (a and b)
O
—Cl
—OCH3
—H


Z252 (a and b)
O
—Cl
—OCH2CH3
—H


Z253 (a and b)
O
—Cl
—OCF3
—H


Z254 (a and b)
O
—Cl
-tert-butyl
—H


Z255 (a and b)
O
—Cl
-iso-propyl
—H


Z256 (a and b)
O
—Cl
—CH3
—CH3


Z257 (a and b)
O
—Cl
—H
—H


Z258 (a and b)
O
—Cl
—H
—CH3


Z259 (a and b)
O
—Cl
—H
—Cl


Z260 (a and b)
O
—Cl
—H
—Br


Z261 (a and b)
O
—Cl
—H
—F


Z262 (a and b)
O
—Cl
—H
—CF3


Z263 (a and b)
O
—Cl
—H
—OCH3


Z264 (a and b)
O
—Cl
—H
—OCH2CH3


Z265 (a and b)
O
—Cl
—H
—OCF3


Z266 (a and b)
O
—Cl
—H
-tert-butyl


Z267 (a and b)
O
—Cl
—H
-iso-propyl


Z268 (a and b)
O
—Cl
—H
—OCF3


Z269 (a and b)
O
—Cl
—H
-tert-butyl


Z270 (a and b)
O
—Cl
—H
-iso-propyl


Z271 (a and b)
O
—CH3
—Cl
—H


Z272 (a and b)
O
—CH3
—Br
—H


Z273 (a and b)
O
—CH3
—F
—H


Z274 (a and b)
O
—CH3
—CH3
—H


Z275 (a and b)
O
—CH3
—CF3
—H


Z276 (a and b)
O
—CH3
—OCH3
—H


Z277 (a and b)
O
—CH3
—OCH2CH3
—H


Z278 (a and b)
O
—CH3
—OCF3
—H


Z279 (a and b)
O
—CH3
-tert-butyl
—H


Z280 (a and b)
O
—CH3
-iso-propyl
—H


Z281 (a and b)
O
—CH3
—CH3
—CH3


Z282 (a and b)
O
—CH3
—H
—H


Z283 (a and b)
O
—CH3
—H
—Cl


Z284 (a and b)
O
—CH3
—H
—Br


Z285 (a and b)
O
—CH3
—H
—F


Z286 (a and b)
O
—CH3
—H
—CH3


Z287 (a and b)
O
—CH3
—H
—CF3


Z288 (a and b)
O
—CH3
—H
—OCH3


Z289 (a and b)
O
—CH3
—H
—OCH2CH3


Z290 (a and b)
O
—CH3
—H
—OCF3


Z291 (a and b)
O
—CH3
—H
-tert-butyl


Z292 (a and b)
O
—CH3
—H
-iso-propyl


Z293 (a and b)
O
—CF3
—Cl
—H


Z294 (a and b)
O
—CF3
—Br
—H


Z295 (a and b)
O
—CF3
—F
—H


Z296 (a and b)
O
—CF3
—CH3
—H


Z297 (a and b)
O
—CF3
—CF3
—H


Z298 (a and b)
O
—CF3
—OCH3
—H


Z299 (a and b)
O
—CF3
—OCH2CH3
—H


Z300 (a and b)
O
—CF3
—OCF3
—H


Z301 (a and b)
O
—CF3
-tert-butyl
—H


Z302 (a and b)
O
—CF3
-iso-propyl
—H


Z303 (a and b)
O
—CF3
—CH3
—CH3


Z304 (a and b)
O
—CF3
—H
—H


Z305 (a and b)
O
—CF3
—H
—Cl


Z306 (a and b)
O
—CF3
—H
—Br


Z307 (a and b)
O
—CF3
—H
—F


Z308 (a and b)
O
—CF3
—H
—CH3


Z309 (a and b)
O
—CF3
—H
—CF3


Z310 (a and b)
O
—CF3
—H
—OCH3


Z311 (a and b)
O
—CF3
—H
—OCH2CH3


Z312 (a and b)
O
—CF3
—H
—OCF3


Z313 (a and b)
O
—CF3
—H
-tert-butyl


Z314 (a and b)
O
—CF3
—H
-iso-propyl


Z315 (a and b)
O
—CHF2
—Cl
—H


Z316 (a and b)
O
—CHF2
—Br
—H


Z317 (a and b)
O
—CHF2
—F
—H


Z318 (a and b)
O
—CHF2
—CH3
—H


Z319 (a and b)
O
—CHF2
—CF3
—H


Z320 (a and b)
O
—CHF2
—OCH3
—H


Z321 (a and b)
O
—CHF2
—OCH2CH3
—H


Z322 (a and b)
O
—CHF2
—OCF3
—H


Z323 (a and b)
O
—CHF2
-tert-butyl
—H


Z324 (a and b)
O
—CHF2
-iso-propyl
—H


Z325 (a and b)
O
—CHF2
—CH3
—CH3


Z326 (a and b)
O
—CHF2
—H
—H


Z327 (a and b)
O
—CHF2
—H
—Cl


Z328 (a and b)
O
—CHF2
—H
—Br


Z329 (a and b)
O
—CHF2
—H
—F


Z330 (a and b)
O
—CHF2
—H
—CH3


Z331 (a and b)
O
—CHF2
—H
—CF3


Z332 (a and b)
O
—CHF2
—H
—OCH3


Z333 (a and b)
O
—CHF2
—H
—OCH2CH3


Z334 (a and b)
O
—CHF2
—H
—OCF3


Z335 (a and b)
O
—CHF2
—H
-tert-butyl


Z336 (a and b)
O
—CHF2
—H
-iso-propyl


Z337 (a and b)
O
—OH
—Cl
—H


Z338 (a and b)
O
—OH
—Br
—H


Z339 (a and b)
O
—OH
—F
—H


Z340 (a and b)
O
—OH
—CH3
—H


Z341 (a and b)
O
—OH
—CF3
—H


Z342 (a and b)
O
—OH
—OCH3
—H


Z343 (a and b)
O
—OH
—OCH2CH3
—H


Z344 (a and b)
O
—OH
—OCF3
—H


Z345 (a and b)
O
—OH
-tert-butyl
—H


Z346 (a and b)
O
—OH
-iso-propyl
—H


Z347 (a and b)
O
—OH
—CH3
—CH3


Z348 (a and b)
O
—OH
—H
—H


Z349 (a and b)
O
—OH
—H
—Cl


Z350 (a and b)
O
—OH
—H
—Br


Z351 (a and b)
O
—OH
—H
—F


Z352 (a and b)
O
—OH
—H
—CH3


Z353 (a and b)
O
—OH
—H
—CF3


Z354 (a and b)
O
—OH
—H
—OCH3


Z355 (a and b)
O
—OH
—H
—OCH2CH3


Z356 (a and b)
O
—OH
—H
—OCF3


Z357 (a and b)
O
—OH
—H
-tert-butyl


Z358 (a and b)
O
—OH
—H
-iso-propyl


Z359 (a and b)
O
—NO2
—Cl
—H


Z360 (a and b)
O
—NO2
—Br
—H


Z361 (a and b)
O
—NO2
—F
—H


Z362 (a and b)
O
—NO2
—CH3
—H


Z363 (a and b)
O
—NO2
—CF3
—H


Z364 (a and b)
O
—NO2
—OCH3
—H


Z365 (a and b)
O
—NO2
—OCH2CH3
—H


Z366 (a and b)
O
—NO2
—OCF3
—H


Z367 (a and b)
O
—NO2
-tert-butyl
—H


Z368 (a and b)
O
—NO2
-iso-propyl
—H


Z369 (a and b)
O
—NO2
—CH3
—CH3


Z370 (a and b)
O
—NO2
—H
—H


Z371 (a and b)
O
—NO2
—H
—Cl


Z372 (a and b)
O
—NO2
—H
—Br


Z373 (a and b)
O
—NO2
—H
—F


Z374 (a and b)
O
—NO2
—H
—CH3


Z375 (a and b)
O
—NO2
—H
—CF3


Z376 (a and b)
O
—NO2
—H
—OCH3


Z377 (a and b)
O
—NO2
—H
—OCH2CH3


Z378 (a and b)
O
—NO2
—H
—OCF3


Z379 (a and b)
O
—NO2
—H
-tert-butyl


Z380 (a and b)
O
—NO2
—H
-iso-propyl


Z381 (a and b)
O
—CN
—Br
—H


Z382 (a and b)
O
—CN
—Cl
—H


Z383 (a and b)
O
—CN
—F
—H


Z384 (a and b)
O
—CN
—CH3
—H


Z385 (a and b)
O
—CN
—CF3
—H


Z386 (a and b)
O
—CN
—OCH3
—H


Z387 (a and b)
O
—CN
—OCH2CH3
—H


Z388 (a and b)
O
—CN
—OCF3
—H


Z389 (a and b)
O
—CN
-tert-butyl
—H


Z390 (a and b)
O
—CN
-iso-propyl
—H


Z391 (a and b)
O
—CN
—CH3
—CH3


Z392 (a and b)
O
—CN
—H
—H


Z393 (a and b)
O
—CN
—H
—Cl


Z394 (a and b)
O
—CN
—H
—Br


Z395 (a and b)
O
—CN
—H
—F


Z396 (a and b)
O
—CN
—H
—CH3


Z397 (a and b)
O
—CN
—H
—CF3


Z398 (a and b)
O
—CN
—H
—OCH3


Z399 (a and b)
O
—CN
—H
—OCH2CH3


Z400 (a and b)
O
—CN
—H
—OCF3


Z401 (a and b)
O
—CN
—H
-tert-butyl


Z402 (a and b)
O
—CN
—H
-iso-propyl


Z403 (a and b)
O
—Br
—Br
—H


Z404 (a and b)
O
—Br
—Cl
—H


Z405 (a and b)
O
—Br
—F
—H


Z406 (a and b)
O
—Br
—CH3
—H


Z407 (a and b)
O
—Br
—CF3
—H


Z408 (a and b)
O
—Br
—OCH3
—H


Z409 (a and b)
O
—Br
—OCH2CH3
—H


Z410 (a and b)
O
—Br
—OCF3
—H


Z411 (a and b)
O
—Br
-tert-butyl
—H


Z412 (a and b)
O
—Br
-iso-propyl
—H


Z413 (a and b)
O
—Br
—CH3
—CH3


Z414 (a and b)
O
—Br
—H
—H


Z415 (a and b)
O
—Br
—H
—Cl


Z416 (a and b)
O
—Br
—H
—Br


Z417 (a and b)
O
—Br
—H
—F


Z418 (a and b)
O
—Br
—H
—CH3


Z419 (a and b)
O
—Br
—H
—CF3


Z420 (a and b)
O
—Br
—H
—OCH3


Z421 (a and b)
O
—Br
—H
—OCH2CH3


Z422 (a and b)
O
—Br
—H
—OCF3


Z423 (a and b)
O
—Br
—H
-tert-butyl


Z424 (a and b)
O
—Br
—H
-iso-propyl


Z425 (a and b)
O
—I
—Cl
—H


Z426 (a and b)
O
—I
—Br
—H


Z427 (a and b)
O
—I
—F
—H


Z428 (a and b)
O
—I
—CH3
—H


Z429 (a and b)
O
—I
—CF3
—H


Z430 (a and b)
O
—I
—OCH3
—H


Z431 (a and b)
O
—I
—OCH2CH3
—H


Z432 (a and b)
O
—I
—OCF3
—H


Z433 (a and b)
O
—I
-tert-butyl
—H


Z434 (a and b)
O
—I
-iso-propyl
—H


Z435 (a and b)
O
—I
—CH3
—CH3


Z436 (a and b)
O
—I
—H
—H


Z437 (a and b)
O
—I
—H
—Cl


Z438 (a and b)
O
—I
—H
—Br


Z439 (a and b)
O
—I
—H
—F


Z440 (a and b)
O
—I
—H
—CH3


Z441 (a and b)
O
—I
—H
—CF3


Z442 (a and b)
O
—I
—H
—OCH3


Z443 (a and b)
O
—I
—H
—OCH2CH3


Z444 (a and b)
O
—I
—H
—OCF3


Z445 (a and b)
O
—I
—H
-tert-butyl


Z446 (a and b)
O
—I
—H
-iso-propyl


Z447 (a and b)
NH
—H
—Cl
—H


Z448 (a and b)
NH
—H
—Br
—H


Z449 (a and b)
NH
—H
—F
—H


Z450 (a and b)
NH
—H
—CH3
—H


Z451 (a and b)
NH
—H
—CF3
—H


Z452 (a and b)
NH
—H
—OCH3
—H


Z453 (a and b)
NH
—H
—OCH2CH3
—H


Z454 (a and b)
NH
—H
—OCF3
—H


Z455 (a and b)
NH
—H
-tert-butyl
—H


Z456 (a and b)
NH
—H
-iso-propyl
—H


Z457 (a and b)
NH
—H
—CH3
—CH3


Z458 (a and b)
NH
—H
—H
—H


Z459 (a and b)
NH
—H
—H
—Cl


Z460 (a and b)
NH
—H
—H
—Br


Z461 (a and b)
NH
—H
—H
—F


Z462 (a and b)
NH
—H
—H
—CH3


Z463 (a and b)
NH
—H
—H
—CF3


Z464 (a and b)
NH
—H
—H
—OCH3


Z465 (a and b)
NH
—H
—H
—OCH2CH3


Z466 (a and b)
NH
—H
—H
—OCF3


Z467 (a and b)
NH
—H
—H
-tert-butyl


Z468 (a and b)
NH
—H
—H
-iso-propyl


Z469 (a and b)
NH
—Cl
—Cl
—H


Z470 (a and b)
NH
—Cl
—Br
—H


Z471 (a and b)
NH
—Cl
—F
—H


Z472 (a and b)
NH
—Cl
—CH3
—H


Z473 (a and b)
NH
—Cl
—CF3
—H


Z474 (a and b)
NH
—Cl
—OCH3
—H


Z475 (a and b)
NH
—Cl
—OCH2CH3
—H


Z476 (a and b)
NH
—Cl
—OCF3
—H


Z477 (a and b)
NH
—Cl
-tert-butyl
—H


Z478 (a and b)
NH
—Cl
-iso-propyl
—H


Z479 (a and b)
NH
—Cl
—CH3
—CH3


Z480 (a and b)
NH
—Cl
—H
—H


Z481 (a and b)
NH
—Cl
—H
—CH3


Z482 (a and b)
NH
—Cl
—H
—Cl


Z483 (a and b)
NH
—Cl
—H
—Br


Z484 (a and b)
NH
—Cl
—H
—F


Z485 (a and b)
NH
—Cl
—H
—CF3


Z486 (a and b)
NH
—Cl
—H
—OCH3


Z487 (a and b)
NH
—Cl
—H
—OCH2CH3


Z488 (a and b)
NH
—Cl
—H
—OCF3


Z489 (a and b)
NH
—Cl
—H
-tert-butyl


Z490 (a and b)
NH
—Cl
—H
-iso-propyl


Z491 (a and b)
NH
—Cl
—H
—OCF3


Z492 (a and b)
NH
—Cl
—H
-tert-butyl


Z493 (a and b)
NH
—Cl
—H
-iso-propyl


Z494 (a and b)
NH
—CH3
—Cl
—H


Z495 (a and b)
NH
—CH3
—Br
—H


Z496 (a and b)
NH
—CH3
—F
—H


Z497 (a and b)
NH
—CH3
—CH3
—H


Z498 (a and b)
NH
—CH3
—CF3
—H


Z499 (a and b)
NH
—CH3
—OCH3
—H


Z500 (a and b)
NH
—CH3
—OCH2CH3
—H


Z501 (a and b)
NH
—CH3
—OCF3
—H


Z502 (a and b)
NH
—CH3
-tert-butyl
—H


Z503 (a and b)
NH
—CH3
-iso-propyl
—H


Z504 (a and b)
NH
—CH3
—CH3
—CH3


Z505 (a and b)
NH
—CH3
—H
—H


Z506 (a and b)
NH
—CH3
—H
—Cl


Z507 (a and b)
NH
—CH3
—H
—Br


Z508 (a and b)
NH
—CH3
—H
—F


Z509 (a and b)
NH
—CH3
—H
—CH3


Z510 (a and b)
NH
—CH3
—H
—CF3


Z511 (a and b)
NH
—CH3
—H
—OCH3


Z512 (a and b)
NH
—CH3
—H
—OCH2CH3


Z513 (a and b)
NH
—CH3
—H
—OCF3


Z514 (a and b)
NH
—CH3
—H
-tert-butyl


Z515 (a and b)
NH
—CH3
—H
-iso-propyl


Z516 (a and b)
NH
—CF3
—Cl
—H


Z517 (a and b)
NH
—CF3
—Br
—H


Z518 (a and b)
NH
—CF3
—F
—H


Z519 (a and b)
NH
—CF3
—CH3
—H


Z520 (a and b)
NH
—CF3
—CF3
—H


Z521 (a and b)
NH
—CF3
—OCH3
—H


Z522 (a and b)
NH
—CF3
—OCH2CH3
—H


Z523 (a and b)
NH
—CF3
—OCF3
—H


Z524 (a and b)
NH
—CF3
-tert-butyl
—H


Z525 (a and b)
NH
—CF3
-iso-propyl
—H


Z526 (a and b)
NH
—CF3
—CH3
—CH3


Z527 (a and b)
NH
—CF3
—H
—H


Z528 (a and b)
NH
—CF3
—H
—Cl


Z529 (a and b)
NH
—CF3
—H
—Br


Z530 (a and b)
NH
—CF3
—H
—F


Z531 (a and b)
NH
—CF3
—H
—CH3


Z532 (a and b)
NH
—CF3
—H
—CF3


Z533 (a and b)
NH
—CF3
—H
—OCH3


Z534 (a and b)
NH
—CF3
—H
—OCH2CH3


Z535 (a and b)
NH
—CF3
—H
—OCF3


Z536 (a and b)
NH
—CF3
—H
-tert-butyl


Z537 (a and b)
NH
—CF3
—H
-iso-propyl


Z538 (a and b)
NH
—CHF2
—Cl
—H


Z539 (a and b)
NH
—CHF2
—Br
—H


Z540 (a and b)
NH
—CHF2
—F
—H


Z541 (a and b)
NH
—CHF2
—CH3
—H


Z542 (a and b)
NH
—CHF2
—CF3
—H


Z543 (a and b)
NH
—CHF2
—OCH3
—H


Z544 (a and b)
NH
—CHF2
—OCH2CH3
—H


Z545 (a and b)
NH
—CHF2
—OCF3
—H


Z546 (a and b)
NH
—CHF2
-tert-butyl
—H


Z547 (a and b)
NH
—CHF2
-iso-propyl
—H


Z548 (a and b)
NH
—CHF2
—CH3
—CH3


Z549 (a and b)
NH
—CHF2
—H
—H


Z550 (a and b)
NH
—CHF2
—H
—Cl


Z551 (a and b)
NH
—CHF2
—H
—Br


Z552 (a and b)
NH
—CHF2
—H
—F


Z553 (a and b)
NH
—CHF2
—H
—CH3


Z554 (a and b)
NH
—CHF2
—H
—CF3


Z555 (a and b)
NH
—CHF2
—H
—OCH3


Z556 (a and b)
NH
—CHF2
—H
—OCH2CH3


Z557 (a and b)
NH
—CHF2
—H
—OCF3


Z558 (a and b)
NH
—CHF2
—H
-tert-butyl


Z559 (a and b)
NH
—CHF2
—H
-iso-propyl


Z560 (a and b)
NH
—OH
—Cl
—H


Z561 (a and b)
NH
—OH
—Br
—H


Z562 (a and b)
NH
—OH
—F
—H


Z563 (a and b)
NH
—OH
—CH3
—H


Z564 (a and b)
NH
—OH
—CF3
—H


Z565 (a and b)
NH
—OH
—OCH3
—H


Z566 (a and b)
NH
—OH
—OCH2CH3
—H


Z567 (a and b)
NH
—OH
—OCF3
—H


Z568 (a and b)
NH
—OH
-tert-butyl
—H


Z569 (a and b)
NH
—OH
-iso-propyl
—H


Z570 (a and b)
NH
—OH
—CH3
—CH3


Z571 (a and b)
NH
—OH
—H
—H


Z572 (a and b)
NH
—OH
—H
—Cl


Z573 (a and b)
NH
—OH
—H
—Br


Z574 (a and b)
NH
—OH
—H
—F


Z575 (a and b)
NH
—OH
—H
—CH3


Z576 (a and b)
NH
—OH
—H
—CF3


Z577 (a and b)
NH
—OH
—H
—OCH3


Z578 (a and b)
NH
—OH
—H
—OCH2CH3


Z579 (a and b)
NH
—OH
—H
—OCF3


Z580 (a and b)
NH
—OH
—H
-tert-butyl


Z581 (a and b)
NH
—OH
—H
-iso-propyl


Z582 (a and b)
NH
—NO2
—Cl
—H


Z583 (a and b)
NH
—NO2
—Br
—H


Z584 (a and b)
NH
—NO2
—F
—H


Z585 (a and b)
NH
—NO2
—CH3
—H


Z586 (a and b)
NH
—NO2
—CF3
—H


Z587 (a and b)
NH
—NO2
—OCH3
—H


Z588 (a and b)
NH
—NO2
—OCH2CH3
—H


Z589 (a and b)
NH
—NO2
—OCF3
—H


Z590 (a and b)
NH
—NO2
-tert-butyl
—H


Z591 (a and b)
NH
—NO2
-iso-propyl
—H


Z592 (a and b)
NH
—NO2
—CH3
—CH3


Z593 (a and b)
NH
—NO2
—H
—H


Z594 (a and b)
NH
—NO2
—H
—Cl


Z595 (a and b)
NH
—NO2
—H
—Br


Z596 (a and b)
NH
—NO2
—H
—F


Z597 (a and b)
NH
—NO2
—H
—CH3


Z598 (a and b)
NH
—NO2
—H
—CF3


Z599 (a and b)
NH
—NO2
—H
—OCH3


Z600 (a and b)
NH
—NO2
—H
—OCH2CH3


Z601 (a and b)
NH
—NO2
—H
—OCF3


Z602 (a and b)
NH
—NO2
—H
-tert-butyl


Z603 (a and b)
NH
—NO2
—H
-iso-propyl


Z604 (a and b)
NH
—CN
—Br
—H


Z605 (a and b)
NH
—CN
—Cl
—H


Z606 (a and b)
NH
—CN
—F
—H


Z607 (a and b)
NH
—CN
—CH3
—H


Z608 (a and b)
NH
—CN
—CF3
—H


Z609 (a and b)
NH
—CN
—OCH3
—H


Z610 (a and b)
NH
—CN
—OCH2CH3
—H


Z611 (a and b)
NH
—CN
—OCF3
—H


Z612 (a and b)
NH
—CN
-tert-butyl
—H


Z613 (a and b)
NH
—CN
-iso-propyl
—H


Z614 (a and b)
NH
—CN
—CH3
—CH3


Z615 (a and b)
NH
—CN
—H
—H


Z616 (a and b)
NH
—CN
—H
—Cl


Z617 (a and b)
NH
—CN
—H
—Br


Z618 (a and b)
NH
—CN
—H
—F


Z619 (a and b)
NH
—CN
—H
—CH3


Z620 (a and b)
NH
—CN
—H
—CF3


Z621 (a and b)
NH
—CN
—H
—OCH3


Z622 (a and b)
NH
—CN
—H
—OCH2CH3


Z623 (a and b)
NH
—CN
—H
—OCF3


Z624 (a and b)
NH
—CN
—H
-tert-butyl


Z625 (a and b)
NH
—CN
—H
-iso-propyl


Z626 (a and b)
NH
—Br
—Br
—H


Z627 (a and b)
NH
—Br
—Cl
—H


Z628 (a and b)
NH
—Br
—F
—H


Z629 (a and b)
NH
—Br
—CH3
—H


Z630 (a and b)
NH
—Br
—CF3
—H


Z631 (a and b)
NH
—Br
—OCH3
—H


Z632 (a and b)
NH
—Br
—OCH2CH3
—H


Z633 (a and b)
NH
—Br
—OCF3
—H


Z634 (a and b)
NH
—Br
-tert-butyl
—H


Z635 (a and b)
NH
—Br
-iso-propyl
—H


Z636 (a and b)
NH
—Br
—CH3
—CH3


Z637 (a and b)
NH
—Br
—H
—H


Z638 (a and b)
NH
—Br
—H
—Cl


Z639 (a and b)
NH
—Br
—H
—Br


Z640 (a and b)
NH
—Br
—H
—F


Z641 (a and b)
NH
—Br
—H
—CH3


Z642 (a and b)
NH
—Br
—H
—CF3


Z643 (a and b)
NH
—Br
—H
—OCH3


Z644 (a and b)
NH
—Br
—H
—OCH2CH3


Z645 (a and b)
NH
—Br
—H
—OCF3


Z646 (a and b)
NH
—Br
—H
-tert-butyl


Z647 (a and b)
NH
—Br
—H
-iso-propyl


Z648 (a and b)
NH
—I
—Cl
—H


Z649 (a and b)
NH
—I
—Br
—H


Z650 (a and b)
NH
—I
—F
—H


Z651 (a and b)
NH
—I
—CH3
—H


Z652 (a and b)
NH
—I
—CF3
—H


Z653 (a and b)
NH
—I
—OCH3
—H


Z654 (a and b)
NH
—I
—OCH2CH3
—H


Z655 (a and b)
NH
—I
—OCF3
—H


Z656 (a and b)
NH
—I
-tert-butyl
—H


Z657 (a and b)
NH
—I
-iso-propyl
—H


Z658 (a and b)
NH
—I
—CH3
—CH3


Z659 (a and b)
NH
—I
—H
—H


Z660 (a and b)
NH
—I
—H
—Cl


Z661 (a and b)
NH
—I
—H
—Br


Z662 (a and b)
NH
—I
—H
—F


Z663 (a and b)
NH
—I
—H
—CH3


Z664 (a and b)
NH
—I
—H
—CF3


Z665 (a and b)
NH
—I
—H
—OCH3


Z666 (a and b)
NH
—I
—H
—OCH2CH3


Z667 (a and b)
NH
—I
—H
—OCF3


Z668 (a and b)
NH
—I
—H
-tert-butyl


Z669 (a and b)
NH
—I
—H
-iso-propyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.














TABLE 27








(Iaa)




embedded image













and pharmaceutically acceptable salts thereof, wherein:









Compound
R1
R8a





AA1 (a and b)
—H
—H


AA2 (a and b)
—H
-tert-butyl


AA3 (a and b)
—H
-iso-butyl


AA4 (a and b)
—H
-sec-butyl


AA5 (a and b)
—H
-iso-propyl


AA6 (a and b)
—H
-n-propyl


AA7 (a and b)
—H
-cyclohexyl


AA8 (a and b)
—H
-tert-butoxy


AA9 (a and b)
—H
-isopropoxy


AA10 (a and b)
—H
—CF3


AA11 (a and b)
—H
—CH2CF3


AA12 (a and b)
—H
—OCF3


AA13 (a and b)
—H
—Cl


AA14 (a and b)
—H
—Br


AA15 (a and b)
—H
—I


AA16 (a and b)
—H
-n-butyl


AA17 (a and b)
—H
—CH3


AA18 (a and b)
—H
—SCF3


AA19 (a and b)
—H
—N(CH2CH3)2


AA20 (a and b)
—H
—OCF2CHF2


AA21 (a and b)
—H
—C(OH)(CF3)2


AA22 (a and b)
—H
-(1,1-dimethyl-pentyl)


AA23 (a and b)
—H
-(1,1-dimethyl-acetic acid) ethyl ester


AA24 (a and b)
—H
—N-piperidinyl


AA25 (a and b)
—Cl
—H


AA26 (a and b)
—Cl
-tert-butyl


AA27 (a and b)
—Cl
-iso-butyl


AA28 (a and b)
—Cl
-sec-butyl


AA29 (a and b)
—Cl
-iso-propyl


AA30 (a and b)
—Cl
-n-propyl


AA31 (a and b)
—Cl
-cyclohexyl


AA32 (a and b)
—Cl
-tert-butoxy


AA33 (a and b)
—Cl
-isopropoxy


AA34 (a and b)
—Cl
—CF3


AA35 (a and b)
—Cl
—CH2CF3


AA36 (a and b)
—Cl
—OCF3


AA37 (a and b)
—Cl
—Cl


AA38 (a and b)
—Cl
—Br


AA39 (a and b)
—Cl
—I


AA40 (a and b)
—Cl
-n-butyl


AA41 (a and b)
—Cl
—CH3


AA42 (a and b)
—Cl
—SCF3


AA43 (a and b)
—Cl
—N(CH2CH3)2


AA44 (a and b)
—Cl
—OCF2CHF2


AA45 (a and b)
—Cl
—C(OH)(CF3)2


AA46 (a and b)
—Cl
-(1,1-dimethyl-pentyl)


AA47 (a and b)
—Cl
-(1,1-dimethyl-acetic acid) ethyl ester


AA48 (a and b)
—Cl
—N-piperidinyl


AA49 (a and b)
—F
—H


AA50 (a and b)
—F
-tert-butyl


AA51 (a and b)
—F
-iso-butyl


AA52 (a and b)
—F
-sec-butyl


AA53 (a and b)
—F
-iso-propyl


AA54 (a and b)
—F
-n-propyl


AA55 (a and b)
—F
-cyclohexyl


AA56 (a and b)
—F
-tert-butoxy


AA57 (a and b)
—F
-isopropoxy


AA58 (a and b)
—F
—CF3


AA59 (a and b)
—F
—CH2CF3


AA60 (a and b)
—F
—OCF3


AA61 (a and b)
—F
—Cl


AA62 (a and b)
—F
—Br


AA63 (a and b)
—F
—I


AA64 (a and b)
—F
-n-butyl


AA65 (a and b)
—F
—CH3


AA66 (a and b)
—F
—SCF3


AA67 (a and b)
—F
—N(CH2CH3)2


AA68 (a and b)
—F
—OCF2CHF2


AA69 (a and b)
—F
—C(OH)(CF3)2


AA70 (a and b)
—F
-(1,1-dimethyl-pentyl)


AA71 (a and b)
—F
-(1,1-dimethyl-acetic acid) ethyl ester


AA72 (a and b)
—F
—N-piperidinyl


AA73 (a and b)
—CH3
—H


AA74 (a and b)
—CH3
-iso-butyl


AA75 (a and b)
—CH3
-tert-butyl


AA76 (a and b)
—CH3
-sec-butyl


AA77 (a and b)
—CH3
-iso-propyl


AA78 (a and b)
—CH3
-n-propyl


AA79 (a and b)
—CH3
-cyclohexyl


AA80 (a and b)
—CH3
-tert-butoxy


AA81 (a and b)
—CH3
-isopropoxy


AA82 (a and b)
—CH3
—CF3


AA83 (a and b)
—CH3
—CH2CF3


AA84 (a and b)
—CH3
—OCF3


AA85 (a and b)
—CH3
—Cl


AA86 (a and b)
—CH3
—Br


AA87 (a and b)
—CH3
—I


AA88 (a and b)
—CH3
-n-butyl


AA89 (a and b)
—CH3
—CH3


AA90 (a and b)
—CH3
—SCF3


AA91 (a and b)
—CH3
—N(CH2CH3)2


AA92 (a and b)
—CH3
—OCF2CHF2


AA93 (a and b)
—CH3
—C(OH)(CF3)2


AA94 (a and b)
—CH3
-(1,1-dimethyl-pentyl)


AA95 (a and b)
—CH3
-(1,1-dimethyl-acetic acid) ethyl ester


AA96 (a and b)
—CH3
—N-piperidinyl


AA97 (a and b)
—CF3
—H


AA98 (a and b)
—CF3
-tert-butyl


AA99 (a and b)
—CF3
-iso-butyl


AA100 (a and b)
—CF3
-sec-butyl


AA101 (a and b)
—CF3
-iso-propyl


AA102 (a and b)
—CF3
-n-propyl


AA103 (a and b)
—CF3
-cyclohexyl


AA104 (a and b)
—CF3
-tert-butoxy


AA105 (a and b)
—CF3
-isopropoxy


AA106 (a and b)
—CF3
—CF3


AA107 (a and b)
—CF3
—CH2CF3


AA108 (a and b)
—CF3
—OCF3


AA109 (a and b)
—CF3
—Cl


AA110 (a and b)
—CF3
—Br


AA111 (a and b)
—CF3
—I


AA112 (a and b)
—CF3
-n-butyl


AA113 (a and b)
—CF3
—CH3


AA114 (a and b)
—CF3
—SCF3


AA115 (a and b)
—CF3
—N(CH2CH3)2


AA116 (a and b)
—CF3
—OCF2CHF2


AA117 (a and b)
—CF3
—C(OH)(CF3)2


AA118 (a and b)
—CF3
-(1,1-dimethyl-pentyl)


AA119 (a and b)
—CF3
-(1,1-dimethyl-acetic acid) ethyl ester


AA120 (a and b)
—CF3
—N-piperidinyl


AA121 (a and b)
—CHF2
-tert-butyl


AA122 (a and b)
—CHF2
—H


AA123 (a and b)
—CHF2
-iso-butyl


AA124 (a and b)
—CHF2
-sec-butyl


AA125 (a and b)
—CHF2
-iso-propyl


AA126 (a and b)
—CHF2
-n-propyl


AA127 (a and b)
—CHF2
-cyclohexyl


AA128 (a and b)
—CHF2
-tert-butoxy


AA129 (a and b)
—CHF2
-isopropoxy


AA130 (a and b)
—CHF2
—CF3


AA131 (a and b)
—CHF2
—CH2CF3


AA132 (a and b)
—CHF2
—OCF3


AA133 (a and b)
—CHF2
—Cl


AA134 (a and b)
—CHF2
—Br


AA135 (a and b)
—CHF2
—I


AA136 (a and b)
—CHF2
-n-butyl


AA137 (a and b)
—CHF2
—CH3


AA138 (a and b)
—CHF2
—SCF3


AA139 (a and b)
—CHF2
—N(CH2CH3)2


AA140 (a and b)
—CHF2
—OCF2CHF2


AA141 (a and b)
—CHF2
—C(OH)(CF3)2


AA142 (a and b)
—CHF2
-(1,1-dimethyl-pentyl)


AA143 (a and b)
—CHF2
-(1,1-dimethyl-acetic acid) ethyl ester


AA144 (a and b)
—CHF2
—N-piperidinyl


AA145 (a and b)
—OH
—H


AA146 (a and b)
—OH
-tert-butyl


AA147 (a and b)
—OH
-iso-butyl


AA148 (a and b)
—OH
-sec-butyl


AA149 (a and b)
—OH
-iso-propyl


AA150 (a and b)
—OH
-n-propyl


AA151 (a and b)
—OH
-cyclohexyl


AA152 (a and b)
—OH
-tert-butoxy


AA153 (a and b)
—OH
-isopropoxy


AA154 (a and b)
—OH
—CF3


AA155 (a and b)
—OH
—CH2CF3


AA156 (a and b)
—OH
—OCF3


AA157 (a and b)
—OH
—Cl


AA158 (a and b)
—OH
—Br


AA159 (a and b)
—OH
—I


AA160 (a and b)
—OH
-n-butyl


AA161 (a and b)
—OH
—CH3


AA162 (a and b)
—OH
—SCF3


AA163 (a and b)
—OH
—N(CH2CH3)2


AA164 (a and b)
—OH
—OCF2CHF2


AA165 (a and b)
—OH
—C(OH)(CF3)2


AA166 (a and b)
—OH
-(1,1-dimethyl-pentyl)


AA167 (a and b)
—OH
-(1,1-dimethyl-acetic acid) ethyl ester


AA168 (a and b)
—OH
—N-piperidinyl


AA169 (a and b)
—NO2
—H


AA170 (a and b)
—NO2
-tert-butyl


AA171 (a and b)
—NO2
-iso-butyl


AA172 (a and b)
—NO2
-sec-butyl


AA173 (a and b)
—NO2
-iso-propyl


AA174 (a and b)
—NO2
-n-propyl


AA175 (a and b)
—NO2
-cyclohexyl


AA176 (a and b)
—NO2
-tert-butoxy


AA177 (a and b)
—NO2
-isopropoxy


AA178 (a and b)
—NO2
—CF3


AA179 (a and b)
—NO2
—CH2CF3


AA180 (a and b)
—NO2
—OCF3


AA181 (a and b)
—NO2
—Cl


AA182 (a and b)
—NO2
—Br


AA183 (a and b)
—NO2
—I


AA184 (a and b)
—NO2
-n-butyl


AA185 (a and b)
—NO2
—CH3


AA186 (a and b)
—NO2
—SCF3


AA187 (a and b)
—NO2
—N(CH2CH3)2


AA188 (a and b)
—NO2
—OCF2CHF2


AA189 (a and b)
—NO2
—C(OH)(CF3)2


AA190 (a and b)
—NO2
-(1,1-dimethyl-pentyl)


AA191 (a and b)
—NO2
-(1,1-dimethyl-acetic acid) ethyl ester


AA192 (a and b)
—NO2
—N-piperidinyl


AA193 (a and b)
—CN
—H


AA194 (a and b)
—CN
-tert-butyl


AA195 (a and b)
—CN
-iso-butyl


AA196 (a and b)
—CN
-sec-butyl


AA197 (a and b)
—CN
-iso-propyl


AA198 (a and b)
—CN
-n-propyl


AA199 (a and b)
—CN
-cyclohexyl


AA200 (a and b)
—CN
-tert-butoxy


AA201 (a and b)
—CN
-isopropoxy


AA202 (a and b)
—CN
—CF3


AA203 (a and b)
—CN
—CH2CF3


AA204 (a and b)
—CN
—OCF3


AA205 (a and b)
—CN
—Cl


AA206 (a and b)
—CN
—Br


AA207 (a and b)
—CN
—I


AA208 (a and b)
—CN
-n-butyl


AA209 (a and b)
—CN
—CH3


AA210 (a and b)
—CN
—SCF3


AA211 (a and b)
—CN
—N(CH2CH3)2


AA212 (a and b)
—CN
—OCF2CHF2


AA213 (a and b)
—CN
—C(OH)(CF3)2


AA214 (a and b)
—CN
-(1,1-dimethyl-pentyl)


AA215 (a and b)
—CN
-(1,1-dimethyl-acetic acid) ethyl ester


AA216 (a and b)
—CN
—N-piperidinyl


AA217 (a and b)
—Br
—H


AA218 (a and b)
—Br
-tert-butyl


AA219 (a and b)
—Br
-iso-butyl


AA220 (a and b)
—Br
-sec-butyl


AA221 (a and b)
—Br
-iso-propyl


AA222 (a and b)
—Br
-n-propyl


AA223 (a and b)
—Br
-cyclohexyl


AA224 (a and b)
—Br
-tert-butoxy


AA225 (a and b)
—Br
-isopropoxy


AA226 (a and b)
—Br
—CF3


AA227 (a and b)
—Br
—CH2CF3


AA228 (a and b)
—Br
—OCF3


AA229 (a and b)
—Br
—Cl


AA230 (a and b)
—Br
—Br


AA231 (a and b)
—Br
—I


AA232 (a and b)
—Br
-n-butyl


AA233 (a and b)
—Br
—CH3


AA234 (a and b)
—Br
—SCF3


AA235 (a and b)
—Br
—N(CH2CH3)2


AA236 (a and b)
—Br
—OCF2CHF2


AA237 (a and b)
—Br
—C(OH)(CF3)2


AA238 (a and b)
—Br
-(1,1-dimethyl-pentyl)


AA239 (a and b)
—Br
-(1,1-dimethyl-acetic acid) ethyl ester


AA240 (a and b)
—Br
—N-piperidinyl


AA241 (a and b)
—I
-tert-butyl


AA242 (a and b)
—I
—H


AA243 (a and b)
—I
-iso-butyl


AA244 (a and b)
—I
-sec-butyl


AA245 (a and b)
—I
-iso-propyl


AA246 (a and b)
—I
-n-propyl


AA247 (a and b)
—I
-cyclohexyl


AA248 (a and b)
—I
-tert-butoxy


AA249 (a and b)
—I
-isopropoxy


AA250 (a and b)
—I
—CF3


AA251 (a and b)
—I
—CH2CF3


AA252 (a and b)
—I
—OCF3


AA253 (a and b)
—I
—Cl


AA254 (a and b)
—I
—Br


AA255 (a and b)
—I
—I


AA256 (a and b)
—I
-n-butyl


AA257 (a and b)
—I
—CH3


AA258 (a and b)
—I
—SCF3


AA259 (a and b)
—I
—N(CH2CH3)2


AA260 (a and b)
—I
—OCF2CHF2


AA261 (a and b)
—I
—C(OH)(CF3)2


AA262 (a and b)
—I
-(1,1-dimethyl-pentyl)


AA263 (a and b)
—I
-(1,1-dimethyl-acetic acid) ethyl ester


AA264 (a and b)
—I
—N-piperidinyl





(a) means that R3 is —H.


(b) means that R3 is —CH3.






4.2 Definitions

As used in connection with the Cyclo(hetero)alkenyl Compounds herein, the terms used above having following meaning:


“—(C1-C10)alkyl” means a straight chain or branched non-cyclic hydrocarbon having from 1 to 10 carbon atoms. Representative straight chain —(C1-C10)alkyls include -methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl, -n-hexyl, -n-heptyl, -n-octyl, -n-nonyl, and -n-decyl. Representative branched —(C1-C10)alkyls include -iso-propyl, -sec-butyl, -iso-butyl, -tert-butyl, -iso-pentyl, -neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1,2-dimethylpentyl, 1,3-dimethylpentyl, 1,2-dimethylhexyl, 1,3-dimethylhexyl, 3,3-dimethylhexyl, 1,2-dimethylheptyl, 1,3-dimethylheptyl, and 3,3-dimethylheptyl.


“—(C1-C6)alkyl” means a straight chain or branched non-cyclic hydrocarbon having from 1 to 6 carbon atoms. Representative straight chain —(C1-C6)alkyls include -methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl, and -n-hexyl. Representative branched —(C1-C6)alkyls include -iso-propyl, -sec-butyl, -iso-butyl, -tert-butyl, -iso-pentyl, -neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, and 3,3-dimethylbutyl.


“—(C1-C4)alkyl” means a straight chain or branched non-cyclic hydrocarbon having from 1 to 4 carbon atoms. Representative straight chain —(C1-C4)alkyls include -methyl, -ethyl, -n-propyl, and -n-butyl. Representative branched —(C1-C4)alkyls include -iso-propyl, -sec-butyl, -iso-butyl, and -tert-butyl.


“—(C2-C10)alkenyl” means a straight chain or branched non-cyclic hydrocarbon having from 2 to 10 carbon atoms and including at least one carbon-carbon double bond. Representative straight chain and branched (C2-C10)alkenyls include -vinyl, -allyl, -1-butenyl, -2-butenyl, -iso-butylenyl, -1-pentenyl, -2-pentenyl, -3-methyl-1-butenyl, -2-methyl-2-butenyl, -2,3-dimethyl-2-butenyl, -1-hexenyl, -2-hexenyl, -3-hexenyl, -1-heptenyl, -2-heptenyl, -3-heptenyl, -1-octenyl, -2-octenyl, -3-octenyl, -1-nonenyl, -2-nonenyl, -3-nonenyl, -1-decenyl, -2-decenyl, -3-decenyl and the like.


“—(C2-C6)alkenyl” means a straight chain or branched non-cyclic hydrocarbon having from 2 to 6 carbon atoms and including at least one carbon-carbon double bond. Representative straight chain and branched (C2-C6)alkenyls include -vinyl, -allyl, -1-butenyl, -2-butenyl, -iso-butylenyl, -1-pentenyl, -2-pentenyl, -3-methyl-1-butenyl, -2-methyl-2-butenyl, -2,3-dimethyl-2-butenyl, -1-hexenyl, 2-hexenyl, 3-hexenyl and the like.


“—(C2-C10)alkynyl” means a straight chain or branched non-cyclic hydrocarbon having from 2 to 10 carbon atoms and including at least one carbon-carbon triple bond. Representative straight chain and branched —(C2-C10)alkynyls include -acetylenyl, -propynyl, -1-butynyl, -2-butynyl, -1-pentynyl, -2-pentynyl, -3-methyl-1-butynyl, -4-pentynyl, -1-hexynyl, -2-hexynyl, -5-hexynyl, -1-heptynyl, -2-heptynyl, -6-heptynyl, -1-octynyl, -2-octynyl, -7-octynyl, -1-nonynyl, -2-nonynyl, -8-nonynyl, -1-decynyl, -2-decynyl, -9-decynyl and the like.


“—(C2-C6)alkynyl” means a straight chain or branched non-cyclic hydrocarbon having from 2 to 6 carbon atoms and including at least one carbon-carbon triple bond. Representative straight chain and branched (C2-C6)alkynyls include -acetylenyl, -propynyl, -1-butynyl, -2-butynyl, -1-pentynyl, -2-pentynyl, -3-methyl-1-butynyl, -4-pentynyl, -1-hexynyl, -2-hexynyl, -5-hexynyl and the like.


“—(C3-C10)cycloalkyl” means a saturated cyclic hydrocarbon having from 3 to 10 carbon atoms. Representative (C3-C10)cycloalkyls are -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl, -cyclooctyl, -cyclononyl, and -cyclodecyl.


“—(C3-C8)cycloalkyl” means a saturated cyclic hydrocarbon having from 3 to 8 carbon atoms. Representative (C3-C8)cycloalkyls include -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl, and -cyclooctyl.


“—(C8-C14)bicycloalkyl” means a bi-cyclic hydrocarbon ring system having from 8 to 14 carbon atoms and at least one saturated cyclic alkyl ring. Representative —(C8-C14)bicycloalkyls include -indanyl, -1,2,3,4-tetrahydronaphthyl, -5,6,7,8-tetrahydronaphthyl, -perhydronaphthyl and the like.


“—(C8-C14)tricycloalkyl” means a tri-cyclic hydrocarbon ring system having from 8 to 14 carbon atoms and at least one saturated cyclic alkyl ring. Representative —(C8-C14)tricycloalkyls include -pyrenyl, -1,2,3,4-tetrahydroanthracenyl, -perhydroanthracenyl -aceanthreneyl, -1,2,3,4-tetrahydropenanthrenyl, -5,6,7,8-tetrahydrophenanthrenyl, -perhydrophenanthrenyl and the like.


“—(C5-C10)cycloalkenyl” means a cyclic non-aromatic hydrocarbon having at least one carbon-carbon double bond in the cyclic system and from 5 to 10 carbon atoms. Representative (C5-C10)cycloalkenyls include -cyclopentenyl, -cyclopentadienyl, -cyclohexenyl, -cyclohexadienyl, -cycloheptenyl, -cycloheptadienyl, -cycloheptatrienyl, -cyclooctenyl, -cyclooctadienyl, -cyclooctatrienyl, -cyclooctatetraenyl, -cyclononenyl, -cyclononadienyl, -cyclodecenyl, -cyclodecadienyl and the like.


“—(C5-C8)cycloalkenyl” means a cyclic non-aromatic hydrocarbon having at least one carbon-carbon double bond in the cyclic system and from 5 to 8 carbon atoms. Representative (C8-C14)cycloalkenyls include -cyclopentenyl, -cyclopentadienyl, -cyclohexenyl, -cyclohexadienyl, -cycloheptenyl, -cycloheptadienyl, -cycloheptatrienyl, -cyclooctenyl, -cyclooctadienyl, -cyclooctatrienyl, -cyclooctatetraenyl and the like.


“—(C8-C14)bicycloalkenyl” means a bi-cyclic hydrocarbon ring system having at least one carbon-carbon double bond in each ring and from 8 to 14 carbon atoms. Representative —(C8-C14)bicycloalkenyls include -indenyl, -pentalenyl, -naphthalenyl, -azulenyl, -heptalenyl, -1,2,7,8-tetrahydronaphthalenyl and the like.


“—(C8-C14)tricycloalkenyl” means a tri-cyclic hydrocarbon ring system having at least one carbon-carbon double bond in each ring and from 8 to 14 carbon atoms. Representative —(C8-C14)tricycloalkenyls include -anthracenyl, -phenanthrenyl, -phenalenyl, -acenaphthalenyl, as-indacenyl, s-indacenyl and the like.


“-(3- to 7-membered)heterocycle” or “-(3- to 7-membered)heterocyclo” means a 3- to 7-membered monocyclic heterocyclic ring which is either saturated, unsaturated non-aromatic, or aromatic. A 3- or a 4-membered heterocycle can contain up to 3 heteroatoms, a 5-membered heterocycle can contain up to 4 heteroatoms, a 6-membered heterocycle can contain up to 6 heteroatoms, and a 7-membered heterocycle can contain up to 7 heteroatoms. Each heteroatom is independently selected from nitrogen, which can be quaternized; oxygen; and sulfur, including sulfoxide and sulfone. The -(3- to 7-membered)heterocycle can be attached via a nitrogen or carbon atom. Representative -(3- to 7-membered)heterocycles include pyridyl, furyl, thiophenyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, thiadiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrimidinyl, triazinyl, morpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, piperazinyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyrindinyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl and the like.


“-(3- to 5-membered)heterocycle” or “-(3- to 5-membered)heterocyclo” means a 3- to 5-membered monocyclic heterocyclic ring which is either saturated, unsaturated non-aromatic, or aromatic. A 3- or 4-membered heterocycle can contain up to 3 heteroatoms and a 5-membered heterocycle can contain up to 4 heteroatoms. Each heteroatom is independently selected from nitrogen, which can be quaternized; oxygen; and sulfur, including sulfoxide and sulfone. The -(3- to 5-membered)heterocycle can be attached via a nitrogen or carbon atom. Representative -(3- to 5-membered)heterocycles include furyl, thiophenyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, triazinyl, pyrrolidinonyl, pyrrolidinyl, hydantoinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl and the like.


“-(7- to 10-membered)bicycloheterocycle” or “-(7- to 10-membered)bicycloheterocyclo” means a 7- to 10-membered bicyclic, heterocyclic ring which is either saturated, unsaturated non-aromatic, or aromatic. A -(7- to 10-membered)bicycloheterocycle contains from 1 to 4 heteroatoms independently selected from nitrogen, which can be quaternized; oxygen; and sulfur, including sulfoxide and sulfone. The -(7- to 10-membered)bicycloheterocycle can be attached via a nitrogen or carbon atom. Representative -(7- to 10-membered)bicycloheterocycles include -quinolinyl, -isoquinolinyl, -chromonyl, -coumarinyl, -indolyl, -indolizinyl, -benzo[b]furanyl, -benzo[b]thiophenyl, -indazolyl, -purinyl, -4H-quinolizinyl, -isoquinolyl, -quinolyl, -phthalazinyl, -naphthyridinyl, -carbazolyl, -3-carbolinyl and the like.


“—(C14)aryl” means a 14-membered aromatic carbocyclic moiety such as -anthryl or -phenanthryl.


“-(5- to 10-membered)heteroaryl” means an aromatic heterocycle ring of 5 to 10 members, including both mono- and bicyclic ring systems, wherein at least one carbon atom of one or both of the rings is replaced with a heteroatom independently selected from nitrogen, oxygen, and sulfur. In one embodiment one of the -(5- to 10-membered)heteroaryl's rings contain at least one carbon atom. In another embodiment both of the -(5- to 10-membered)heteroaryl's rings contain at least one carbon atom. Representative -(5- to 10-membered)heteroaryls include pyridyl, furyl, benzofuranyl, thiophenyl, benzothiophenyl, quinolinyl, pyrrolyl, indolyl, oxazolyl, benzoxazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrimidinyl, thiadiazolyl, triazinyl, cinnolinyl, phthalazinyl, and quinazolinyl.


“—CH2(halo)” means a methyl group wherein one of the hydrogens of the methyl group has been replaced with a halogen. Representative —CH2(halo) groups include —CH2F, —CH2Cl, —CH2Br, and —CHI2.


“—CH(halo)2” means a methyl group wherein two of the hydrogens of the methyl group have been replaced with a halogen. Representative —CH(halo)2 groups include —CHF2, —CHCl2, —CHBr2, —CHBrCl, —CHClI, and —CHI2.


“—C(halo)3” means a methyl group wherein each of the hydrogens of the methyl group has been replaced with a halogen. Representative —C(halo)3 groups include —CF3, —CCl3, —CBr3, and —Cl3.


“-Halogen” or “-Halo” means —F, —Cl, —Br, or —I.


The phrase “pyridyl group” means




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wherein R1, R2, and n are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “pyrazinyl group” means,




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wherein R1, R2, and p are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “pyrimidinyl group” means




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wherein R1, R2, and p are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “pyridazinyl group” means




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wherein R1, R2, and p are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “thiadiazolyl group” means




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wherein R1 is defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “benzoimidazolyl group” means




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wherein R8 and s are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “benzothiazolyl group” means




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wherein R8 and s are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “benzooxazolyl group” means




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wherein R8 and s are defined above for the Cyclo(hetero)alkenyl Compounds of Formula (I).


The phrase “5-benzodioxolyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-benzodithiolyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-dihydroindenyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-dihydrobenzoimidazolyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “6-dihydrobenzofuranyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-dihydrobenzofuranyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “6-indolinyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-indolinyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “6-dihydrobenzothiopheneyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-dihydrobenzothiopheneyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-dihydrobenzooxazolyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “6-dihydrobenzooxazolyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “5-dihydrobenzothiazolyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “6-dihydrobenzothiazolyl group” means




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where each R9 is independently —H, -halo, or —(C1-C6)alkyl.


The phrase “2-(3-chloropyridyl)” means




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The phrase “2-(3-fluoropyridyl)” means




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The phrase “2-(3-methylpyridyl)” means




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The phrase “2-(3-CF3-pyridyl)” means




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The phrase “2-(3-CHF2-pyridyl)” means




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The phrase “2-(3-hydroxypyridyl)” means




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The phrase “2-(3-nitropyridyl)” means




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The phrase “2-(3-cyanopyridyl)” means




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The phrase “2-(3-bromopyridyl)” means




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The phrase “2-(3-iodopyridyl)” means




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The phrase “4-(5-chloropyrimidinyl)” means




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The phrase “4-(5-methylpyrimidinyl)” means




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The phrase “4-(5-fluoropyrimidinyl)” means




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The phrase “2-(3-chloropyrazinyl)” means




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The phrase “2-(3-methylpyrazinyl)” means




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The phrase “2-(3-fluoropyrazinyl)” means




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The phrase “3-(4-chloropyridazinyl)” means




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The phrase “3-(4-methylpyridazinyl)” means




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The phrase “3-(4-fluoropyridazinyl)” means




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The phrase “5-(4-chlorothiadiazolyl)” means




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The phrase “5-(4-methylthiadiazolyl)” means




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The phrase “5-(4-fluorothiadiazolyl)” means




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The phrase “-(1,1-dimethyl-pentyl)” means




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The phrases “-(1,1-dimethyl-acetic acid) ethyl ester” and “2-methylpropionic acid ethyl ester” mean




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The phrases “-(N-piperidinyl)” and “(piperidin-1-yl)-” mean




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The phrase “cyclo(hetero)alkenyl ring” means




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wherein V, R3 and m are defined above and the numbers designate the position of each atom of the cyclo(hetero)alkenyl ring. The language “(hetero)” means that V is either: N, in which case the cyclo(hetero)alkenyl ring is a tetrahydropyridyl ring; or CH, in which case the cyclo(hetero)alkenyl ring is a cycloalkenyl ring.


The term “animal,” includes, but is not limited to, a cow, monkey, baboon, chimpanzee, horse, sheep, pig, chicken, turkey, quail, cat, dog, mouse, rat, rabbit, guinea pig, and human.


The phrase “pharmaceutically acceptable salt,” as used herein, is any pharmaceutically acceptable salt that can be prepared from a Cyclo(hetero)alkenyl Compound, including a salt formed from an acid and a basic functional group, such as a nitrogen group, of one of the Cyclo(hetero)alkenyl Compounds. Illustrative salts include, but are not limited, to sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucoronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and pamoate (i.e., 1,1′-methylene-bis-(2-hydroxy-3-naphthoate)) salts. The term “pharmaceutically acceptable salt” also includes a salt prepared from a Cyclo(hetero)alkenyl Compound having an acidic functional group, such as a carboxylic acid functional group, and a pharmaceutically acceptable inorganic or organic base. Suitable bases include, but are not limited to, hydroxides of alkali metals such as sodium, potassium, and lithium; hydroxides of alkaline earth metal such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia and organic amines, such as unsubstituted or hydroxy-substituted mono-, di-, or trialkylamines; dicyclohexylamine; tributyl amine; pyridine; N-methyl,N-ethylamine; diethylamine; triethylamine; mono-, bis-, or tris-(2-hydroxy-lower alkyl amines), such as mono-, bis-, or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, or tris-(hydroxymethyl)methylamine, N,N,-di-lower alkyl-N-(hydroxy lower alkyl)-amines, such as N,N,-dimethyl-N-(2-hydroxyethyl)amine, or tri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine, lysine and the like.


The phrase “effective amount,” when used in connection with a Cyclo(hetero)alkenyl Compound means an amount effective for: (a) treating or preventing a Condition; or (b) inhibiting VR1, mGluR1, or mGluR5 function in a cell.


The phrase “effective amount,” when used in connection with another therapeutic agent means an amount for providing the therapeutic effect of the other therapeutic agent.


When a first group is “substituted with one or more” second groups, one or more hydrogen atoms of the first group is replaced with a corresponding number of second groups. When the number of second groups is two or greater, each second group can be the same or different. In one embodiment, the number of second groups is one or two. In another embodiment, the number of second groups is one.


The term “THF” means tetrahydrofuran.


The term “DCM” means dichloromethane.


The term “DCE” means dichloroethane, e.g., 1,1-dichloroethane, 1,2-dichloroethane, or mixtures thereof.


The term “DMF” means dimethylformamide.


The term “DMSO” means dimethyl sulfoxide.


The term “DIEA” means diisopropylethylamine.


The term “TFA” means trifluoroacetic acid.


The term “EtOAc” means ethyl acetate.


The term “Dppp” means 1,3-bis(diphenylphosphino)propane.


The term “Pd(OAc)2” means palladium acetate.


The term “IBD” means inflammatory-bowel disease.


The term “IBS” means irritable-bowel syndrome.


The term “ALS” means amyotrophic lateral sclerosis.


The term “LiHMDS” means lithium hexamethyldisilazide.


The phrases “treatment of,” “treating” and the like include the amelioration or cessation of a Condition or a symptom thereof.


In one embodiment, treating includes inhibiting, for example, decreasing the overall frequency of episodes of a Condition or a symptom thereof.


The phrases “prevention of,” “preventing” and the like include the avoidance of the onset of a Condition or a symptom thereof.


4.3 Methods for Making the Cyclo(Hetero)Alkenyl Compounds

The Cyclo(hetero)alkenyl Compounds can be made using conventional organic synthesis or by the following illustrative methods shown in the schemes below.


4.3.1 Methods for Making the Cyclo(hetero)alkenyl Compounds Where V is N

In one embodiment, the present invention relates to methods for making the Cyclo(hetero)alkenyl Compounds where V is N by the following non-limiting illustrative


method shown below in Scheme A.




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where R1, R2, R3, R4, Ar1, Ar2, m, n and p are defined above and Za is a halogen.


About 1 eq. of a Compound of Formula 1a-h (1M) and 1 eq. of a Compound of Formula 2 are heated in DMSO in the presence of about 1 eq. of DIEA at a temperature of from about 125° C. to about 140° C. for about 12 h. The resulting reaction mixture is cooled to about 25° C. and the solvent removed, e.g., under reduced pressure, to provide an 8-heteroaromatic-1,4-dioxa-8-aza-spiro[4.5]decane Compound of Formula 3a-h. A Compound of Formula 3a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


The Compound of Formula 3a-h can also be obtained by dissolving about 1 equivalent of a Compound of Formula 1a-h (1.5M), a Compound of Formula 2 (about 1.2 eq.), and the sodium salt of 2-methylpropan-2-ol (“NaOtBu”, 1.5 eq.) in glyme and degassing the resulting solution by bubbling nitrogen through the solution. After the solution is degassed, tris-(dibenzylideneacetone)dipalladium (0) catalyst (0.02 eq.) and 0.02 eq. of the ligand depicted below




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is added to the solution and the resulting reaction mixture is heated at a temperature of about 50° C. for about 4.5 h. The reaction mixture is cooled to about 25° C. and solids removed by filtering over CELITE. The solvent is then removed, e.g., under reduced pressure, to provide a residue. The resulting residue can be purified, e.g., using a silica gel column eluted with 6:1 hexane:ethyl acetate.


The Compound of Formula 3a-h can also be obtained by dissolving, e.g., in toluene, about 1 equivalent of a Compound of Formula 1a-h (1.2M), adding to the solution a Compound of Formula 2 (about 1.1 eq.), followed by the addition of NaOtBu (about 1.1 eq.), Pd(OAc)2 (about 0.05 eq.), and 0.05 eq. Dppp (about 0.05 eq.) to form a reaction mixture. The atmosphere in contact with the reaction mixture is replaced by nitrogen. The reaction mixture is stirred and heated to a temperature of from about 25° C. to about the boiling point of the solvent, alternately from about 50° C. to about 100° C., for about 3 h. The reaction mixture is cooled to about 25° C. and worked-up, e.g., as described above, to provide the Compound of Formula 3a-h.


The Compound of Formula 3a-h is then reacted with an acid to provide a Compound of Formula 4a-h. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 3a-h to react with an acid. In another embodiment, the acid is an organic acid, such as TFA, an inorganic acid, such as hydrochloric acid, or their mixtures. For example, the Compound of Formula 3a-h (0.25M) is reacted with 30% TFA in DCM at a temperature of from about 25° C. to about the boiling point of the solvent. Alternatively, the Compound of Formula 3a-h (0.25M) is reacted with about 4N HCl in THF at a temperature of about 50° C. for about 16 hours. Either resulting reaction mixture is cooled to about 25° C. and neutralized with aqueous Na2CO3 such that separate aqueous and organic layers form. The organic layer is separated from the aqueous layer. The aqueous layer is then extracted with DCM and the organic layer and the post-extraction DCM are combined and dried, e.g., with MgSO4 or Na2SO4. The solvent is removed, e.g., under reduced pressure, to provide a 1-heteroaromatic-piperidin-4-one Compound of Formula 4 a-h. The Compound of Formula 4a-h can be purified, e.g., using a silica gel column eluted with 15:1 hexane:ethyl acetate. A Compound of Formula 4a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 4a-h to react with LiHMDS and then an excess triflimide. For example, the Compound of Formula 4a-h (1 eq.) is reacted with 1.25 eq. of LiHMDS at about −78° C. and the resulting reaction mixture allowed to stir at about −78° C. for about 2 h. After stirring for about 2 h, an excess of N-(5-chloro-2-pyridyl)triflimide 5 (1.05 eq. in one embodiment, 3 eq. in another embodiment) is added to the reaction mixture at a temperature of about −78° C. The reaction mixture is stirred for about 2.5 h at a temperature of about −78° C. and then allowed to warm to about 25° C. The solvent is removed, e.g., under reduced pressure, to provide a residue that can be purified, e.g., using a silica gel column eluted with 10:1 hexane:ethyl acetate to provide a Compound of Formula 6a-h. A Compound of Formula 6a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 6a-h to react with a compound of formula Ar2—NHR4. In another embodiment, the reaction in the presence of an organic base, e.g., a trialkylamine. In another embodiment, the reaction in the presence of Pd(OAc)2 and Dppp. In another embodiment, the reaction in the presence of a carbon monoxide atmosphere. For example, about 1 equivalent of the Compound of Formula 6a-h (about LM), an excess of a compound of formula Ar2—NHR4 (about 2 eq.), and a trialkylamine, e.g., triethylamine (from about 1.1 to about 20 eq., about 2.2 eq. in one embodiment), are dissolved in DMF or THF and the resulting solution is degassed by bubbling nitrogen through the solution. Pd(OAc)2 and Dppp (about 0.2-0.3 eq. of each) are added to the solution and the nitrogen atmosphere is replaced with carbon monoxide at a pressure of about 1 atm. The reaction mixture is then heated to about 70° C. for about 2 h. The reaction mixture is cooled to about 25° C. and the solvent removed, e.g., under reduced pressure, to provide a residue. The resulting residue can be purified, e.g., using a silica gel column eluted with 10:1 hexane:ethyl acetate. Where m=1, a mixture of Cyclo(hetero)alkenyl Compounds is generally obtained. The mixture can be separated by conventional methods, for example, column chromatography.


Compounds of formula 2 are commercially available or can be prepared by methods known to those skilled in the art.


The Compound of Formula (I) where X is S (i.e., the Compound of Formula (II′)) can be made by, e.g., reacting a Compound of Formula (II) (i.e., where X is O) with Lawesson's reagent (i.e., 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide) according to the procedures described in Chem. Let. 8:713-4 (1995) or Chem. Let. 12:1398-9 (2000). In one embodiment, the Compound of Formula (I) where X is S can be made by reacting a Compound of Formula (II) (where X is O) with Lawesson's reagent in a nonpolar solvent such as THF or toluene at a temperature of about 100° C. for about 2-3 hours, as shown below:




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In another embodiment, the present invention relates to methods for making the Cyclo(hetero)alkenyl Compounds where V is N from the 8-heteroaromatic-1,4-dioxa-8-aza-spiro[4.5]decane Compounds of Formula 3a-h by the following non-limiting illustrative method shown below in Scheme B.




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where R3, R4, Ar1, Ar2, and m are defined above.


In Step B1 of Scheme B, the Compound of Formula 3a-h, which can be obtained, e.g., as described in Scheme A, is reacted with a ketone-forming reagent, e.g., an inorganic acid such as HCl or H2SO4, or an organic acid, such as trifluoroacetic acid. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 3a-h to react with a ketone-forming reagent. In another embodiment, the ketone-forming reagent is HCl, H2SO4, trifluoroacetic acid or a mixture thereof. In another embodiment, the ketone-forming reagent is HCl. In another embodiment, the ketone-forming reagent is H2SO4. In another embodiment, the ketone-forming reagent is trifluoroacetic acid.


In certain embodiments, the ketone-forming reagent is present in the reaction in Step B1 at an initial concentration within the range of from about IN to about 12N, or at an initial concentration within the range of from about 2N to about 6N. In a specific embodiment, the ketone-forming reagent is present in the reaction at an initial concentration of about 4N.


In certain embodiments, the Compound of Formula 3a-h is present in the reaction in Step B1 at an initial concentration within the range of from about 0.05M to about 10M, or at an initial concentration within the range of from about 0.1M to about 1M. In a specific embodiment, the Compound of Formula 3a-h is present in the reaction at an initial concentration of about 0.25M.


In certain embodiments, the reaction in Step B1 is carried out at a temperature within the range of from about 0° C. to about the boiling point of the solvent; at a temperature within the range of from about 15° C. to about 100° C.; or at a temperature within the range of from about 45° C. to about 55° C.


In certain embodiments, the reaction in Step B1 is carried out in a nonpolar solvent, e.g., hexane, heptane, benzene, diethyl ether, THF, pyridine, DCM, DCE, chloroform, carbon tetrachloride and combinations thereof. In one embodiment, the nonpolar solvent is THF, chloroform or combinations thereof. In another embodiment, the nonpolar solvent is THF. In another embodiment, the nonpolar solvent is chloroform.


In certain embodiments, the Compound of Formula 3a-h is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the ketone-forming reagent. For example, the hydrochloride salt of the Compound of Formula 3a-h is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed, such as by evaporation under reduced pressure, e.g., with a rotary evaporator, to provide the Compound of Formula 3a-h as the free amine.


The reaction in Step B1 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step B1 is carried out in an air atmosphere. In certain embodiments, the reaction in Step B1 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step B1 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step B1 is carried out under an argon atmosphere.


Progress of the reaction in Step B1 can be monitored using conventional analytical techniques, including but not limited to infrared spectroscopy (“IR”), liquid chromatography (“LC”), mass spectrometry (“MS”), liquid chromatography in conjunction with mass spectrometry (“LCMS”), thin-layer chromatography (“TLC”), high-performance liquid chromatography (“HPLC”), gas chromatography (“GC”), gas-liquid chromatography (“GLC”), and/or nuclear magnetic resonance spectroscopy (“NMR”), such as 1H and 13C NMR. The reaction according to Step B1 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a Compound of Formula 4a-h, to starting material, the Compound of Formula 3a-h, remains essentially constant. Typically, a time sufficient for the reaction in Step B1 is within the range of from about 0.5 hours to about 48 hours, from about 1 hour to about 24 hours, or from about 6 hours to about 18 hours. In a specific embodiment, the reaction according to Step B1 is carried out for about 16 hours.


In another embodiment, the reaction according to Step B1 is carried out as described in Scheme A. In another embodiment, the reaction according to Step B1 is carried out in THF with the Compound of Formula 3a-h present at an initial concentration of about 0.35M, with about a 4N initial concentration of HCl, at a temperature of about 50° C., and for a period of about 16 hours with stirring.


The resulting reaction mixture is cooled to about 25° C. and neutralized, e.g., with aqueous Na2CO3, such that separate aqueous and organic layers form. The organic layer is separated from the aqueous layer. The aqueous layer is then extracted, e.g., with ethyl acetate. The organic layer and the post-extraction aliquot(s) are combined and dried, e.g., with MgSO4 or Na2SO4, and the solvent is removed, e.g., under reduced pressure, to provide a 1-heteroaromatic-piperidin-4-one Compound of Formula 4a-h which can be used without further purification or, if desired, can be purified, e.g., using a silica gel column eluted with 3:1 hexane:ethyl acetate.


In Step B2 of Scheme B, the 1-heteroaromatic-piperidin-4-one Compound of Formula 4a-h is reacted with a cyanation reagent, e.g., a cyanide salt such as NaCN, KCN or LiCN. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-heteroaromatic-piperidin-4-one Compound of Formula 4a-h to react with a cyanation reagent. In another embodiment, the cyanide salt is NaCN, KCN, LiCN or a mixture thereof. In another embodiment, the cyanide salt is KCN. In another embodiment, the cyanide salt is NaCN. In another embodiment, the cyanide salt is LiCN. Cyanide salts are commercially available from, e.g., Aldrich Chemical Co., Milwaukee, Wis., or can be prepared by methods known to those skilled in the art.


In certain embodiments, the reaction in Step B2 is carried out with an initial amount of cyanation reagent within the range of from about 1 to about 4 equivalents, or within the range of from about 1.1 to about 2 equivalents, on a molar basis, relative to the Compound of Formula 4a-h. In another embodiment, this reaction is carried out with about 1.2 equivalents, on a molar basis, of cyanation reagent, relative to the Compound of Formula 4a-h.


In certain embodiments, the Compound of Formula 4a-h is present in the reaction in Step B2 at an initial concentration within the range of from about 0.05M to about 10M, or at an initial concentration within the range of from about 0.1M to about 5M. In a specific embodiment, the Compound of Formula 4a-h is present in the reaction at an initial concentration of about 0.3M.


In certain embodiments, the reaction in Step B2 is carried out at a temperature within the range of from about 0° C. to about 100° C.; at a temperature within the range of from about 0° C. to about 60° C.; or at a temperature within the range of from about 0° C. to about 25° C.


In certain embodiments, the reaction in Step B2 is carried out in a polar protic solvent, such as water, an alcohol, e.g., methanol, an organic acid, e.g., acetic acid, an amide, e.g., formamide, or combinations thereof. In one embodiment, the polar protic solvent is water, methanol or combinations thereof. In another embodiment, the polar protic solvent is water. In another embodiment, the polar protic solvent is methanol. In other embodiments, the solvent comprises a mixture of water and a suitable aprotic solvent or solvents, such as acetone, MEK, ethyl acetate, acetonitrile, dioxane, N-methyl-pyrrolidone, DMF, DMAc, DMSO, pyridine, and combinations thereof. In such embodiments the ratio of water to aprotic solvent can be within the range of from about 10:1 to about 1:1 (water:aprotic solvent). In certain embodiments, the aprotic solvent mixed with water is selected from acetone, MEK, ethyl acetate, acetonitrile, dioxane, N-methyl-pyrrolidone, DMF, DMAc, DMSO, pyridine, and combinations thereof.


In certain embodiments, the Compound of Formula 4a-h is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the cyanide salt. For example, the hydrochloride salt of the Compound of Formula 4a-h is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 4a-h as the free amine.


The reaction in Step B2 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step B2 is carried out in an air atmosphere. In certain embodiments, the reaction in Step B2 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step B2 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step B2 is carried out under an argon atmosphere.


Progress of the reaction in Step B2 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step B2 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a Compound of Formula 11a-h, to starting material, the Compound of Formula 4a-h, remains essentially constant. Typically, a time sufficient for the reaction in Step B2 is within the range of from about 0.5 hours to about 36 hours, from about 1 hour to about 24 hours, or from about 4 hours to about 16 hours. In a specific embodiment, the reaction according to Step B2 is carried out for about 12 hours.


In another embodiment, the reaction according to Step B2 is carried out in water with about 1.2 equivalents, on a molar basis, of a cyanide salt, relative to the Compound of Formula 4a-h, at a temperature within the range of from about 0° C. to about 25° C. for a period of about 12 hours with stirring.


Thereafter, the solvent is removed, e.g., under reduced pressure, to provide a residue that can be purified, e.g., using a silica gel column eluted with 3:1 hexane:ethyl acetate, to provide a 1-heteroaromatic-4-hydroxy-piperidine-4-carbonitrile Compound of Formula 11a-h. A Compound of Formula 11a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step B3 of Scheme B, the 1-heteroaromatic-4-hydroxy-piperidine-4-carbonitrile Compound of Formula 11a-h is reacted with a dehydrogenation agent, e.g., POCl3, PSCl3, PCl5, SOCl2 or COCl2. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-heteroaromatic-4-hydroxy-piperidine-4-carbonitrile Compound of Formula 11a-h to react with a dehydrogenation agent. In another embodiment, the dehydrogenation agent is POCl3, PSCl3, PCl5, SOCl2, COCl2 or a mixture thereof. In another embodiment, the dehydrogenation agent is POCl3, PSCl3, SOCl2 or a mixture thereof. In another embodiment, the dehydrogenation agent is POCl3, PSCl3 or a mixture thereof. In another embodiment, the dehydrogenation agent is POCl3. In another embodiment, the dehydrogenation agent is PSCl3. In another embodiment, the dehydrogenation agent is SOCl2. In another embodiment, the dehydrogenation agent is COCl2.


Such dehydrogenation agents are commercially available from, e.g., Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art.


In certain embodiments, the reaction in Step B3 is carried out with an initial amount of dehydrogenation agent within the range of from about 1 to about 10 equivalents, or within the range of from about 1.5 to about 4 equivalents, on a molar basis, relative to the Compound of Formula 11a-h. In another embodiment, this reaction is carried out with about 2.2 equivalents, on a molar basis, of dehydrogenation agent, relative to the Compound of Formula 11a-h.


In certain embodiments, the Compound of Formula 11a-h is present in the reaction in Step B3 at an initial concentration within the range of from about 0.05M to about 10M, or at an initial concentration within the range of from about 0.1M to about 2M. In a specific embodiment, the Compound of Formula 11a-h is present in the reaction at an initial concentration of about 0.25M.


In certain embodiments, the reaction in Step B3 is carried out at a temperature within the range of from about 0° C. to about 100° C.; at a temperature within the range of from about 0° C. to about 60° C.; or at a temperature within the range of from about 15° C. to about 30° C.


In certain embodiments, the reaction in Step B3 is carried out in an aprotic solvent, e.g., acetone, MEK, ethyl acetate, acetonitrile, dioxane, N-methyl-pyrrolidone, DMF, DMAc, DMSO, pyridine, and combinations thereof. In one embodiment, the aprotic solvent is pyridine, dioxane or combinations thereof. In another embodiment, the aprotic solvent is pyridine. In another embodiment, the aprotic solvent is dioxane.


In certain embodiments, the Compound of Formula 11a-h is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the dehydrogenation agent. For example, the hydrochloride salt of the Compound of Formula 11a-h is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 11 a-h as the free amine.


The reaction in Step B3 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step B3 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step B3 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step B3 is carried out under an argon atmosphere.


Progress of the reaction in Step B3 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step B3 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a Compound of Formula 12a-h, to starting material, the Compound of Formula 11a-h, remains essentially constant. Typically, a time sufficient for the reaction in Step B3 is within the range of from about 0.5 hours to about 48 hours, from about 2 hours to about 36 hours, or from about 4 hours to about 24 hours. In a specific embodiment, the reaction according to Step B3 is carried out for about 22 hours.


In another embodiment, the reaction according to Step B3 is carried out in pyridine with about 2.2 equivalents, on a molar basis, of a dehydrogenation agent, relative to the Compound of Formula 11a-h, at a temperature within the range of from about 20° C. to about 25° C. for a period of about 22 hours with stirring.


Thereafter, the solvent is removed, e.g., under reduced pressure, to provide a residue that can be purified, e.g., using a silica gel column eluted with 5:1 hexane:ethyl acetate, to provide a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonitrile Compound of Formula 12a-h. A Compound of Formula 12a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step B4 of Scheme B, the 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonitrile Compound of Formula 12a-h is reacted with an acidifying reagent, e.g., an inorganic acid such as HCl or H2SO4, or an organic acid, such as phthalic acid or tetrahalophthalic acid. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonitrile Compound of Formula 12a-h to react with an acidifying reagent. In another embodiment, the acidifying reagent is HCl, H2SO4, phthalic acid, tetrahalophthalic acid or a mixture thereof. In another embodiment, the acidifying reagent is HCl. In another embodiment, the acidifying reagent is H2SO4. In another embodiment, the acidifying reagent is phthalic acid. In another embodiment, the acidifying reagent is tetrahalophthalic acid.


In certain embodiments, the acidifying reagent is present in the reaction in Step B4 at an initial concentration within the range of from about 0.5N to about 12N, or at an initial concentration within the range of from about IN to about 8N. In a specific embodiment, the acidifying reagent is present in the reaction at an initial concentration of about 6N.


In certain embodiments, the Compound of Formula 12a-h is present in the reaction in Step B4 at an initial concentration within the range of from about 0.05M to about 10M, or at an initial concentration within the range of from about 0.1M to about 5M. In a specific embodiment, the Compound of Formula 12a-h is present in the reaction at an initial concentration of about 0.5M.


In certain embodiments, the reaction in Step B4 is carried out at a temperature within the range of from about 0° C. to about 120° C.; at a temperature within the range of from about 25° C. to about 120° C.; or at a temperature within the range of from about 95° C. to about 105° C.


In certain embodiments, the reaction in Step B4 is carried out in a polar protic solvent or in combinations of such solvents; polar protic solvents have been described above. In one embodiment, the polar protic solvent is water, an organic acid, e.g., formic acid (see U.S. Pat. No. 5,206,392) or combinations thereof. In another embodiment, the polar protic solvent is water. In other embodiments, the solvent comprises a mixture of water and a suitable aprotic solvent or solvents. In such embodiments the ratio of water to aprotic solvent can be within the range of from about 10:1 to about 1:1 (water:aprotic solvent). In certain embodiments, the aprotic solvent mixed with water is selected from acetone, MEK, ethyl acetate, acetonitrile, dioxane, N-methyl-pyrrolidone, DMF, DMAc, DMSO, pyridine, and combinations thereof.


In certain embodiments, the Compound of Formula 12a-h is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the acidifying reagent. For example, the hydrochloride salt of the Compound of Formula 12a-h is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 12 a-h as the free amine.


The reaction in Step B4 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step B4 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step B4 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step B4 is carried out under an argon atmosphere.


Progress of the reaction in Step B4 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step B4 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a Compound of Formula 13a-h, to starting material, the Compound of Formula 12a-h, remains essentially constant. Typically, a time sufficient for the reaction in Step B4 is within the range of from about 0.5 hours to about 36 hours, from about 1 hour to about 24 hours, or from about 4 hours to about 16 hours. In a specific embodiment, the reaction according to Step B4 is carried out for about 12 hours.


In another embodiment, the reaction according to Step B4 is carried out in water with about a 6N initial concentration of HCl, at a temperature within the range of from about 95° C. to about 105° C., and for a period of about 12 hours with refluxing.


The resulting reaction mixture is cooled to about 25° C. and the solvent is removed, e.g., under reduced pressure, to provide a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid Compound of Formula 13a-h, which can be used without further purification or, if desired, can be purified using methods known to those skilled in the art. A Compound of Formula 13a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step B5 of Scheme B, the 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid Compound of Formula 13a-h is reacted in a single step procedure with a compound of formula Ar2—NHR4. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid Compound of Formula 13 a-h to react with a compound of formula Ar2—NHR4. In another embodiment, this reaction is in a single step. In another embodiment, the compound of formula Ar2—NHR4 is 4-trifluoromethyl-aniline. In another embodiment, the compound of formula Ar2—NHR4 is 5-trifluoromethyl-pyridin-2-ylamine. In another embodiment, the compound of formula Ar2—NHR4 is 2,2-difluoro-benzo[1,3]dioxol-5-ylamine. Ar2—NHR4 compounds are commercially available from, e.g., Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art.


In certain embodiments, the reaction in Step B5 is carried out with an initial amount of the a compound of formula Ar2—NHR4 within the range of from about 1 to about 5 equivalents, or within the range of from about 1 to about 2 equivalents, on a molar basis, relative to the Compound of Formula 13a-h. In another embodiment, this reaction is carried out with about 1 equivalent, on a molar basis, of the compound of formula Ar2—NHR4, relative to the Compound of Formula 13a-h.


In certain embodiments, the reaction in Step B5 is carried out to include an initial amount of 1-hydroxybenzotriazole (HOBt) within the range of from about 0.1 to about 3 equivalents, or within the range of from about 0.2 to about 1.5 equivalents, on a molar basis, relative to the Compound of Formula 13a-h. In another embodiment, this reaction is carried out with about 1.25 equivalents, on a molar basis, of HOBt, relative to the Compound of Formula 13a-h.


In certain embodiments, the reaction in Step B5 is carried out to include an initial amount of DIC within the range of from about 0.1 to about 3 equivalents, or within the range of from about 0.2 to about 1.5 equivalents, on a molar basis, relative to the Compound of Formula 13a-h. In another embodiment, this reaction is carried out with about 1.25 equivalents, on a molar basis, of DIC, relative to the Compound of Formula 13 a-h. In another embodiment, this reaction is carried out to include an initial amount of DIC about identical with the initial amount of HOBt, each on a molar basis relative to the Compound of Formula 13a-h. HOBt and DIC are commercially available from, e.g., Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art.


In certain embodiments, the Compound of Formula 13a-h is present in the reaction in Step B5 at an initial concentration within the range of from about 0.05M to about 10M, or at an initial concentration within the range of from about 0.1M to about 1M. In a specific embodiment, the Compound of Formula 13a-h is present in the reaction at an initial concentration of about 0.35M.


In certain embodiments, the reaction in Step B5 is carried out at a temperature within the range of from about 0° C. to about 100° C.; at a temperature within the range of from about 0° C. to about 60° C.; or at a temperature within the range of from about 15° C. to about 30° C.


In certain embodiments, the reaction in Step B5 is carried out in an aprotic solvent or in combinations of such solvents; aprotic solvents have been described above. In one embodiment, the aprotic solvent is pyridine, DMF or combinations thereof. In another embodiment, the aprotic solvent is DMF. In another embodiment, the aprotic solvent is pyridine.


In certain embodiments, the Compound of Formula 13a-h is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the compound of formula Ar2—NHR4. For example, the hydrochloride salt of the Compound of Formula 13a-h is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 13a-h as the free amine.


The reaction in Step B5 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step B5 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step B5 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step B5 is carried out under an argon atmosphere.


Progress of the reaction in Step B5 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step B5 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, the Cyclo(hetero)alkenyl Compound, to starting material, the Compound of Formula 13a-h, remains essentially constant. Typically, a time sufficient for the reaction in Step B5 is within the range of from about 0.5 hours to about 36 hours, from about 1 hour to about 24 hours, or from about 4 hours to about 16 hours. In a specific embodiment, the reaction according to Step B5 is carried out for about 12 hours.


In another embodiment, the reaction according to Step B5 is carried out in DMF with about 1 equivalent of a compound of formula Ar2—NHR4, 1-hydroxybenzotriazole (HOBt, about 1.25 eq.), and DIC (about 1.25 eq.) relative to the Compound of Formula 13a-h (present at an initial concentration of about 0.35M), at a temperature within the range of from about 20° C. to about 25° C. for a period of about 12 hours with stirring.


Thereafter, the solvent is removed, e.g., under reduced pressure, to provide a residue that can be purified, e.g., using a silica gel column eluted with 10:1 hexane:ethyl acetate, to provide a Cyclo(hetero)alkenyl Compound where V is N. Where m=1, a mixture of Cyclo(hetero)alkenyl Compounds where V is N is generally obtained. The mixture can be separated by conventional methods, for example, column chromatography.


A Cyclo(hetero)alkenyl Compound where V is N can also be obtained from a Compound of Formula 13a-h by a two-step procedure, e.g., Step B6 followed by Step B7. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid Compound of Formula 13a-h to react, in a plurality of steps; in one step the reacting is with a compound of formula Ar2—NHR4.


In Step B6 of Scheme B, the 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid Compound of Formula 13a-h is reacted with an excess of a Lewis acid comprising chlorine, such as SOCl2, COCl2, PSCl3, PCl5 or POCl3, which serves as a reagent and can also serve as a solvent. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid Compound of Formula 13 a-h to react with an excess of a Lewis acid comprising chlorine. In another embodiment, the Lewis acid comprising chlorine is POCl3, PSCl3, PCl5, SOCl2, COCl2 or a mixture thereof. In another embodiment, the Lewis acid comprising chlorine is SOCl2, COCl2 or a mixture thereof. In another embodiment, the Lewis acid comprising chlorine is SOCl2. In another embodiment, the Lewis acid comprising chlorine is POCl3. In another embodiment, the Lewis acid comprising chlorine is COCl2.


In certain embodiments, the reaction in Step B6 is carried out with an initial amount of the Lewis acid within the range of from about 1 to about 100 equivalents, or within the range of from about 1 to about 50 equivalents, on a molar basis, relative to the Compound of Formula 13a-h. In another embodiment, this reaction is carried out with about 24 equivalents, on a molar basis, of the Lewis acid, relative to the Compound of Formula 13a-h.


In certain embodiments, the Compound of Formula 13a-h is present in the reaction in Step B6 at an initial concentration within the range of from about 0.05M to about 10M, or at an initial concentration within the range of from about 0.1M to about 5M. In a specific embodiment, the Compound of Formula 13a-h is present in the reaction at an initial concentration of about 0.6M.


In certain embodiments, the reaction in Step B6 is carried out at a temperature within the range of from about 0° C. to about 100° C.; at a temperature within the range of from about 10° C. to about 60° C.; or at a temperature within the range of from about 15° C. to about 30° C.


In certain embodiments, the reaction in Step B6 is carried out in a nonpolar solvent, e.g., THF, an aprotic solvent or in combinations of such solvents; nonpolar solvents and aprotic solvents have been described above. In certain embodiments, the reaction in Step B6 is carried out without a solvent, i.e., the Lewis acid serves as the solvent. In another embodiment, the solvent is THF. In another embodiment, the solvent is SOCl2. In another embodiment, the solvent is POCl3. In another embodiment, the solvent is COCl2.


In certain embodiments, the Compound of Formula 13a-h is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the Lewis acid. For example, the hydrochloride salt of the Compound of Formula 13a-h is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 13a-h as the free amine.


The reaction in Step B6 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step B6 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step B6 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step B6 is carried out under an argon atmosphere.


Progress of the reaction in Step B6 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step B6 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a Compound of Formula 14a-h, to starting material, the Compound of Formula 13a-h, remains essentially constant. Typically, a time sufficient for the reaction in Step B6 is within the range of from about 0.5 hours to about 36 hours, from about 1 hour to about 24 hours, or from about 4 hours to about 19 hours. In a specific embodiment, the reaction according to Step B6 is carried out for about 12 hours. In a specific embodiment, the reaction according to Step B6 is carried out for about 17 hours.


In another embodiment, the reaction according to Step B6 is carried out by reacting the Compound of Formula 13a-h (about 1 eq.) with an excess of a Lewis acid comprising chlorine (about 24 eq.), at a temperature of about 25° C. for a period of about 12 hours with stirring to provide a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonyl chloride Compound of Formula 14a-h, which can be used without further purification or, if desired, can be purified using methods known to those skilled in the art. A Compound of Formula 14a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step B7 of Scheme B, the 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonyl chloride Compound of Formula 14a-h is reacted with a compound of formula Ar2—NHR4. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonyl chloride Compound of Formula 14a-h to react with a compound of formula Ar2—NHR4. In another embodiment, the compound of formula Ar2 NHR4 is 4-trifluoromethyl-aniline. In another embodiment, the compound of formula Ar2—NHR4 is 5-trifluoromethyl-pyridin-2-ylamine. In another embodiment, the compound of formula Ar2—NHR4 is 2,2-difluoro-benzo[1,3]dioxol-5-ylamine.


In certain embodiments, the reaction in Step B7 is carried out with an initial amount of the a compound of formula Ar2—NHR4 within the range of from about 1 to about 10 equivalents, or within the range of from about 1 to about 5 equivalents, on a molar basis, relative to the Compound of Formula 14a-h. In another embodiment, this reaction is carried out with about 1.5 equivalents, on a molar basis, of the compound of formula Ar2—NHR4, relative to the Compound of Formula 14a-h. In another embodiment, this reaction is carried out with about 1.2 equivalents, on a molar basis, of the compound of formula Ar2—NHR4, relative to the Compound of Formula 14a-h. In another embodiment, this reaction is carried out with about 1.1 equivalents, on a molar basis, of the compound of formula Ar2—NHR4, relative to the Compound of Formula 14 a-h.


In certain embodiments, the reaction in Step B7 is carried out to include an initial amount of an organic base, an inorganic base or a mixture thereof. In certain embodiments, the reaction in Step B7 is carried out to include an initial amount of an organic base, e.g., pyridine or a trialkylamine, such as triethylamine, trimethylamine, methyl diethylamine or diisopropyl ethylamine, within the range of from about 1 to about 5 equivalents, or within the range of from about 1 to about 2 equivalents, on a molar basis, relative to the Compound of Formula 14a-h. In another embodiment, this reaction is carried out with about 1.25 equivalents, on a molar basis, of organic base, e.g., trialkylamine, relative to the Compound of Formula 14a-h. In one embodiment, the trialkylamine is triethylamine, trimethylamine, methyl diethylamine, diisopropyl ethylamine or combinations thereof. In another embodiment, the trialkylamine is triethylamine. Trialkylamines are commercially available from, e.g., Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art.


In certain embodiments, the reaction in Step B7 is carried out to include an initial amount of an inorganic base, such as sodium bicarbonate, within the range of from about 1 to about 10 equivalents, or within the range of from about 1 to about 5 equivalents, on a molar basis, relative to the Compound of Formula 14a-h. In another embodiment, this reaction is carried out with about 3 equivalents, on a molar basis, of inorganic base, relative to the Compound of Formula 14a-h. In one embodiment, the inorganic base is sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate or combinations thereof. In another embodiment, the inorganic base is sodium bicarbonate. In another embodiment, the inorganic base is potassium carbonate.


In certain embodiments, the Compound of Formula 14a-h is present in the reaction in Step B7 at an initial concentration within the range of from about 0.05M to about 10M, at an initial concentration within the range of from about 0.1M to about 5M, at an initial concentration within the range of from about 0.1M to about 2M. In a specific embodiment, the Compound of Formula 14a-h is present in the reaction at an initial concentration of about 0.2M. In a specific embodiment, the Compound of Formula 14 a-h is present in the reaction at an initial concentration of about 0.3M. In a specific embodiment, the Compound of Formula 14a-h is present in the reaction at an initial concentration of about 0.5M.


In certain embodiments, the reaction in Step B7 is carried out at a temperature within the range of from about 0° C. to about the boiling point of the solvent; at a temperature within the range of from about 0° C. to about 115° C.; at a temperature within the range of from about 0° C. to about 100° C.; at a temperature within the range of from about 0° C. to about 80° C.; at a temperature within the range of from about 40° C. to about 80° C.; or at a temperature within the range of from about 15° C. to about 30° C.


In certain embodiments, the reaction in Step B7 is carried out in an aprotic solvent or in combinations of such solvents; aprotic solvents have been described above. In one embodiment, the aprotic solvent is DCM, DCE, THF, pyridine or combinations thereof. In another embodiment, the aprotic solvent is DCM. In another embodiment, the aprotic solvent is DCE. In another embodiment, the aprotic solvent is THF. In another embodiment, the aprotic solvent is pyridine. As pyridine can serve in a dual role, i.e., simultaneously serve as a solvent and as an organic base, as discussed above, if such a dual-role organic base is present then the reaction in Step B7 is carried out, in certain embodiments, with an initial amount of the dual-role organic base within the range of from about 1 to about 100 equivalents, or within the range of from about 1 to about 50 equivalents, on a molar basis, relative to the Compound of Formula 14a-h.


In certain embodiments, the Compound of Formula 14a-h is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the compound of formula Ar2—NHR4. For example, the hydrochloride salt of the Compound of Formula 14a-h is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 14a-h as the free amine.


The reaction in Step B7 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step B7 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step B7 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step B7 is carried out under an argon atmosphere.


Progress of the reaction in Step B7 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step B7 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, the Cyclo(hetero)alkenyl Compound, to starting material, the Compound of Formula 14a-h, remains essentially constant. Typically, a time sufficient for the reaction in Step B7 is within the range of from about 0.5 hours to about 24 hours; from about 1 hour to about 19 hours; or from about 1 hour to about 17 hours. In a specific embodiment, the reaction according to Step B7 is carried out for about 1.6 hours. In a specific embodiment, the reaction according to Step B7 is carried out for about 4 hours. In a specific embodiment, the reaction according to Step B7 is carried out for about 16 hours.


In another specific embodiment, the reaction according to Step B7 is carried out in DCM with about 1.5 equivalents of a compound of formula Ar2—NHR4 and a trialkylamine, such as triethylamine, trimethylamine, methyl diethylamine or diisopropyl ethylamine (about 2.0 eq.) relative to the Compound of Formula 14a-h (present at an initial concentration of about 0.2M). The resulting solution is degassed by bubbling nitrogen through the solution. The reaction mixture is kept at a temperature within the range of from about 20° C. to about 25° C. for a period of about 4 hours with stirring.


In another specific embodiment, the reaction according to Step B7 is carried out in pyridine with about 1.2 equivalents of a compound of formula Ar2—NHR4 relative to the Compound of Formula 14a-h (present at an initial concentration of about 0.5M). For example, a 0.5M suspension of the Compound of Formula 14a-h in pyridine can be added to a 0.5M solution of a compound of formula Ar2—NHR4 in pyridine about 25° C. to form a reaction mixture and the reaction mixture is kept at a temperature of about 70° C. for a period of about 16 hours with stirring.


In another specific embodiment, the reaction according to Step B7 is carried out in THF at about 0° C. with about 1.1 equivalents of a compound of formula Ar2—NHR4 and a base, such as sodium bicarbonate (about 3.0 eq.) relative to the Compound of Formula 14 a-h (present at an initial concentration of about 0.3M). The resulting solution is stirred at 0° C. for about 5 min, warmed to about 25° C. over a period of about 30 min with stirring, and kept at about 65° C. for 1 hour with stirring. Thereafter, the solvent is removed, e.g., under reduced pressure, to provide a residue that suspended in ethyl acetate and washed with aqueous 3N HCl such that separate aqueous and organic layers form. The layers can be separated and the aqueous layer extracted with ethyl acetate as required. The organic layer can be combined with the post-extraction ethyl acetate aliquot(s) and the combination dried, e.g., with Na2SO4.


Thereafter, in any of these specific embodiments for conducting the reaction according to Step B7, the solvent is removed, e.g., under reduced pressure, to provide a residue that can be purified, e.g., using a silica gel column eluted with 10:1 hexane:ethyl acetate or using flash chromatography on a silica gel column with 1:1 (by volume) ethyl acetate:hexane as an eluent, to provide a Cyclo(hetero)alkenyl Compound where V is N. As discussed above, if a mixture of Cyclo(hetero)alkenyl Compounds is obtained where m=1, the mixture can be separated by conventional methods, for example, column chromatography.


The Compound of Formula (I) where X is S can be made by, e.g., reacting a Compound of Formula (II) (i.e., where X is O) with Lawesson's reagent as described in connection with Scheme A. In another embodiment, the Compound of Formula (I) where X is S can be made by forming a dithio acid from the Compound of Formula 13a-h, e.g., according to the procedure described in Helvetica Chimica Acta 3:824-33 (1920). The dithio acid can be reacted according to Step B5 of Scheme B or according to the two-step procedure of Scheme B, e.g., Step B6 followed by Step B7, as described above.


Thus, in another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid compound to react with a compound of formula Ar2—NHR4 to provide the Cyclo(hetero)alkenyl Compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises forming the Cyclo(hetero)alkenyl Compound from the 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid compound in one step.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises forming the Cyclo(hetero)alkenyl Compound from the 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid compound in a plurality of steps.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises:


(i) allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid compound to react with a Lewis acid comprising chlorine in a first step to provide a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonyl chloride compound; and


(ii) allowing the 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonyl chloride compound to react with the compound of formula Ar2—NHR4 in a second step to provide a Cyclo(hetero)alkenyl Compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonitrile compound to react with an acidifying reagent to provide a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 1-heteroaromatic-4-hydroxy-piperidine-4-carbonitrile compound to react with a dehydrogenation agent to provide a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carbonitrile compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 1-heteroaromatic-piperidin-4-one compound to react with a cyanation reagent to provide the 1-heteroaromatic-4-hydroxy-piperidine-4-carbonitrile compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 8-heteroaromatic-1,4-dioxa-8-aza-spiro[4.5]decane compound to react with a ketone-forming reagent to provide a 1-heteroaromatic-piperidin-4-one compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 8-heteroaromatic-1,4-dioxa-8-aza-spiro[4.5]decane compound to react with a ketone-forming reagent to provide the 1-heteroaromatic-piperidin-4-one compound.


In another embodiment, the present invention relates to a compound of formula 4 a-h




embedded image



or a pharmaceutically acceptable salt thereof, where:


Ar1 is




embedded image


R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, —C(halo)3, —CH(halo)2, or —CH2(halo);


each R2 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


n is an integer ranging from 0 to 3; and


p is an integer ranging from 0 to 2.


In another embodiment, the present invention relates to a compound of formula 11 a-h




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or a pharmaceutically acceptable salt thereof, where:


Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, —C(halo)3, —CH(halo)2, or —CH2(halo);


each R2 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


n is an integer ranging from 0 to 3; and


p is an integer ranging from 0 to 2.


In another embodiment, the present invention relates to a compound of formula 12 a-h




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or a pharmaceutically acceptable salt thereof, where:


Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, —C(halo)3, —CH(halo)2, or —CH2(halo);


each R2 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteraryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C3-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


n is an integer ranging from 0 to 3; and


p is an integer ranging from 0 to 2.


In another embodiment, the present invention relates to a compound of formula 13 a-h




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or a pharmaceutically acceptable salt thereof, where:


Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, —C(halo)3, —CH(halo)2, or —CH2(halo);


each R2 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, napthyl, —(C14aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


n is an integer ranging from 0 to 3; and


p is an integer ranging from 0 to 2.


In another embodiment, the present invention relates to a compound of formula 14 a-h




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or a pharmaceutically acceptable salt thereof, where:


Ar1 is




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R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, —C(halo)3, —CH(halo)2, or —CH2(halo);


each R2 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


n is an integer ranging from 0 to 3; and


p is an integer ranging from 0 to 2.


In another embodiment, the present invention relates to methods for making the Cyclo(hetero)alkenyl Compounds where V is N from the amino Compounds of Formula 17a-l and the isonicotinoyl chloride Compounds of Formula 16 by the following non-limiting illustrative method shown below in Scheme C.




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where R3, R4, R8, R9, Y, Ar1, Ar2, m, q, r and s are defined above and Z is Cl, Br or I.


In Step C of Scheme C, the isonicotinic acid Compound of Formula 15, which can be obtained, for example, commercially from, e.g., Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art, is reacted with an excess of a Lewis acid comprising chlorine, such as SOCl2, COCl2, PSCl3, PCl5 or POCl3, which serves as a reagent and can also serve as a solvent. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing an isonicotinic acid Compound of Formula 15 to react with an excess of a Lewis acid comprising chlorine. In another embodiment, the Lewis acid comprising chlorine is POCl3, PSCl3, PCl5, SOCl2, COCl2 or a mixture thereof. In another embodiment, the Lewis acid comprising chlorine is SOCl2, COCl2 or a mixture thereof. In another embodiment, the Lewis acid comprising chlorine is SOCl2. In another embodiment, the Lewis acid comprising chlorine is POCl3. In another embodiment, the Lewis acid comprising chlorine is COCl2.


In certain embodiments, the reaction in Step C1 is carried out with an initial amount of the Lewis acid within the range of from about 1 to about 30 equivalents, or within the range of from about 1 to about 20 equivalents, on a molar basis, relative to the Compound of Formula 15. In another embodiment, this reaction is carried out with about 11 equivalents, on a molar basis, of the Lewis acid, relative to the Compound of Formula 15.


In certain embodiments, the Compound of Formula 15 is present in the reaction in Step C1 at an initial concentration within the range of from about LM to about 4M, or at an initial concentration within the range of from about 1M to about 2M. In a specific embodiment, the Compound of Formula 15 is present in the reaction at an initial concentration of about 1.2M.


In certain embodiments, the reaction in Step C1 is carried out at a temperature within the range of from about 10° C. to about 45° C.; at a temperature within the range of from about 10° C. to about 40° C.; or at a temperature within the range of from about 15° C. to about 30° C.


In certain embodiments, the reaction in Step C1 is carried out in an aprotic solvent, e.g., acetone, MEK, ethyl acetate, acetonitrile, dioxane, N-methyl-pyrrolidone, DMF, DMAc, DMSO, pyridine, DCM, DCE and combinations thereof. In certain embodiments, the reaction in Step C1 is carried out without a solvent, i.e., the Lewis acid serves as the solvent. In another embodiment, the solvent is SOCl2.


In certain embodiments, the Compound of Formula 15 is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the Lewis acid. For example, the hydrochloride salt of the Compound of Formula 15 is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 15 as the free amine.


The reaction in Step C1 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step C1 is carried out in an air atmosphere. In certain embodiments, the reaction in Step C1 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step C1 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step C is carried out under an argon atmosphere.


Progress of the reaction in Step C1 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step C1 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a Compound of Formula 16, to starting material, the Compound of Formula 15, remains essentially constant. Typically, a time sufficient for the reaction in Step C1 is within the range of from about 1 hour to about 48 hours, from about 5 hours to about 36 hours, or from about 10 hours to about 24 hours. In a specific embodiment, the reaction according to Step C1 is carried out for about 17 hours.


In another embodiment, the reaction according to Step C1 is carried out by reacting the Compound of Formula 15 (about 1 eq.) with an excess of a Lewis acid comprising chlorine (about 11 eq.), at a temperature of about 25° C. for a period of about 17 hours with stirring to provide an isonicotinolyl chloride Compound of Formula 16, which, after the Lewis acid comprising chlorine is removed, e.g., under reduced pressure, can be used without further purification or, if desired, can be purified. For example, THF can be used to dissolve the Compound of Formula 16 and the solvent can be removed, e.g., under reduced pressure, to provide a purified Compound of Formula 16.


In Step C2 of Scheme C, the isonicotinolyl chloride Compound of Formula 16 is reacted with a compound of formula Ar2—NHR4, e.g., a Compound of Formula 17 a-l. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing an isonicotinolyl chloride Compound of Formula 16 to react with a compound of formula Ar2—NHR4. In another embodiment, the compound of formula Ar2—NHR4 is 4-trifluoromethyl-aniline. In another embodiment, the compound of formula Ar2—NHR4 is 5-trifluoromethyl-pyridin-2-ylamine. In another embodiment, the compound of formula Ar2—NHR4 is 2,2-difluoro-benzo[1,3]dioxol-5-ylamine. In another embodiment, the compound of formula Ar2—NHR4 is 6-fluoro-benzothiazol-2-ylamine.


In certain embodiments, the reaction in Step C2 is carried out with an initial amount of the a compound of formula Ar2—NHR4 within the range of from about 1 to about 2 equivalents, or within the range of from about 1 to about 1.5 equivalents, on a molar basis, relative to the Compound of Formula 16. In another embodiment, this reaction is carried out with about 1.1 equivalents, on a molar basis, of the compound of formula Ar2—NHR4, relative to the Compound of Formula 16.


In certain embodiments, the Compound of Formula 16 is present in the reaction in Step C2 at an initial concentration within the range of from about 0.05M to about 2M, or at an initial concentration within the range of from about 0.1M to about IM. In a specific embodiment, the Compound of Formula 16 is present in the reaction at an initial concentration of about 0.3M.


In certain embodiments, the reaction in Step C2 is carried out to include an initial amount of a base, such as an inorganic base, e.g., sodium bicarbonate, within the range of from about 1 to about 10 equivalents, or within the range of from about 1 to about 5 equivalents, on a molar basis, relative to the Compound of Formula 16. In another embodiment, this reaction is carried out with about 3 equivalents, on a molar basis, of base, relative to the Compound of Formula 16. In one embodiment, the inorganic base is sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate or combinations thereof. In another embodiment, the base is sodium bicarbonate. In another embodiment, the base is potassium carbonate.


In certain embodiments, the reaction in Step C2 is carried out at a temperature within the range of from about −10° C. to about 80° C.; at a temperature within the range of from about −10° C. to about 65° C.; or at a temperature within the range of from about 0° C. to about 65° C.


In certain embodiments, the reaction in Step C2 is carried out in a nonpolar solvent, e.g., hexane, heptane, benzene, diethyl ether, THF, DCM, DCE, chloroform, carbon tetrachloride and combinations thereof. In one embodiment, the nonpolar solvent is THF, DCM, DCE or combinations thereof. In another embodiment, the nonpolar solvent is THF. In another embodiment, the nonpolar solvent is DCM.


In certain embodiments, the Compound of Formula 17 a-l is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction in Step C2. For example, the hydrochloride salt of the Compound of Formula 17 a-l is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed to provide the Compound of Formula 17 a-l as the free amine.


The reaction in Step C2 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step C2 is carried out in an air atmosphere. In certain embodiments, the reaction in Step C2 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step C2 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step C2 is carried out under an argon atmosphere.


Progress of the reaction in Step C2 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step C2 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, the isonicotinamide Compound of Formula 18 a-l, to starting material, the Compound of Formula 16, remains essentially constant. Typically, a time sufficient for the reaction in Step C2 is within the range of from about 5 minutes to about 5 hours, from about 5 minutes to about 3 hours, or from about 15 minutes to about 3 hours. In a specific embodiment, the reaction according to Step C2 is carried out for about 1.6 hours.


In another embodiment, the reaction according to Step C2 is carried out in THF with about 1.1 equivalents of a compound of formula Ar2—NHR4 and a base, such as sodium bicarbonate (about 3 eq.), each relative to the Compound of Formula 16 (present at an initial concentration of about 0.3M). The reaction mixture is kept at a temperature of about 0° C. for about 5 min with stirring, warmed to about 25° C. over about 30 min, then heated to about 65° C. and kept at that temperature for about 1 h to provide an isonicotinamide Compound of Formula 18 a-l, which, after the THF is removed, e.g., under reduced pressure, can be used without further purification or, if desired, can be purified. For example, the Compound of Formula 18 a-l can be suspended in ethyl acetate and washed with aqueous 3N HCl such that separate aqueous and organic layers form. The layers can be separated and the aqueous layer extracted with ethyl acetate as required. The organic layer can be combined with the post-extraction ethyl acetate aliquot(s), the combination dried, e.g., with Na2SO4, and the solvent removed, e.g., under reduced pressure, to provide a purified Compound of Formula 18 a-l. A Compound of Formula 18 a-l is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step C3 of Scheme C, the isonicotinamide Compound of Formula 18 a-l is reacted with an alkylating reagent of the formula Z—CH2—Rz, where Z is Cl, Br or I, and Rz is —H; —(C1-C6)alkyl; —(C3-C8)cycloalkyl or -(3- to 7-membered)heterocyclo, each of which is optionally substituted with one or more R5 groups; or -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is optionally substituted with one or more R6 groups; where R5 and R6 are defined above in connection with the Cyclo(hetero)alkenyl Compounds of Formula (I). In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing an isonicotinamide Compound of Formula 18 a-l to react with an alkylating reagent of the formula Z—CH2—Rz. In another embodiment, Rz is —H; —(C1-C6)alkyl; or -phenyl, which is optionally substituted with one or more R6 groups. In another embodiment, Rz is —H, —(C1-C4)alkyl, or -phenyl which is unsubstituted. In another embodiment, Rz is -phenyl which is unsubstituted. Exemplary alkylating reagents include methyl iodide, methyl bromide, ethyl iodide, ethyl bromide, benzyl bromide, benzyl iodide, benzyl chloride, 4-methoxybenzyl bromide, and 4-methoxybenzyl iodide. In another embodiment, the alkylating reagent is a benzylating reagent, i.e., comprises a benzyl group. Exemplary benzylating reagents include benzyl bromide, benzyl iodide, benzyl chloride, 4-methoxybenzyl bromide, 4-methoxybenzyl iodide, 4-methoxybenzyl chloride, or a mixture thereof. In another embodiment, the benzylating reagent is benzyl bromide, benzyl iodide, benzyl chloride or a mixture thereof. In another embodiment, the benzylating reagent is benzyl bromide. In another embodiment, the benzylating reagent is benzyl iodide. In another embodiment, the benzylating reagent is benzyl chloride. In another embodiment, sodium iodide, potassium iodide, tetrabutylammonium iodide, or combinations thereof is present with an alkylating reagent comprising chlorine.


In certain embodiments, the alkylating reagent is present in the reaction in Step C3 at an initial concentration within the range of from about 0.05M to about 2M, or at an initial concentration within the range of from about 0.1M to about 2M. In a specific embodiment, the Compound of Formula 18 a-l is present in the reaction at an initial concentration of about 0.35M.


In certain embodiments, the Compound of Formula 18 a-l is present in the reaction in Step C3 at an initial concentration within the range of from about 0.05M to about 5M, or at an initial concentration within the range of from about 0.1M to about 2M. In a specific embodiment, the Compound of Formula 18 a-l is present in the reaction at an initial concentration of about 0.24M.


In certain embodiments, the reaction in Step C3 is carried out at a temperature within the range of from about 60° C. to about the boiling point of the solvent; at a temperature within the range of from about 65° C. to about 100° C.; or at a temperature within the range of from about 75° C. to about 85° C.


In certain embodiments, the reaction in Step C3 is carried out in a nonpolar solvent, e.g., hexane, heptane, benzene, diethyl ether, THF, DCM, DCE, chloroform, carbon tetrachloride and combinations thereof. In one embodiment, the nonpolar solvent is THF, DMF or combinations thereof. In another embodiment, the nonpolar solvent is a mixture of THF and DMF. In another embodiment, the mixture of THF:DMF is from about 8:1 to about 1:1, or from about 5:1 to about 1:1 by volume. In another embodiment, the mixture of THF:DMF is about 4:1 by volume.


In certain embodiments, the Compound of Formula 18 a-l is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art prior to reaction with the alkylating reagent. For example, the hydrochloride salt of the Compound of Formula 18 a-l is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed, such as by evaporation under reduced pressure, e.g., with a rotary evaporator, to provide the Compound of Formula 18 a-l as the free amine.


The reaction in Step C3 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step C3 is carried out in an air atmosphere. In certain embodiments, the reaction in Step C3 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step C3 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step C3 is carried out under an argon atmosphere.


Progress of the reaction in Step C3 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step C3 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a 1-alkylated-isonicotinamide Compound of Formula 19 a-l, to starting material, the Compound of Formula 18 a-l, remains essentially constant. Typically, a time sufficient for the reaction in Step C3 is within the range of from about 1 hour to about 48 hours, from about 3 hours to about 48 hours, or from about 10 hours to about 36 hours. In a specific embodiment, the reaction according to Step C3 is carried out for about 24 hours.


In another embodiment, the reaction according to Step C3 is carried out in 4:1 THF:DMF by volume with the Compound of Formula 18 a-l present at an initial concentration of about 0.24M, with about a 0.35M initial concentration of benzyl bromide, at a temperature of about 80° C., and for a period of about 24 hours under reflux. Thereafter, the 1-alkylated-isonicotinamide Compound of Formula 19 a-l is recovered using methods known to those skilled in the art. For example, the reaction mixture can be cooled to about 25° C. and the resulting solid can be filtered off. A majority of the THF can be removed from the filtrate, e.g., under reduced pressure. Diethyl ether can be added to cause a precipitate to form from the DMF-enriched solution. The resulting solid can be filtered off and the solids can be combined and dried to provide the 1-alkylated-isonicotinamide Compound of Formula 19 a-l. A Compound of Formula 19 a-l is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step C4 of Scheme C, the 1-alkylated-isonicotinamide Compound of Formula 19 a-l is reacted with a hydrogenation agent, e.g., NaBH4 or LiBH4. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-alkylated-isonicotinamide Compound of Formula 19 a-l to react with a hydrogenation agent. In another embodiment, the hydrogenation agent is NaBH4, LiBH4 or a mixture thereof. In another embodiment, the hydrogenation agent is NaBH4. Hydrogenation agents are commercially available from, e.g., Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art.


In certain embodiments, the reaction in Step C4 is carried out with an initial amount of hydrogenation agent within the range of from about 1 to about 10 equivalents, or within the range of from about 1 to about 6 equivalents, on a molar basis, relative to the Compound of Formula 19 a-l. In another embodiment, this reaction is carried out with about 3.2 equivalents, on a molar basis, of hydrogenation agent, relative to the Compound of Formula 19 a-l.


In certain embodiments, the Compound of Formula 19 a-l is present in the reaction in Step C4 at an initial concentration within the range of from about 0.01M to about 5M, or at an initial concentration within the range of from about 0.05M to about 2M. In a specific embodiment, the Compound of Formula 19 a-l is present in the reaction at an initial concentration of about 0.18M.


In certain embodiments, the reaction in Step C4 is carried out at a temperature within the range of from about −10° C. to about 50° C.; at a temperature within the range of from about −10° C. to about 40° C.; or at a temperature within the range of from about 0° C. to about 30° C.


In certain embodiments, the reaction in Step C4 is carried out in a polar protic nonaqueous solvent, such as an alcohol, e.g., methanol, ethanol, a dialkylamide, e.g., dimethyl formamide, dimethyl formamide, methyl ethyl formamide, or combinations thereof. In one embodiment, the polar protic nonaqueous solvent is an alcohol, a dialkylamide or combinations thereof. In another embodiment, the polar protic nonaqueous solvent is methanol, ethanol, isopropanol or combinations thereof. In another embodiment, the polar protic nonaqueous solvent is methanol. In another embodiment, the polar protic nonaqueous solvent is dimethyl formamide, dimethyl formamide, methyl ethyl formamide or combinations thereof. In another embodiment, the polar protic nonaqueous solvent is dimethyl formamide.


The reaction in Step C4 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step C4 is carried out in an air atmosphere. In certain embodiments, the reaction in Step C4 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step C4 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step C4 is carried out under an argon atmosphere.


Progress of the reaction in Step C4 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step C4 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a 1-alkylated-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 20 a-l, to starting material, the Compound of Formula 19 a-l, remains essentially constant. Typically, a time sufficient for the reaction in Step C4 is within the range of from about 5 minutes to about 10 hours, from about 5 minutes to about 5 hours, or from about 15 minutes to about 5 hours. In a specific embodiment, the reaction according to Step C4 is carried out for about 3.5 hours.


In another embodiment, the reaction according to Step C4 is carried out at about 0° C. in an alcohol with about 3.2 equivalents, on a molar basis, of a hydrogenation agent, relative to the Compound of Formula 19 a-l, added portion-wise over a period of about 30 min. Thereafter, the reaction mixture can be stirred for about 1 h at about 0° C. and warmed to about 25° C. over about a 2 hour period to provide a 1-alkylated-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 20 a-l, which, after the alcohol is removed, e.g., under reduced pressure, can be used without further purification or, if desired, can be purified. For example, the Compound of Formula 20 a-l can be diluted with brine and ethyl acetate such that separate aqueous and organic layers form. The layers can be separated and the aqueous layer washed with ethyl acetate as required. The organic layer can be combined with the post-washing ethyl acetate aliquot(s), the combination dried, e.g., with Na2SO4, and the solvent removed, e.g., under reduced pressure, to provide purified Compound of Formula 20 a-l which can be used without additional purification or, if desired, can be further purified. For example, the purified Compound of Formula 20 a-l can be dissolved in DCM and precipitated by adding hexane to the DCM solution. The resulting solid can be filtered off and dried to provide further purified Compound of Formula 20 a-l. A Compound of Formula 20 a-l is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step C5 of Scheme C, the 1-alkylated-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 20 a-l is reacted with a dealkylating reagent, e.g., α-chloroethylchloroformate. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1-alkylated-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 20 a-l to react with a dealkylating reagent. In another embodiment, the dealkylating reagent is α-chloroethylchloroformate, 2,2,2-trichloroethylchloroformate or a mixture thereof. In another embodiment, the dealkylating reagent is α-chloroethylchloroformate. In another embodiment, the dealkylating reagent is 2,2,2-trichloroethylchloroformate. Dealkylating reagents are commercially available from, e.g., Aldrich Chemical Co., or can be prepared by methods known to those skilled in the art.


In certain embodiments, the dealkylating reagent is present in the reaction in Step C5 at an initial concentration within the range of from about 0.05M to about 4M, or at an initial concentration within the range of from about 0.06M to about 4M. In a specific embodiment, the dealkylating reagent is present in the reaction at an initial concentration of about 0.32M.


In certain embodiments, the Compound of Formula 20 a-l is present in the reaction in Step C5 at an initial concentration within the range of from about 0.01M to about 5M, or at an initial concentration within the range of from about 0.05M to about 2M. In a specific embodiment, the Compound of Formula 20 a-l is present in the reaction at an initial concentration of about 0.17M.


In certain embodiments, the reaction in Step C5 is carried out at a temperature within the range of from about 0° C. to about the boiling point of the solvent; at a temperature within the range of from about 0° C. to about 100° C.; or at a temperature within the range of from about 0° C. to about 90° C.


In certain embodiments, the reaction in Step C5 is carried out in a nonpolar solvent, e.g., hexane, heptane, benzene, diethyl ether, THF, DCM, DCE, chloroform, carbon tetrachloride and combinations thereof. In one embodiment, the nonpolar solvent is DCE, THF or combinations thereof. In another embodiment, the nonpolar solvent is DCE. In another embodiment, the nonpolar solvent is THF.


In certain embodiments, the Compound of Formula 20 a-l is provided as a salt, e.g., the hydrochloride salt, which can be converted to the free amine, using procedures known in the art, prior to reaction with the dealkylating reagent. For example, the hydrochloride salt of the Compound of Formula 20 a-l is dissolved in a suitable organic solvent, such as but not limited to chloroform, to provide a solution that is extracted with, e.g., a saturated aqueous solution of Na2CO3. The organic layer is recovered and the aqueous layer back-extracted with an additional volume of the organic solvent. The organic solvent layers are combined, extracted with water, dried, e.g., over anhydrous sodium sulfate, and then the liquid is removed, such as by evaporation under reduced pressure, e.g., with a rotary evaporator, to provide the Compound of Formula 20 a-l as the free amine.


The reaction in Step C5 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step C5 is carried out in an air atmosphere. In certain embodiments, the reaction in Step C5 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step C5 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step C5 is carried out under an argon atmosphere.


Progress of the reaction in Step C5 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step C5 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, a 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 21 a-l, to starting material, the Compound of Formula 20 a-l, remains essentially constant. Typically, a time sufficient for the reaction in Step C5 is within the range of from about 0.3 hours to about 48 hours, from about 0.5 hours to about 48 hours, or from about 0.5 hours to about 5 hours. In a specific embodiment, the reaction according to Step C5 is carried out for about 4.75 hours.


In another embodiment, the reaction according to Step C5 is carried out in DCE with the Compound of Formula 20 a-l present at an initial concentration of about 0.17M, with about a 0.32M initial concentration of α-chloroethylchloroformate (after adding drop-wise over a 15 minute period) at a temperature of about 0° C. The reaction mixture can be warmed to about 25° C. over a period of about 30 min then heated to about 83° C. for about 4 hours at that temperature to provide a 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 21 a-l, which, after the solvent and unreacted α-chloroethylchloroformate are removed, e.g., under reduced pressure, can be used without further purification or, if desired, can be purified. For example, the Compound of Formula 21 a-l can be dissolved in methanol, refluxed for about 3 hours at a temperature of about 65° C., and the methanol removed, e.g., under reduced pressure, to provide purified Compound of Formula 21 a-l which can be used without additional purification or, if desired, can be further purified. For example, the purified Compound of Formula 21 a-l can be dissolved in DCM and precipitated by adding diethyl ether to the DCM solution. The resulting solid can be filtered off and dried to provide further purified Compound of Formula 21 a-l. A Compound of Formula 21 a-l is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


In Step C6 of Scheme C, the 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 21 a-l is reacted with a compound of formula Ar1—Z, where Z is Cl, Br or I. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide Compound of Formula 21 a-l to react with a compound of formula Ar1—Z. In another embodiment, the compound of formula Ar1—Z is 2-chloro-3-nitropyridine. In another embodiment, the compound of formula Ar1—Z is 2,3-dichloropyridine. In another embodiment, the compound of formula Ar1—Z is 2-chloro-3-fluoropyridine.


In certain embodiments, the compound of formula Ar1—Z is present in the reaction in Step C6 at an initial concentration within the range of from about 0.01M to about 5M, or at an initial concentration within the range of from about 0.05M to about 3M. In a specific embodiment, the compound of formula Ar—Z is present in the reaction at an initial concentration of about 0.064M.


In certain embodiments, the Compound of Formula 21 a-l is present in the reaction in Step C6 at an initial concentration within the range of from about 0.01M to about 5M, or at an initial concentration within the range of from about 0.05M to about 3M. In a specific embodiment, the Compound of Formula 21 a-l is present in the reaction at an initial concentration of about 0.068M.


In certain embodiments, a trialkylamine, such as triethylamine, trimethylamine, methyl diethylamine or diisopropyl ethylamine, is present in the reaction in Step C6 at an initial concentration within the range of from about 0.01M to about 5M, or at an initial concentration within the range of from about 0.05M to about 3M. In a specific embodiment, the trialkylamine is present in the reaction at an initial concentration of about 0.27M. In one embodiment, the trialkylamine is triethylamine, trimethylamine, methyl diethylamine, diisopropyl ethylamine or combinations thereof. In another embodiment, the trialkylamine is triethylamine.


In certain embodiments, the reaction in Step C6 is carried out at a temperature within the range of from about 15° C. to about 140° C.; at a temperature within the range of from about 25° C. to about 140° C.; or at a temperature within the range of from about 15° C. to about 30° C.


In certain embodiments, the reaction in Step C6 is carried out in a solvent, e.g., hexane, heptane, benzene, diethyl ether, THF, DCM, DCE, chloroform, carbon tetrachloride, DMF, DMSO, and combinations thereof. In one embodiment, the nonpolar solvent is DCE, THF or combinations thereof. In another embodiment, the nonpolar solvent is DCE.


The reaction in Step C6 can be carried out at reduced pressure, atmospheric pressure or elevated pressure, i.e., greater than atmospheric pressure. In one embodiment, the reaction is carried out at atmospheric pressure. In certain embodiments, the reaction in Step C6 is carried out in an air atmosphere. In certain embodiments, the reaction in Step C6 is carried out in an inert atmosphere. In one non-limiting aspect of this embodiment, the reaction in Step C6 is carried out under a nitrogen atmosphere. In another non-limiting aspect of this embodiment, the reaction in Step C6 is carried out under an argon atmosphere.


Progress of the reaction in Step C6 can be monitored using conventional analytical techniques, including but not limited to IR, LC, MS, LCMS, TLC, HPLC, GC, GLC and/or NMR. The reaction according to Step C6 is carried out, in one embodiment, until a starting material is consumed or, in another embodiment, until the ratio of product, the Cyclo(hetero)alkenyl Compound, to starting material, the Compound of Formula 21 a-l, remains essentially constant. Typically, a time sufficient for the reaction in Step C6 is within the range of from about 0.5 hours to about 48 hours, from about 0.5 hours to about 36 hours, or from about 3 hours to about 24 hours. In a specific embodiment, the reaction according to Step C6 is carried out for about 12 hours.


In another embodiment, the reaction according to Step C6 is carried out in DCE with about 0.064M of a compound of formula Ar1—Z, about 0.068M of a Compound of Formula 21 a-l, and about 0.27M of a trialkylamine, such as triethylamine, trimethylamine, methyl diethylamine or diisopropyl ethylamine. The reaction mixture is kept at a temperature within the range of from about 20° C. to about 30° C. for a period of about 12 hours with stirring. Thereafter, the mixture can be poured into aqueous sodium bicarbonate and DCM such that separate aqueous and organic layers form. The organic layer is separated from the aqueous layer. The organic layer is dried, e.g., with Na2SO4, and the solvent is removed, e.g., under reduced pressure, to provide a residue that can be used without further purification or, if desired, can be purified to provide a Cyclo(hetero)alkenyl Compound where V is N. For example, the residue can be dissolved in DCM and precipitated by adding hexane to the DCM solution. The resulting solid can be filtered off and dried to provide a purified Cyclo(hetero)alkenyl Compound where V is N. As discussed above, if a mixture of Cyclo(hetero)alkenyl Compounds is obtained where m=1, the mixture can be separated by conventional methods, for example, column chromatography.


The Compound of Formula (I) where X is S (i.e., the Compound of Formula (II′)) can be made by, e.g., reacting a Compound of Formula (II) (i.e., where X is O) with Lawesson's reagent as described in connection with Scheme A.


Thus, in another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide compound to react with a compound of formula Ar1—Z to provide a Cyclo(hetero)alkenyl Compound; where Z is Cl, Br or I.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 1-alkylated-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide compound to react with a dealkylating reagent to provide a 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing a 1-alkylated-isonicotinamide compound to react with a hydrogenation agent to provide a 1-alkylated-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide compound.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises allowing an isonicotinamide compound to react with an alkylating reagent to provide a 1-alkylated-isonicotinamide compound.


In another embodiment, in method for preparing a Cyclo(hetero)alkenyl Compound, the alkylating reagent is a benzylating reagent selected from benzyl bromide, benzyl iodide, benzyl chloride or a mixture thereof.


In another embodiment, a method for preparing a Cyclo(hetero)alkenyl Compound comprises forming the isonicotinamide compound by allowing an isonicotinolyl chloride compound to react with a compound of formula Ar2—NHR4;


where R4 is —H or —(C1-C6)alkyl; and


Ar2 is




embedded image


where Y1 and Y2 are —CH2— and —CH2—, —O— and —O—, —NH— and —NH—, —S— and —S—, —CH2— and —O—, —CH2— and —NH—, —CH2— and —S—, —O— and —CH2—, —NH— and —CH2—, —S— and —CH2—, —O— and —NH—, —NH— and —O—, —S— and —NH—, or —NH— and —S— respectively;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each R8 is independently —(C1-C10)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —R7OR7, —R7COR7, —R7C(O)OR7, —R7OC(O)R7, —R7OC(O)OR7, —R7SR7, —R7S(O)R7, —R7S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), —C(OH)(CF3)2, —(C1-C10)alkyl, or -(3- to 7-membered)heterocycle;


each R9 is independently —H, -halo or —(C1-C6)alkyl,


each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7;


each halo is independently —F, —Cl, —Br, or —I;


q is an integer ranging from 0 to 6;


r is an integer ranging from 0 to 5; and


s is an integer ranging from 0 to 4.


In another embodiment, the present invention relates to a compound of formula 18 a-l




embedded image



or a pharmaceutically acceptable salt thereof, where:


Ar2 is




embedded image


Y1 and Y2 are —CH2— and —CH2—, —O— and —O—, —NH— and —NH—, —S— and —S—, —CH2— and —O—, —CH2— and —NH—, —CH2— and —S—, —O— and —CH2—, —NH— and —CH2—, —S— and —CH2—, —O— and —NH—, —NH— and —O—, —S— and —NH—, or —NH— and —S— respectively;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, -(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


R4 is —H or —(C1-C6)alkyl;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each R8 is independently —(C1-C10)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —R7OR7, —R7COR7, —R7C(O)OR7, —R7OC(O)R7, —R7OC(O)OR7, —R7SR7, —R7S(O)R7, —R7S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), —C(OH)(CF3)2, —(C1-C10)alkyl, or -(3- to 7-membered)heterocycle;


each R9 is independently —H, -halo or —(C1-C6)alkyl;


each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7;


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


q is an integer ranging from 0 to 6;


r is an integer ranging from 0 to 5; and


s is an integer ranging from 0 to 4.


In another embodiment, the present invention relates to a compound of formula 19 a-l




embedded image



or a pharmaceutically acceptable salt thereof, where:


Ar2 is




embedded image


Y1 and Y2 are —CH2— and —CH2—, —O— and —O—, —NH— and —NH—, —S— and —S—, —CH2— and —O—, —CH2— and —NH—, —CH2— and —S—, —O— and —CH2—, —NH— and —CH2—, —S— and —CH2—, —O— and —NH—, —NH— and —O—, —S— and —NH—, or —NH— and —S— respectively each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


R4 is —H or —(C1-C6)alkyl;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each R8 is independently —(C1-C10)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —R7OR7, —R7COR7, —R7C(O)OR7, —R7OC(O)R7, —R7OC(O)OR7, —R7SR7, —R7S(O)R7, —R7S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), —C(OH)(CF3)2, —(C1-C10)alkyl, or -(3- to 7-membered)heterocycle;


each R9 is independently —H, -halo or —(C1-C6)alkyl;


each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7;


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


q is an integer ranging from 0 to 6;


r is an integer ranging from 0 to 5;


s is an integer ranging from 0 to 4;


Rz is -phenyl which is optionally substituted with one or more R6 groups, —H or —(C1-C6)alkyl; and


Z is Cl, Br or I.


In another embodiment, the present invention relates to a compound of formula 20 a-l




embedded image



or a pharmaceutically acceptable salt thereof, where:


Ar2 is




embedded image


Y1 and Y2 are —CH2— and —CH2—, —O— and —O—, —NH— and —NH—, —S— and —S—, —CH2— and —O—, —CH2— and —NH—, —CH2— and —S—, —O— and —CH2—, —NH— and —CH2—, —S— and —CH2—, —O— and —NH—, —NH— and —O—, —S— and —NH—, or —NH— and —S— respectively;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


R4 is —H or —(C1-C6)alkyl;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each R8 is independently —(C1-C10)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —R7OR7, —R7COR7, —R7C(O)OR7, —R7OC(O)R7, —R7OC(O)OR7, —R7SR7, —R7S(O)R7, —R7S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), —C(OH)(CF3)2, —(C1-C10)alkyl, or -(3- to 7-membered)heterocycle;


each R9 is independently —H, -halo or —(C1-C6)alkyl;


each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7;


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


q is an integer ranging from 0 to 6;


r is an integer ranging from 0 to 5;


s is an integer ranging from 0 to 4; and


Rz is -phenyl which is optionally substituted with one or more R6 groups, —H or —(C1-C6)alkyl.


In another embodiment, the present invention relates to a compound of formula 21 a-l




embedded image



or a pharmaceutically acceptable salt thereof, where:


Ar2 is




embedded image


Y1 and Y2 are —CH2— and —CH2—, —O— and —O—, —NH— and —NH—, —S— and —S—, —CH2— and —O—, —CH2— and —NH—, —CH2— and —S—, —O— and —CH2—, —NH— and —CH2—, —S— and —CH2—, —O— and —NH—, —NH— and —O—, —S— and —NH—, or —NH— and —S— respectively;


each R3 is independently:

    • (a) -halo, —CN, —OH, —NO2, or —NH2,
    • (b) —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups, or
    • (c) -phenyl, -naphthyl, —(C14)aryl or -(5- to 10-membered) heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;


R4 is —H or —(C1-C6)alkyl;


each R5 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7;


each R7 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, -(3- to 5-membered)heterocycle, —C(halo)3, —CH(halo)2, or CH2(halo);


each R8 is independently —(C1-C10)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, —S(O)2R7, —R7OR7, —R7COR7, —R7C(O)OR7, —R7OC(O)R7, —R7OC(O)OR7, —R7SR7, —R7S(O)R7, —R7S(O)2R7, —C(halo)2C(halo)3, —C(halo)2CH(halo)2, —CH(C(halo)3)2, —CH(C(halo)3)(CH3), —OC(halo)2C(halo)3, —OC(halo)2CH(halo)2, —OCH(C(halo)3)2, —OCH(C(halo)3)(CH3), —C(OH)(CF3)2, —(C1-C10)alkyl, or -(3- to 7-membered)heterocycle;


each R9 is independently —H, -halo or —(C1-C6)alkyl;


each R11 is independently —CN, —OH, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, or —OC(O)OR7;


each halo is independently —F, —Cl, —Br, or —I;


m is 0 or 1 and when m is 1, R3 is attached to the 2-, 3-, 5-, or 6-position of the cyclo(hetero)alkenyl ring;


q is an integer ranging from 0 to 6;


r is an integer ranging from 0 to 5; and


s is an integer ranging from 0 to 4.


4.3.2 Methods for Making the Cyclo(hetero)alkenyl Compounds Where V is CH

In another embodiment, the present invention relates to methods for making the Cyclo(hetero)alkenyl Compounds where V is CH by the following non-limiting illustrative method shown below in Scheme D.




embedded image


embedded image



where R1, R2, R3, R4, Ar1, Ar2, m, n and p are defined above.


A Compound of Formula 1a-h is reacted with butyl lithium in diethyl ether/THF and then with a Compound of Formula 7 according to the procedure described in J. Med. Chem. 32(2):351-7 (1989) to provide a Compound of Formula 8a-h. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 1a-h to react with butyl lithium and then with a Compound of Formula 7. A Compound of Formula 8a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


The Compound of Formula 8a-h is then reacted with a Lewis acid, e.g., SOCl2/pyridine, hydrogenated using a Pd catalyst in ethyl acetate, and reacted with trifluoroacetic acid in water according to the procedure described in J. Med. Chem. 32(2):351-7 (1989) to provide a Compound of Formula 9a-h. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 8a-h to react with a Lewis acid, then hydrogenating the product, and allowing the hydrogenated product to react with trifluoroacetic acid. A Compound of Formula 9a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


The Compound of Formula 9a-h is then reacted with (CF3SO2)2O in the presence of methyl-di-(tert-butyl)-pyridine in DCM according to the procedure described in J. Org. Chem. 54(12):2886-9 (1989) or Organic Syntheses 68:116-29 (1980) to provide a


Compound of Formula 10a-h. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 9a-h to react with (CF3SO2)2O. In another embodiment, this reaction is in the presence of methyl-di-(tert-butyl)-pyridine. A Compound of Formula 10a-h is useful, e.g., as an intermediate for the synthesis of a Cyclo(hetero)alkenyl Compound.


The Compound of Formula 10a-h is then reacted with an amine of formula Ar2—NHR4 in the presence of palladium pentadione, triphenylphosphine, and lithium chloride in THF under an atmosphere of carbon monoxide according to the procedure described in Tetrahedron Letters 33(9): 1181-4 (1992) to provide the Cyclo(hetero)alkenyl Compound where V is CH. In one embodiment, the present invention relates to a method for making a Cyclo(hetero)alkenyl Compound comprising allowing a Compound of Formula 10a-h to react with an amine of formula Ar2—NHR4. In another embodiment, this reaction is in the presence of palladium pentadione, triphenylphosphine, and lithium chloride. In another embodiment, this reaction is under an atmosphere of carbon monoxide.


Compounds of formula 7 are commercially available or can be prepared by methods known to those skilled in the art.


Where m=1, a mixture of Cyclo(hetero)alkenyl Compounds is generally obtained. The mixture can be separated by conventional methods, for example, column chromatography.


The Compound of Formula (I) where X is S (i.e., the Compound of Formula (III′)) can be made by, e.g., reacting a Compound of Formula (III) (i.e., where X is O) with Lawesson's reagent as described in connection with Scheme A. This reaction is illustrated below:




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Certain Cyclo(hetero)alkenyl Compounds can have asymmetric centers and therefore exist in different enantiomeric and diastereomeric forms. A Cyclo(hetero)alkenyl Compound can be in the form of an optical isomer or a diastereomer. Accordingly, the invention encompasses Cyclo(hetero)alkenyl Compounds and their uses as described herein in the form of their optical isomers, diasteriomers and mixtures thereof, including a racemic mixture. Optical isomers of the Cyclo(hetero)alkenyl Compounds can be obtained by known techniques such as chiral chromatography or formation of diastereomeric salts from an optically active acid or base.


In addition, one or more hydrogen, carbon or other atoms of a Cyclo(hetero)alkenyl Compound can be replaced by an isotope of the hydrogen, carbon or other atoms. Such compounds, which are encompassed by the present invention, are useful as research and diagnostic tools in metabolism pharmacokinetic studies and in binding assays.


4.4 Therapeutic Uses of the Cyclo(Hetero)Alkenyl Compounds

In accordance with the invention, the Cyclo(hetero)alkenyl Compounds are administered to an animal in need of treatment or prevention of a Condition.


In one embodiment, an effective amount of a Cyclo(hetero)alkenyl Compound can be used to treat or prevent any condition treatable or preventable by inhibiting VR1. Examples of conditions that are treatable or preventable by inhibiting VR1 include, but are not limited to, pain, UI, an ulcer, IBD, and IBS.


In another embodiment, an effective amount of a Cyclo(hetero)alkenyl Compound can be used to treat or prevent any condition treatable or preventable by inhibiting mGluR5. Examples of conditions that are treatable or preventable by inhibiting mGluR5 include, but are not limited to, pain, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, a pruritic condition, and psychosis.


In another embodiment, an effective amount of a Cyclo(hetero)alkenyl Compound can be used to treat or prevent any condition treatable or preventable by inhibiting mGluR1. Examples of conditions that are treatable or preventable by inhibiting mGluR1 include, but are not limited to, pain, UI, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, and depression.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent acute or chronic pain. Examples of pain treatable or preventable using the Cyclo(hetero)alkenyl Compounds include, but are not limited to, cancer pain, labor pain, myocardial infarction pain, pancreatic pain, colic pain, post-operative pain, headache pain, muscle pain, arthritic pain, and pain associated with a periodontal disease, including gingivitis and periodontitis.


The Cyclo(hetero)alkenyl Compounds can also be used for treating or preventing pain associated with inflammation or with an inflammatory disease in an animal. Such pain can arise where there is an inflammation of the body tissue which can be a local inflammatory response and/or a systemic inflammation. For example, the Cyclo(hetero)alkenyl Compounds can be used to treat or prevent pain associated with inflammatory diseases including, but not limited to: organ transplant rejection; reoxygenation injury resulting from organ transplantation (see Grupp et al., J. Mol. Cell. Cardiol. 31:297-303 (1999)) including, but not limited to, transplantation of the heart, lung, liver, or kidney; chronic inflammatory diseases of the joints, including arthritis, rheumatoid arthritis, osteoarthritis and bone diseases associated with increased bone resorption; inflammatory lung diseases, such as asthma, adult respiratory distress syndrome, and chronic obstructive airway disease; inflammatory diseases of the eye, including corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis and endophthalmitis; chronic inflammatory diseases of the gum, including gingivitis and periodontitis; tuberculosis; leprosy; inflammatory diseases of the kidney, including uremic complications, glomerulonephritis and nephrosis; inflammatory diseases of the skin, including sclerodermatitis, psoriasis and eczema; inflammatory diseases of the central nervous system, including chronic demyelinating diseases of the nervous system, multiple sclerosis, AIDS-related neurodegeneration and Alzheimer s disease, infectious meningitis, encephalomyelitis, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and viral or autoimmune encephalitis; autoimmune diseases, including Type I and Type II diabetes mellitus; diabetic complications, including, but not limited to, diabetic cataract, glaucoma, retinopathy, nephropathy (such as microaluminuria and progressive diabetic nephropathy), polyneuropathy, mononeuropathies, autonomic neuropathy, gangrene of the feet, atherosclerotic coronary arterial disease, peripheral arterial disease, nonketotic hyperglycemic-hyperosmolar coma, foot ulcers, joint problems, and a skin or mucous membrane complication (such as an infection, a shin spot, a candidal infection or necrobiosis lipoidica diabeticorum); immune-complex vasculitis, and systemic lupus erythematosus (SLE); inflammatory diseases of the heart, such as cardiomyopathy, ischemic heart disease hypercholesterolemia, and atherosclerosis; as well as various other diseases that can have significant inflammatory components, including preeclampsia, chronic liver failure, brain and spinal cord trauma, and cancer. The Cyclo(hetero)alkenyl Compounds can also be used for treating or preventing pain associated with inflammatory disease that can, for example, be a systemic inflammation of the body, exemplified by gram-positive or gram negative shock, hemorrhagic or anaphylactic shock, or shock induced by cancer chemotherapy in response to pro-inflammatory cytokines, e.g., shock associated with pro-inflammatory cytokines. Such shock can be induced, e.g., by a chemotherapeutic agent that is administered as a treatment for cancer.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent UI. Examples of UI treatable or preventable using the Cyclo(hetero)alkenyl Compounds include, but are not limited to, urge incontinence, stress incontinence, overflow incontinence, neurogenic incontinence, and total incontinence.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent an ulcer. Examples of ulcers treatable or preventable using the Cyclo(hetero)alkenyl Compounds include, but are not limited to, a duodenal ulcer, a gastric ulcer, a marginal ulcer, an esophageal ulcer, or a stress ulcer.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent IBD, including Crohn's disease and ulcerative colitis.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent IBS. Examples of IBS treatable or preventable using the Cyclo(hetero)alkenyl Compounds include, but are not limited to, spastic-colon-type IBS and constipation-predominant IBS.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent an addictive disorder, including but not limited to, an eating disorder, an impulse-control disorder, an alcohol-related disorder, a nicotine-related disorder, an amphetamine-related disorder, a cannabis-related disorder, a cocaine-related disorder, an hallucinogen-related disorder, an inhalant-related disorders, and an opioid-related disorder, all of which are further sub-classified as listed below.


Eating disorders include, but are not limited to, Bulimia Nervosa, Nonpurging Type; Bulimia Nervosa, Purging Type; Anorexia; and Eating Disorder not otherwise specified (NOS).


Impulse control disorders include, but are not limited to, Intermittent Explosive Disorder, Kleptomania, Pyromania, Pathological Gambling, Trichotillomania, and Impulse Control Disorder not otherwise specified (NOS).


Alcohol-related disorders include, but are not limited to, Alcohol-Induced Psychotic Disorder with delusions, Alcohol Abuse, Alcohol Intoxication, Alcohol Withdrawal, Alcohol Intoxication Delirium, Alcohol Withdrawal Delirium, Alcohol-Induced Persisting Dementia, Alcohol-Induced Persisting Amnestic Disorder, Alcohol Dependence, Alcohol-Induced Psychotic Disorder with hallucinations, Alcohol-Induced Mood Disorder, Alcohol-Induced Anxiety Disorder, Alcohol-Induced Sexual Dysfunction, Alcohol-Induced Sleep Disorder, and Alcohol-Related Disorder not otherwise specified (NOS).


Nicotine-related disorders include, but are not limited to, Nicotine Dependence, Nicotine Withdrawal, and Nicotine-Related Disorder not otherwise specified (NOS).


Amphetamine-related disorders include, but are not limited to, Amphetamine Dependence, Amphetamine Abuse, Amphetamine Intoxication, Amphetamine Withdrawal, Amphetamine Intoxication Delirium, Amphetamine-Induced Psychotic Disorder with delusions, Amphetamine-Induced Psychotic Disorders with hallucinations, Amphetamine-Induced Mood Disorder, Amphetamine-Induced Anxiety Disorder, Amphetamine-Induced Sexual Dysfunction, Amphetamine-Induced Sleep Disorder, Amphetamine Related Disorder not otherwise specified (NOS), Amphetamine Intoxication, and Amphetamine Withdrawal.



Cannabis-related disorders include, but are not limited to, Cannabis Dependence, Cannabis Abuse, Cannabis Intoxication, Cannabis Intoxication Delirium, Cannabis-Induced Psychotic Disorder with delusions, Cannabis-Induced Psychotic Disorder with hallucinations, Cannabis-Induced Anxiety Disorder, Cannabis Related Disorder not otherwise specified (NOS), and Cannabis Intoxication.


Cocaine-related disorders include, but are not limited to, Cocaine Dependence, Cocaine Abuse, Cocaine Intoxication, Cocaine Withdrawal, Cocaine Intoxication Delirium, Cocaine-Induced Psychotic Disorder with delusions, Cocaine-Induced Psychotic Disorders with hallucinations, Cocaine-Induced Mood Disorder, Cocaine-Induced Anxiety Disorder, Cocaine-Induced Sexual Dysfunction, Cocaine-Induced Sleep Disorder, Cocaine Related Disorder not otherwise specified (NOS), Cocaine Intoxication, and Cocaine Withdrawal.


Hallucinogen-related disorders include, but are not limited to, Hallucinogen Dependence, Hallucinogen Abuse, Hallucinogen Intoxication, Hallucinogen Withdrawal, Hallucinogen Intoxication Delirium, Hallucinogen-Induced Psychotic Disorder with delusions, Hallucinogen-Induced Psychotic Disorders with hallucinations, Hallucinogen-Induced Mood Disorder, Hallucinogen-Induced Anxiety Disorder, Hallucinogen-Induced Sexual Dysfunction, Hallucinogen-Induced Sleep Disorder, Hallucinogen Related Disorder not otherwise specified (NOS), Hallucinogen Intoxication, and Hallucinogen Persisting Perception Disorder (Flashbacks).


Inhalant-related disorders include, but are not limited to, Inhalant Dependence, Inhalant Abuse, Inhalant Intoxication, Inhalant Intoxication Delirium, Inhalant-Induced Psychotic Disorder with delusions, Inhalant-Induced Psychotic Disorder with hallucinations, Inhalant-Induced Anxiety Disorder, Inhalant Related Disorder not otherwise specified (NOS), and Inhalant Intoxication.


Opioid-related disorders include, but are not limited to, Opioid Dependence, Opioid Abuse, Opioid Intoxication, Opioid Intoxication Delirium, Opioid-Induced Psychotic Disorder with delusions, Opioid-Induced Psychotic Disorder with hallucinations, Opioid-Induced Anxiety Disorder, Opioid Related Disorder not otherwise specified (NOS), Opioid Intoxication, and Opioid Withdrawal.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent Parkinson's disease and parkinsonism and the symptoms associated with Parkinson's disease and parkinsonism, including but not limited to, bradykinesia, muscular rigidity, resting tremor, and impairment of postural balance.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent generalized anxiety or severe anxiety and the symptoms associated with anxiety, including but not limited to, restlessness; tension; tachycardia; dyspnea; depression, including chronic “neurotic” depression; panic disorder; agoraphobia and other specific phobias; eating disorders; and personality disorders.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent epilepsy, including but not limited to, partial epilepsy, generalized epilepsy, and the symptoms associated with epilepsy, including but not limited to, simple partial seizures, jacksonian seizures, complex partial (psychomotor) seizures, convulsive seizures (grand mal or tonic-clonic seizures), petit mal (absence) seizures, and status epilepticus.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent strokes, including but not limited to, ischemic strokes and hemorrhagic strokes.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent a seizure, including but not limited to, infantile spasms, febrile seizures, and epileptic seizures.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent a pruritic condition, including but not limited to, pruritus caused by dry skin, scabies, dermatitis, herpetiformis, atopic dermatitis, pruritus vulvae et ani, miliaria, insect bites, pediculosis, contact dermatitis, drug reactions, urticaria, urticarial eruptions of pregnancy, psoriasis, lichen planus, lichen simplex chronicus, exfoliative dermatitis, folliculitis, bullous pemphigoid, or fiberglass dermatitis.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent psychosis, including but not limited to, schizophrenia, including paranoid schizophrenia, hebephrenic or disorganized schizophrenia, catatonic schizophrenia, undifferentiated schizophrenia, negative or deficit subtype schizophrenia, and non-deficit schizophrenia; a delusional disorder, including erotomanic subtype delusional disorder, grandiose subtype delusional disorder, jealous subtype delusional disorder, persecutory subtype delusional disorder, and somatic subtype delusional disorder; and brief psychosis.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent a cognitive disorder, including but not limited to, delirium and dementia such as multi-infarct dementia, dementia pugilistica, dementia caused by AIDS, and dementia caused by Alzheimer's disease.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent a memory deficiency, including but not limited to, dissociative amnesia and dissociative fugue.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent restricted brain function, including but not limited to, that caused by surgery or an organ transplant, restricted blood supply to the brain, a spinal cord injury, a head injury, hypoxia, cardiac arrest, or hypoglycemia.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent Huntington's chorea.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent ALS.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent retinopathy, including but not limited to, arteriosclerotic retinopathy, diabetic arteriosclerotic retinopathy, hypertensive retinopathy, non-proliferative retinopathy, and proliferative retinopathy.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent a muscle spasm.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent a migraine.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent vomiting, including but not limited to, nausea vomiting, dry vomiting (retching), and regurgitation.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent dyskinesia, including but not limited to, tardive dyskinesia and biliary dyskinesia.


The Cyclo(hetero)alkenyl Compounds can be used to treat or prevent depression, including but not limited to, major depression and bipolar disorder.


Applicants believe that the Cyclo(hetero)alkenyl Compounds are antagonists for VR1.


The invention relates to methods for inhibiting VR1 function in a cell comprising contacting a cell capable of expressing VR1 with an effective amount of a Cyclo(hetero)alkenyl Compound. This method can be used in vitro, for example, as an assay to select cells that express VR1 and, accordingly, are useful as part of an assay to select compounds useful for treating or preventing pain, UI, an ulcer, IBD, or IBS. The method is also useful for inhibiting VR1 function in a cell in vivo, in an animal, a human in one embodiment, by contacting a cell, in an animal, with an effective amount of a Cyclo(hetero)alkenyl Compound. In one embodiment, the method is useful for treating or preventing pain in an animal. In another embodiment, the method is useful for treating or preventing UI in an animal. In another embodiment, the method is useful for treating or preventing an ulcer in an animal. In another embodiment, the method is useful for treating or preventing IBD in an animal. In another embodiment, the method is useful for treating or preventing IBS in an animal.


Examples of tissue comprising cells capable of expressing VR1 include, but are not limited to, neuronal, brain, kidney, urothelium, and bladder tissue. Methods for assaying cells that express VR1 are known in the art.


Applicants believe that the Cyclo(hetero)alkenyl Compounds are antagonists for mGluR5.


The invention relates to methods for inhibiting mGluR5 function in a cell comprising contacting a cell capable of expressing mGluR5 with an amount of a Cyclo(hetero)alkenyl Compound effective to inhibit mGluR5 function in the cell. This method can be used in vitro, for example, as an assay to select cells that express mGluR5 and, accordingly, are useful as part of an assay to select compounds useful for treating or preventing pain, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, a pruritic condition, or psychosis. The method is also useful for inhibiting mGluR5 function in a cell in vivo, in an animal, a human in one embodiment, by contacting a cell, in an animal, with an amount of a Cyclo(hetero)alkenyl Compound effective to inhibit mGluR5 function in the cell. In one embodiment, the method is useful for treating or preventing pain in an animal in need thereof. In another embodiment, the method is useful for treating or preventing an addictive disorder in an animal in need thereof. In another embodiment, the method is useful for treating or preventing Parkinson's disease in an animal in need thereof. In another embodiment, the method is useful for treating or preventing parkinsonism in an animal in need thereof. In another embodiment, the method is useful for treating or preventing anxiety in an animal in need thereof. In another embodiment, the method is useful for treating or preventing a pruritic condition in an animal in need thereof. In another embodiment, the method is useful for treating or preventing psychosis in an animal in need thereof.


Examples of cells capable of expressing mGluR5 are neuronal and glial cells of the central nervous system, particularly the brain, especially in the nucleus accumbens. Methods for assaying cells that express mGluR5 are known in the art.


Applicants believe that the Cyclo(hetero)alkenyl Compounds are antagonists for mGluR1.


The invention relates to methods for inhibiting mGluR1 function in a cell comprising contacting a cell capable of expressing mGluR1 with an amount of a Cyclo(hetero)alkenyl Compound effective to inhibit mGluR1 function in the cell. This method can be used in vitro, for example, as an assay to select cells that express mGluR1 and, accordingly, are useful as part of an assay to select compounds useful for treating or preventing pain, UI, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression. The method is also useful for inhibiting mGluR1 function in a cell in vivo, in an animal, a human in one embodiment, by contacting a cell, in an animal, with an amount of a Cyclo(hetero)alkenyl Compound effective to inhibit mGluR1 function in the cell. In one embodiment, the method is useful for treating or preventing pain in an animal in need thereof. In another embodiment, the method is useful for treating or preventing UI in an animal in need thereof. In another embodiment, the method is useful for treating or preventing an addictive disorder in an animal in need thereof. In another embodiment, the method is useful for treating or preventing Parkinson's disease in an animal in need thereof. In another embodiment, the method is useful for treating or preventing parkinsonism in an animal in need thereof. In another embodiment, the method is useful for treating or preventing anxiety in an animal in need thereof. In another embodiment, the method is useful for treating or preventing epilepsy in an animal in need thereof. In another embodiment, the method is useful for treating or preventing stroke in an animal in need thereof. In another embodiment, the method is useful for treating or preventing a seizure in an animal in need thereof. In another embodiment, the method is useful for treating or preventing a pruritic condition in an animal in need thereof. In another embodiment, the method is useful for treating or preventing psychosis in an animal in need thereof. In another embodiment, the method is useful for treating or preventing a cognitive disorder in an animal in need thereof. In another embodiment, the method is useful for treating or preventing a memory deficit in an animal in need thereof. In another embodiment, the method is useful for treating or preventing restricted brain function in an animal in need thereof. In another embodiment, the method is useful for treating or preventing Huntington's chorea in an animal in need thereof. In another embodiment, the method is useful for treating or preventing ALS in an animal in need thereof. In another embodiment, the method is useful for treating or preventing dementia in an animal in need thereof. In another embodiment, the method is useful for treating or preventing retinopathy in an animal in need thereof. In another embodiment, the method is useful for treating or preventing a muscle spasm in an animal in need thereof. In another embodiment, the method is useful for treating or preventing a migraine in an animal in need thereof. In another embodiment, the method is useful for treating or preventing vomiting in an animal in need thereof. In another embodiment, the method is useful for treating or preventing dyskinesia in an animal in need thereof. In another embodiment, the method is useful for treating or preventing depression in an animal in need thereof.


Examples of cells capable of expressing mGluR1 include, but are not limited to, cerebellar Purkinje neuron cells, Purkinje cell bodies (punctate), cells of spine(s) of the cerebellum; neurons and neurophil cells of olfactory-bulb glomeruli; cells of the superficial layer of the cerebral cortex; hippocampus cells; thalamus cells; superior colliculus cells; and spinal trigeminal nucleus cells. Methods for assaying cells that express mGluR1 are known in the art.


4.5 Therapeutic/Prophylactic Administration and Compositions of the Invention

Due to their activity, the Cyclo(hetero)alkenyl Compounds are advantageously useful in veterinary and human medicine. As described above, the Cyclo(hetero)alkenyl Compounds are useful for treating or preventing a condition in an animal in need thereof.


When administered to an animal, the Cyclo(hetero)alkenyl Compounds are administered as a component of a composition that comprises a pharmaceutically acceptable carrier or excipient. The present compositions, which comprise a Cyclo(hetero)alkenyl Compound, can be administered orally. The Cyclo(hetero)alkenyl Compounds of the invention can also be administered by any other convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral, rectal, and intestinal mucosa, etc.) and can be administered together with another therapeutically active agent. Administration can be systemic or local. Various delivery systems are known, e.g., encapsulation in liposomes, microparticles, microcapsules, capsules, etc., and can be used to administer the Cyclo(hetero)alkenyl Compound.


Methods of administration include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intracerebral, intravaginal, transdermal, rectal, by inhalation, or topical, particularly to the ears, nose, eyes, or skin. The mode of administration is left to the discretion of the practitioner. In most instances, administration will result in the release of the Cyclo(hetero)alkenyl Compounds into the bloodstream.


In specific embodiments, it can be desirable to administer the Cyclo(hetero)alkenyl Compounds locally. This can be achieved, for example, and not by way of limitation, by local infusion during surgery, topical application, e.g., in conjunction with a wound dressing after surgery, by injection, by means of a catheter, by means of a suppository or enema, or by means of an implant, said implant being of a porous, non-porous, or gelatinous material, including membranes, such as sialastic membranes, or fibers.


In certain embodiments, it can be desirable to introduce the Cyclo(hetero)alkenyl Compounds into the central nervous system or gastrointestinal tract by any suitable route, including intraventricular, intrathecal, and epidural injection, and enema. Intraventricular injection can be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Ommaya reservoir.


Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent, or via perfusion in a fluorocarbon or synthetic pulmonary surfactant. In certain embodiments, the Cyclo(hetero)alkenyl Compounds can be formulated as a suppository, with traditional binders and excipients such as triglycerides.


In another embodiment, the Cyclo(hetero)alkenyl Compounds can be delivered in a vesicle, in particular a liposome (see Langer, Sci. 249:1527-1533 (1990) and Treat et al., Liposomes in the Therapy of Infectious Disease and Cancer 317-327 and 353-365 (1989)).


In yet another embodiment, the Cyclo(hetero)alkenyl Compounds can be delivered in a controlled-release system or sustained-release system (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984)). Other controlled- or sustained-release systems discussed in the review by Langer, Sci. 249:1527-1533 (1990) can be used. In one embodiment, a pump can be used (Langer, Sci. 249:1527-1533 (1990); Sefton, CRC Crit. Ref Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); and Saudek et al., N. Engl. J. Med. 321:574 (1989)). In another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release (Langer and Wise eds., 1974); Controlled Drug Bioavailability, Drug Product Design and Performance (Smolen and Ball eds., 1984); Ranger and Peppas, J. Macromol. Sci. Rev. Macromol. Chem. 23:61 (1983); Levy et al., Sci. 228:190 (1985); During et al., Ann. Neurol. 25:351 (1989); and Howard et al., J. Neurosurg. 71:105 (1989)). In yet another embodiment, a controlled- or sustained-release system can be placed in proximity of a target of the Cyclo(hetero)alkenyl Compounds, e.g., the spinal column, brain, or gastrointestinal tract, thus requiring only a fraction of the systemic dose.


The present compositions can optionally comprise a suitable amount of a pharmaceutically acceptable excipient so as to provide the form for proper administration to the animal.


Such pharmaceutical excipients can be liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The pharmaceutical excipients can be saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea and the like. In addition, auxiliary, stabilizing, thickening, lubricating, and coloring agents can be used. In one embodiment, the pharmaceutically acceptable excipients are sterile when administered to an animal. Water is a particularly useful excipient when the Cyclo(hetero)alkenyl Compound is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid excipients, particularly for injectable solutions. Suitable pharmaceutical excipients also include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The present compositions, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents.


The present compositions can take the form of solutions, suspensions, emulsions, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, aerosols, sprays, suspensions, or any other form suitable for use. In one embodiment, the composition is in the form of a capsule (see e.g., U.S. Pat. No. 5,698,155). Other examples of suitable pharmaceutical excipients are described in Remington's Pharmaceutical Sci. 1447-1676 (Alfonso R. Gennaro ed., 19th ed. 1995), incorporated herein by reference.


In one embodiment, the Cyclo(hetero)alkenyl Compounds are formulated in accordance with routine procedures as a composition adapted for oral administration to human beings. Compositions for oral delivery can be in the form of tablets, lozenges, aqueous or oily suspensions, granules, powders, emulsions, capsules, syrups, or elixirs, for example. Orally administered compositions can contain one or more agents, for example, sweetening agents such as fructose, aspartame or saccharin; flavoring agents such as peppermint, oil of wintergreen, or cherry; coloring agents; and preserving agents, to provide a pharmaceutically palatable preparation. Moreover, where in tablet or pill form, the compositions can be coated to delay disintegration and absorption in the gastrointestinal tract thereby providing a sustained action over an extended period of time. Selectively permeable membranes surrounding an osmotically active driving compound are also suitable for orally administered compositions. In these latter platforms, fluid from the environment surrounding the capsule is imbibed by the driving compound, which swells to displace the agent or agent composition through an aperture. These delivery platforms can provide an essentially zero order delivery profile as opposed to the spiked profiles of immediate release formulations. A time-delay material such as glycerol monostearate or glycerol stearate can also be used. Oral compositions can include standard excipients such as mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, and magnesium carbonate. In one embodiment, the excipients are of pharmaceutical grade.


In another embodiment, the Cyclo(hetero)alkenyl Compounds can be formulated for intravenous administration. Typically, compositions for intravenous administration comprise sterile isotonic aqueous buffer. Where necessary, the compositions can also include a solubilizing agent. Compositions for intravenous administration can optionally include a local anesthetic such as lidocaine to lessen pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampule or sachette indicating the quantity of active agent. Where the Cyclo(hetero)alkenyl Compounds are to be administered by infusion, they can be dispensed, for example, with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the Cyclo(hetero)alkenyl Compounds are administered by injection, an ampule of sterile water for injection or saline can be provided so that the ingredients can be mixed prior to administration.


The Cyclo(hetero)alkenyl Compounds can be administered by controlled-release or sustained-release means or by delivery devices that are known to those of ordinary skill in the art. Examples include, but are not limited to, those described in U.S. Pat. Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,556; and 5,733,566, each of which is incorporated herein by reference. Such dosage forms can be used to provide controlled- or sustained-release of one or more active ingredients using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, microspheres, or a combination thereof to provide the desired release profile in varying proportions. Suitable controlled- or sustained-release formulations known to those of ordinary skill in the art, including those described herein, can be readily selected for use with the active ingredients of the invention. The invention thus encompasses single unit dosage forms suitable for oral administration such as, but not limited to, tablets, capsules, gelcaps, and caplets that are adapted for controlled- or sustained-release.


Controlled- or sustained-release pharmaceutical compositions can have a common goal of improving drug therapy over that achieved by their non-controlled or non-sustained counterparts. In one embodiment, a controlled- or sustained-release composition comprises a minimal amount of a Cyclo(hetero)alkenyl Compound to cure or control the condition in a minimum amount of time. Advantages of controlled- or sustained-release compositions include extended activity of the drug, reduced dosage frequency, and increased patient compliance. In addition, controlled- or sustained-release compositions can favorably affect the time of onset of action or other characteristics, such as blood levels of the Cyclo(hetero)alkenyl Compound, and can thus reduce the occurrence of adverse side effects.


Controlled- or sustained-release compositions can initially release an amount of a Cyclo(hetero)alkenyl Compound that promptly produces the desired therapeutic or prophylactic effect, and gradually and continually release other amounts of the Cyclo(hetero)alkenyl Compound to maintain this level of therapeutic or prophylactic effect over an extended period of time. To maintain a constant level of the Cyclo(hetero)alkenyl Compound in the body, the Cyclo(hetero)alkenyl Compound can be released from the dosage form at a rate that will replace the amount of Cyclo(hetero)alkenyl Compound being metabolized and excreted from the body. Controlled- or sustained-release of an active ingredient can be stimulated by various conditions, including but not limited to, changes in pH, changes in temperature, concentration or availability of enzymes, concentration or availability of water, or other physiological conditions or compounds.


In another embodiment, a composition is prepared by admixing a Cyclo(hetero)alkenyl Compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient. Admixing can be accomplished using methods known for admixing a compound (or a salt) and a pharmaceutically acceptable carrier or excipient. In another embodiment, the Cyclo(hetero)alkenyl Compound or a pharmaceutically acceptable salt thereof is present in an effective amount.


The amount of the Cyclo(hetero)alkenyl Compound that is effective in the treatment or prevention of a condition can be determined by standard clinical techniques. In addition, in vitro or in vivo assays can optionally be employed to help identify optimal dosage ranges. The precise dose to be employed will also depend on the route of administration, and the seriousness of the Condition and can be decided according to the judgment of a practitioner and/or each animal's circumstances. Suitable effective dosage amounts, however, range from about 0.01 mg/kg of body weight to about 2500 mg/kg of body weight, although they are typically about 100 mg/kg of body weight or less. In one embodiment, the effective dosage amount ranges from about 0.01 mg/kg of body weight to about 100 mg/kg of body weight of a Cyclo(hetero)alkenyl Compound, in another embodiment, about 0.02 mg/kg of body weight to about 50 mg/kg of body weight, and in another embodiment, about 0.025 mg/kg of body weight to about 20 mg/kg of body weight. In one embodiment, an effective dosage amount is administered about every 24 h until the Condition is abated. In another embodiment, an effective dosage amount is administered about every 12 h until the Condition is abated. In another embodiment, an effective dosage amount is administered about every 8 h until the Condition is abated. In another embodiment, an effective dosage amount is administered about every 6 h until the Condition is abated. In another embodiment, an effective dosage amount is administered about every 4 h until the Condition is abated. The effective dosage amounts described herein refer to total amounts administered; that is, if more than one Cyclo(hetero)alkenyl Compound is administered, the effective dosage amounts correspond to the total amount administered.


Where a cell capable of expressing VR1, mGluR5 or mGluR1 is contacted with a Cyclo(hetero)alkenyl Compound in vitro, the amount effective for inhibiting the VR1, mGluR5 or mGluR1 receptor function in a cell will typically range from about 0.01 μg/L to about 5 mg/L, in one embodiment, from about 0.01 μg/L to about 2.5 mg/L, in another embodiment, from about 0.01 μg/L to about 0.5 mg/L, and in another embodiment, from about 0.01 μg/L to about 0.25 mg/L of a solution or suspension of a pharmaceutically acceptable carrier or excipient. In one embodiment, the volume of solution or suspension comprising the Cyclo(hetero)alkenyl Compound is from about 0.01 μL to about 1 mL. In another embodiment, the volume of solution or suspension is about 200 μL.


Where a cell capable of expressing VR1, mGluR5, or mGluR1 is contacted with a Cyclo(hetero)alkenyl Compound in vivo, the amount effective for inhibiting the receptor function in a cell will typically range from about 0.01 mg/kg of body weight to about 100 mg/kg of body weight, although it typically ranges from about 100 mg/kg of body weight or less. In one embodiment, the effective dosage amount ranges from about 0.01 mg/kg of body weight to about 100 mg/kg of body weight of a Cyclo(hetero)alkenyl Compound, in another embodiment, about 0.020 mg/kg of body weight to about 50 mg/kg of body weight, and in another embodiment, about 0.025 mg/kg of body weight to about 20 mg/kg of body weight. In one embodiment, an effective dosage amount is administered about every 24 h. In another embodiment, an effective dosage amount is administered about every 12 h. In another embodiment, an effective dosage amount is administered about every 8 h. In another embodiment, an effective dosage amount is administered about every 6 h. In another embodiment, an effective dosage amount is administered about every 4 h.


The Cyclo(hetero)alkenyl Compounds can be assayed in vitro or in vivo for the desired therapeutic or prophylactic activity prior to use in humans. Animal model systems can be used to demonstrate safety and efficacy.


The present methods for treating or preventing a Condition in an animal in need thereof can further comprise administering another therapeutic agent to the animal being administered a Cyclo(hetero)alkenyl Compound. In one embodiment, the other therapeutic agent is administered in an effective amount.


The present methods for inhibiting VR1 function in a cell capable of expressing VR1 can further comprise contacting the cell with an effective amount of another therapeutic agent.


The present methods for inhibiting mGluR5 function in a cell capable of expressing mGluR5 can further comprise contacting the cell with an effective amount of another therapeutic agent.


The present methods for inhibiting mGluR1 function in a cell capable of expressing mGluR1 can further comprise contacting the cell with an effective amount of another therapeutic agent.


Effective amounts of the other therapeutic agents are known to those skilled in the art. However, it is well within the skilled artisan's purview to determine the other therapeutic agent's optimal effective-amount range. In one embodiment of the invention, where another therapeutic agent is administered to an animal, the effective amount of the Cyclo(hetero)alkenyl Compound is less than its effective amount would be where the other therapeutic agent is not administered. In this case, without being bound by theory, it is believed that the Cyclo(hetero)alkenyl Compounds and the other therapeutic agent act synergistically to treat or prevent a Condition.


The other therapeutic agent can be, but is not limited to, an opioid agonist, a non-opioid analgesic, a non-steroidal anti-inflammatory agent, an antimigraine agent, a Cox-II inhibitor, an antiemetic, a β-adrenergic blocker, an anticonvulsant, an antidepressant, a Ca2+-channel blocker, an anticancer agent, an agent for treating or preventing UI, an agent for treating or preventing an ulcer, an agent for treating or preventing IBD, an agent for treating or preventing IBS, an agent for treating addictive disorder, an agent for treating Parkinson's disease and parkinsonism, an agent for treating anxiety, an agent for treating epilepsy, an agent for treating a stroke, an agent for treating a seizure, an agent for treating a pruritic condition, an agent for treating psychosis, an agent for treating Huntington's chorea, an agent for treating ALS, an agent for treating a cognitive disorder, an agent for treating a migraine, an agent for treating vomiting, an agent for treating dyskinesia, or an agent for treating depression, and mixtures thereof.


Examples of useful opioid agonists include, but are not limited to, alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papavereturn, pentazocine, phenadoxone, phenomorphan, phenazocine, phennneridine, piminndine, piritramide, prnheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts thereof, and mixtures thereof.


In certain embodiments, the opioid agonist is selected from codeine, hydromorphone, hydrocodone, oxycodone, dihydrocodeine, dihydromorphine, morphine, tramadol, oxymorphone, pharmaceutically acceptable salts thereof, and mixtures thereof.


Examples of useful non-opioid analgesics include non-steroidal anti-inflammatory agents, such as aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid, tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam, isoxicam, and pharmaceutically acceptable salts thereof, and mixtures thereof. Other suitable non-opioid analgesics include the following, non-limiting, chemical classes of analgesic, antipyretic, nonsteroidal anti-inflammatory drugs: salicylic acid derivatives, including aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salicylsalicylic acid, sulfasalazine, and olsalazin; para-aminophenol derivatives including acetaminophen and phenacetin; indole and indene acetic acids, including indomethacin, sulindac, and etodolac; heteroaryl acetic acids, including tolmetin, diclofenac, and ketorolac; anthranilic acids (fenamates), including mefenamic acid and meclofenamic acid; enolic acids, including oxicams (piroxicam, tenoxicam), and pyrazolidinediones (phenylbutazone, oxyphenthartazone); and alkanones, including nabumetone. For a more detailed description of the NSAIDs, see Paul A. Insel, Analgesic-Antipyretic and Anti-inflammatory Agents and Drugs Employed in the Treatment of Gout, in Goodman & Gilman's The Pharmacological Basis of Therapeutics 617-57 (Perry B. Molinhoff and Raymond W. Ruddon eds., 9th ed 1996) and Glen R. Hanson, Analgesic, Antipyretic and Anti-Inflammatory Drugs in Remington: The Science and Practice of Pharmacy Vol II 1196-1221 (A. R. Gennaro ed. 19th ed. 1995) which are hereby incorporated by reference in their entireties.


Examples of useful Cox-II inhibitors and 5-lipoxygenase inhibitors, as well as combinations thereof, are described in U.S. Pat. No. 6,136,839, which is hereby incorporated by reference in its entirety. Examples of useful Cox-II inhihitors include, but are not limited to, rofecoxib and celecoxib.


Examples of useful antimigraine agents include, but are not limited to, alpiropride, bromocriptine, dihydroergotamine, dolasetron, ergocornine, ergocorninine, ergocryptine, ergonovine, ergot, ergotamine, flumedroxone acetate, fonazine, ketanserin, lisuride, lomerizine, methylergonovine, methysergide, metoprolol, naratriptan, oxetorone, pizotyline, propranolol, risperidone, rizatriptan, sumatriptan, timolol, trazodone, zolmitriptan, and mixtures thereof.


The other therapeutic agent can alternatively be an agent useful for reducing any potential side effects of a Cyclo(hetero)alkenyl Compounds. For example, the other therapeutic agent can be an antiemetic agent. Examples of useful antiemetic agents include, but are not limited to, metoclopromide, domperidone, prochlorperazine, promethazine, chlorpromazine, trimethobenzamide, odansteron, granisetron, hydroxyzine, acetylleucine monoethanolamine, alizapride, azasetron, benzquinamide, bietanautine, bromopride, buclizine, clebopride, cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone, oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol, thiethylperazine, thioproperazine, tropisetron, and mixtures thereof.


Examples of useful β-adrenergic blockers include, but are not limited to, acebutolol, alprenolol, amosulabol, arotinolol, atenolol, befunolol, betaxolol, bevantolol, bisoprolol, bopindolol, bucumolol, bufetolol, bufuralol, bunitrolol, bupranolol, butidrine hydrochloride, butofilolol, carazolol, carteolol, carvedilol, celiprolol, cetamolol, cloranolol, dilevalol, epanolol, esmolol, indenolol, labetalol, levobunolol, mepindolol, metipranolol, metoprolol, moprolol, nadolol, nadoxolol, nebivalol, nifenalol, nipradilol, oxprenolol, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, sulfinalol, talinolol, tertatolol, tilisolol, timolol, toliprolol, and xibenolol.


Examples of useful anticonvulsants include, but are not limited to, acetylpheneturide, albutoin, aloxidone, aminoglutethimide, 4-amino-3-hydroxybutyric acid, atrolactamide, beclamide, buramate, calcium bromide, carbamazepine, cinromide, clomethiazole, clonazepam, decimemide, diethadione, dimethadione, doxenitroin, eterobarb, ethadione, ethosuximide, ethotoin, felbamate, fluoresone, gabapentin, 5-hydroxytryptophan, lamotrigine, magnesium bromide, magnesium sulfate, mephenyloin, mephobarbital, metharbital, methetoin, methsuximide, 5-methyl-5-(3-phenanthryl)-hydantoin, 3-methyl-5-phenylhydantoin, narcobarbital, nimetazepam, nitrazepam, oxcarbazepine, paramethadione, phenacemide, phenetharbital, pheneturide, phenobarbital, phensuximide, phenylmethylbarbituric acid, phenyloin, phethenylate sodium, potassium bromide, pregabaline, primidone, progabide, sodium bromide, solanum, strontium bromide, suclofenide, sulthiame, tetrantoin, tiagabine, topiramate, trimethadione, valproic acid, valpromide, vigabatrin, and zonisamide.


Examples of useful antidepressants include, but are not limited to, binedaline, caroxazone, citalopram, (S)-citalopram, dimethazan, fencamine, indalpine, indeloxazine hydrocholoride, nefopam, nomifensine, oxitriptan, oxypertine, paroxetine, sertraline, thiazesim, trazodone, benmoxine, iproclozide, iproniazid, isocarboxazid, nialamide, octamoxin, phenelzine, cotinine, rolicyprine, rolipram, maprotiline, metralindole, mianserin, mirtazepine, adinazolam, amitriptyline, amitriptylinoxide, amoxapine, butriptyline, clomipramine, demexiptiline, desipramine, dibenzepin, dimetacrine, dothiepin, doxepin, fluacizine, imipramine, imipramine N-oxide, iprindole, lofepramine, melitracen, metapramine, nortriptyline, noxiptilin, opipramol, pizotyline, propizepine, protriptyline, quinupramine, tianeptine, trimipramine, adrafinil, benactyzine, bupropion, butacetin, dioxadrol, duloxetine, etoperidone, febarbamate, femoxetine, fenpentadiol, fluoxetine, fluvoxamine, hematoporphyrin, hypericin, levophacetoperane, medifoxamine, milnacipran, minaprine, moclobemide, nefazodone, oxaflozane, piberaline, prolintane, pyrisuccideanol, ritanserin, roxindole, rubidium chloride, sulpiride, tandospirone, thozalinone, tofenacin, toloxatone, tranylcypromine, L-tryptophan, venlafaxine, viloxazine, and zimelidine.


Examples of useful Ca2+-channel blockers include, but are not limited to, bepridil, clentiazem, diltiazem, fendiline, gallopamil, mibefradil, prenylamine, semotiadil, terodiline, verapamil, amlodipine, aranidipine, barnidipine, benidipine, cilnidipine, efonidipine, elgodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, cinnarizine, flunarizine, lidoflazine, lomerizine, bencyclane, etafenone, fantofarone, and perhexyline.


Examples of useful anticancer agents include, but are not limited to, acivicin, aclarubicin, acodazole hydrochloride, acronine, adozelesin, aldesleukin, altretamine, amhmycin, ameptntrnn acetate, aminogutethimide, amsacrine, anastrozole, anthramycin, asparaginase, asperlin, azacitidine, azetepa, azotomycin, batimastat, benzodepa, bicalutamide, bisantrene hydrochloride, bisnafide dimesylate, bizelesin, bleomycin sulfate, brequinar sodium, bropirimine, busulfan, cactinomycin, calusterone, caracemide, carbetimer, carboplatin, carmustine, carubicin hydrochloride, carzelesin, cedefingol, chlorambucil, cirolemycin, cisplatin, cladribine, crisnatol mesylate, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin hydrochloride, decitabine, dexormaplatin, dezaguanine, dezaguanine mesylate, diaziquone, docetaxel, doxorubicin, doxorubicin hydrochloride, droloxifene, droloxifene citrate, dromostanolone propionate, duazomycin, edatrexate, eflornithine hydrochloride, elsamitrucin, enloplatin, enpromate, epipropidine, epirubicin hydrochloride, erbulozole, esorubicin hydrochloride, estramustine, estramustine phosphate sodium, etanidazole, etoposide, etoposide phosphate, etoprine, fadrozole hydrochloride, fazarabine, fenretinide, floxuridine, fludarabine phosphate, fluorouracil, fluorocitabine, fosquidone, fostriecin sodium, gemcitabine, gemcitabine hydrochloride, hydroxyurea, idarubicin hydrochloride, ifosfamide, ilmofosine, interleukin II (including recombinant interleukin II or rIL2), interferon alpha-2a, interferon alpha-2b, interferon alpha-n1, interferon alpha-n3, interferon beta-I a, interferon gamma-I b, iproplatin, irinotecan hydrochloride, lanreotide acetate, letrozole, leuprolide acetate, liarozole hydrochloride, lometrexol sodium, lomustine, losoxantrone hydrochloride, masoprocol, maytansine, mechlorethamine hydrochloride, megestrol acetate, melengestrol acetate, melphalan, menogaril, mercaptopurine, methotrexate, methotrexate sodium, metoprine, meturedepa, mitindomide, mitocarcin, mitocromin, mitogillin, mitomalcin, mitomycin, mitosper, mitotane, mitoxantrone hydrochloride, mycophenolic acid, nocodazole, nogalamycin, ormaplatin, oxisuran, paclitaxel, pegaspargase, peliomycin, pentamustine, peplomycin sulfate, perfosfamide, pipobroman, piposulfan, piroxantrone hydrochloride, plicamycin, plomestane, porfimer sodium, porfiromycin, prednimustine, procarbazine hydrochloride, puromycin, puromycin hydrochloride, pyrazofurin, riboprine, rogletimide, safingol, safingol hydrochloride, semustine, simtrazene, sparfosate sodium, sparsomycin, spirogermanium hydrochloride, spiromustine, spiroplatin, streptonigrin, streptozotocin, sulofenur, talisomycin, tecogalan sodium, tegafur, teloxantrone hydrochloride, temoporfin, teniposide, teroxirone, testolactone, thiamiprine, thioguanine, thiotepa, tiazofurin, tirapazamine, toremifene citrate, trestolone acetate, triciribine phosphate, trimetrexate, trimetrexate glucuronate, triptorelin, tubulnozole hydrochloride, uracil mustard, uredepa, vapreotide, verteporfin, vinblastine sulfate, vincristine sulfate, vindesine, vindesine sulfate, vinepidine sulfate, vinglycinate sulfate, vinleurosine sulfate, vinorelbine tartrate, vinrosidine sulfate, vinzolidine sulfate, vorozole, zeniplatin, zinostatin, zorubicin hydrochloride.


Examples of other anti-cancer drugs include, but are not limited to, 20-epi-1,25 dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; aclarubicin; acylfulvene; adecypenol; adozelesin; aldesleukin; ALL-TK antagonists; altretamine; ambamustine; amidox; amifostine; aminolevulinic acid; amrubicin; amsacrine; anagrelide; anastrozole; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-dorsalizing morphogenetic protein-1; antiandrogen, antiestrogen; antineoplaston; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators; apurinic acid; ara-CDP-DL-PTBA; arginine deaminase; asulacrine; atamestane; atrimustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin; azatyrosine; baccatin III derivatives; balanol; batimastat; BCR/ABL antagonists; benzochlorins; benzoylstaurosporine; beta lactam derivatives; beta-alethine; betaclamycin B; betulinic acid; bFGF inhibitor; bicalutamide; bisantrene; bisaziridinylspermine; bisnafide; bistratene A; bizelesin; breflate; bropirimine; budotitane; buthionine sulfoximine; calcipotriol; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carboxamide-amino-triazole; carboxyamidotriazole; CaRest M3; CARN 700; cartilage derived inhibitor; carzelesin; casein kinase inhibitors (ICOS); castanospermine; cecropin B; cetrorelix; chlorlns; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrin; cladribine; clomifene analogues; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogue; conagenin; crambescidin 816; crisnatol; cryptophycin 8; cryptophycin A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfate; cytolytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin; dexamethasone; dexifosfamide; dexrazoxane; dexverapamil; diaziquone; didemnin B; didox; diethylnorspermine; dihydro-5-azacytidine; dihydrotaxol, 9-; dioxamycin; diphenyl spiromustine; docetaxel; docosanol; dolasetron; doxifluridine; droloxifene; dronabinol; duocarmycin SA; ebselen; ecomustine; edelfosine; edrecolomab; eflornithine; elemene; emitefur; epirubicin; epristeride; estramustine analogue; estrogen agonists; estrogen antagonists; etanidazole; etoposide phosphate; exemestane; fadrozole; fazarabine; fenretinide; filgrastim; finasteride; flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunorunicin hydrochloride; forfenimex; formestane; fostriecin; fotemustine; gadolinium texaphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; hypericin; ibandronic acid; idarubicin; idoxifene; idramantone; ilmofosine; ilomastat; imidazoacridones; imiquimod; immunostimulant peptides; insulin-like growth factor-1 receptor inhibitor; interferon agonists; interferons; interleukins; iobenguane; iododoxorubicin; ipomeanol, 4-; iroplact; irsogladine; isobengazole; isohomohalicondrin B; itasetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; lenograstim; lentinan sulfate; leptolstatin; letrozole; leukemia inhibiting factor; leukocyte alpha interferon; leuprolide+estrogen+progesterone; leuprorelin; levamisole; liarozole; linear polyamine analogue; lipophilic disaccharide peptide; lipophilic platinum compounds; lissoclinamide 7; lobaplatin; lombricine; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lurtotecan; lutetium texaphyrin; lysofylline; lytic peptides; maitansine; mannostatin A; marimastat; masoprocol; maspin; matrilysin inhibitors; matrix metalloproteinase inhibitors; menogaril; merbarone; meterelin; methioninase; metoclopramide; MIF inhibitor; mifepristone; miltefosine; mirimostim; mismatched double stranded RNA; mitoguazone; mitolactol; mitomycin analogues; mitonafide; mitotoxin fibroblast growth factor-saporin; mitoxantrone; mofarotene; molgramostim; monoclonal antibody, human chorionic gonadotrophin; monophosphoryl lipid A+myobacterium cell wall sk; mopidamol; multiple drug resistance gene inhibitor; multiple tumor suppressor 1-based therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall extract; myriaporone; N-acetyldinaline; N-substituted benzamides; nafarelin; nagrestip; naloxone+pentazocine; napavin; naphterpin; nartograstim; nedaplatin; nemorubicin; neridronic acid; neutral endopeptidase; nilutamide; nisamycin; nitric oxide modulators; nitroxide antioxidant; nitrullyn; O6-benzylguanine; octreotide; okicenone; oligonucleotides; onapristone; odansteron; oracin; oral cytokine inducer; ormaplatin; osaterone; oxaliplatin; oxaunomycin; paclitaxel; paclitaxel analogues; paclitaxel derivatives; palauamine; palmitoylrhizoxin; pamidronic acid; panaxytriol; panomifene; parabactin; pazelliptine; pegaspargase; peldesine; pentosan polysulfate sodium; pentostatin; pentrozole; perflubron; perfosfamide; perillyl alcohol; phenazinomycin; phenylacetate; phosphatase inhibitors; picibanil; pilocarpine hydrochloride; pirarubicin; piritrexim; placetin A; placetin B; plasminogen activator inhibitor; platinum complex; platinum compounds; platinum-triamine complex; porfimer sodium; porfiromycin; prednisone; propyl bis-acridone; prostaglandin J2; proteasome inhibitors; protein A-based immune modulator; protein kinase C inhibitor; protein kinase C inhibitors, microalgal; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; purpurins; pyrazoloacridine; pyridoxylated hemoglobin polyoxyethylene conjugate; raf antagonists; raltitrexed; ramosetron; ras farnesyl protein transferase inhibitors; ras inhibitors; ras-GAP inhibitor; retelliptine demethylated; rhenium Re 186 etidronate; rhizoxin; ribozymes; R11 retinamide; rogletimide; rohitukine; romurtide; roquinimex; rubiginone B1; ruboxyl; safingol; saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 mimetics; semustine; senescence derived inhibitor 1; signal transduction inhibitors; signal transduction modulators; single chain antigen binding protein; sizofuran; sobuzoxane; sodium borocaptate; sodium phenylacetate; solverol; somatomedin binding protein; sonermin; sparfosic acid; spicamycin D; spiromustine; splenopentin; spongistatin 1; squalamine; stem cell inhibitor; stem-cell division inhibitors; stipiamide; stromelysin inhibitors; sulfinosine; superactive vasoactive intestinal peptide antagonist; suradista; suramin; swainsonine; synthetic glycosaminoglycans; tallimustine; tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; temoporfin; temozolomide; teniposide; tetrachlorodecaoxide; tetrazomine; thaliblastine; thiocoraline; thrombopoietin; thrombopoietin mimetic; thymalfasin; thymopoietin receptor agonist; thymotrinan; thyroid stimulating hormone; tin ethyl etiopurpurin; tirapazamine; titanocene bichloride; topsentin; toremifene; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; trimetrexate; triptorelin; tropisetron; turosteride; tyrosine kinase inhibitors; tyrphostins; UBC inhibitors; ubenimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonists; vapreotide; variolin B; vector system, erythrocyte gene therapy; velaresol; veramine; verdins; verteporfin; vinorelbine; vinxaltine; vitaxin; vorozole; zanoterone; zeniplatin; zilascorb; and zinostatin stimalamer.


Examples of useful therapeutic agents for treating or preventing UI include, but are not limited to, propantheline, imipramine, hyoscyamine, oxybutynin, and dicyclomine.


Examples of useful therapeutic agents for treating or preventing an ulcer include, antacids such as aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, and calcium bicarbonate; sucraflate; bismuth compounds such as bismuth subsalicylate and bismuth subcitrate; H2 antagonists such as cimetidine, ranitidine, famotidine, and nizatidine; H+, K+-ATPase inhibitors such as omeprazole, iansoprazole, and lansoprazole; carbenoxolone; misprostol; and antibiotics such as tetracycline, metronidazole, timidazole, clarithromycin, and amoxicillin.


Examples of useful therapeutic agents for treating or preventing IBD include, but are not limited to, anticholinergic drugs; diphenoxylate; loperamide; deodorized opium tincture; codeine; broad-spectrum antibiotics such as metronidazole; sulfasalazine; olsalazine; mesalamine; prednisone; azathioprine; mercaptopurine; and methotrexate.


Examples of useful therapeutic agents for treating or preventing IBS include, but are not limited to, propantheline; muscarine receptor antogonists such as pirenzapine, methoctramine, ipratropium, tiotropium, scopolamine, methscopolamine, homatropine, homatropine methylbromide, and methantheline; and antidiarrheal drugs such as diphenoxylate and loperamide.


Examples of useful therapeutic agents for treating or preventing an addictive disorder include, but are not limited to, methadone, desipramine, amantadine, fluoxetine, buprenorphine, an opiate agonist, 3-phenoxypyridine, levomethadyl acetate hydrochloride, and serotonin antagonists.


Examples of useful therapeutic agents for treating or preventing Parkinson's disease and parkinsonism include, but are not limited to, carbidopa/levodopa, pergolide, bromocriptine, ropinirole, pramipexole, entacapone, tolcapone, selegiline, amantadine, and trihexyphenidyl hydrochloride.


Examples of useful therapeutic agents for treating or preventing anxiety include, but are not limited to, benzodiazepines, such as alprazolam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, demoxepam, diazepam, estazolam, flumazenil, flurazepam, halazepam, lorazepam, midazolam, nitrazepam, nordazepam, oxazepam, prazepam, quazepam, temazepam, and triazolam; non-benzodiazepine agents, such as buspirone, gepirone, ipsapirone, tiospirone, zolpicone, zolpidem, and zaleplon; tranquilizers, such as barbituates, e.g., amobarbital, aprobarbital, butabarbital, butalbital, mephobarbital, methohexital, pentobarbital, phenobarbital, secobarbital, and thiopental; and propanediol carbamates, such as meprobamate and tybamate.


Examples of useful therapeutic agents for treating or preventing epilepsy include, but are not limited to, carbamazepine, ethosuximide, gabapentin, lamotrigine, phenobarbital, phenyloin, primidone, valproic acid, trimethadione, benzodiazepines, γ-vinyl GABA, acetazolamide, and felbamate.


Examples of useful therapeutic agents for treating or preventing stroke include, but are not limited to, anticoagulants such as heparin, agents that break up clots such as streptokinase or tissue plasminogen activator, agents that reduce swelling such as mannitol or corticosteroids, and acetylsalicylic acid.


Examples of useful therapeutic agents for treating or preventing a seizure include, but are not limited to, carbamazepine, ethosuximide, gabapentin, lamotrigine, phenobarbital, phenyloin, primidone, valproic acid, trimethadione, benzodiazepines, gabapentin, lamotrigine, γ-vinyl GABA, acetazolamide, and felbamate.


Examples of useful therapeutic agents for treating or preventing a pruritic condition include, but are not limited to, naltrexone; nalmefene; danazol; tricyclics such as amitriptyline, imipramine, and doxepin; antidepressants such as those given below, menthol; camphor; phenol; pramoxine; capsaicin; tar; steroids; and antihistamines.


Examples of useful therapeutic agents for treating or preventing psychosis include, but are not limited to, phenothiazines such as chlorpromazine hydrochloride, mesoridazine besylate, and thoridazine hydrochloride; thioxanthenes such as chloroprothixene and thiothixene hydrochloride; clozapine; risperidone; olanzapine; quetiapine; quetiapine fumarate; haloperidol; haloperidol decanoate; loxapine succinate; molindone hydrochloride; pimozide; and ziprasidone.


Examples of useful therapeutic agents for treating or preventing Huntington's chorea include, but are not limited to, haloperidol and pimozide.


Examples of useful therapeutic agents for treating or preventing ALS include, but are not limited to, baclofen, neurotrophic factors, riluzole, tizanidine, benzodiazepines such as clonazepan and dantrolene.


Examples of useful therapeutic agents for treating or preventing cognitive disorders include, but are not limited to, agents for treating or preventing dementia such as tacrine; donepezil; ibuprofen; antipsychotic drugs such as thioridazine and haloperidol; and antidepressant drugs such as those given below.


Examples of useful therapeutic agents for treating or preventing a migraine include, but are not limited to, sumatriptan; methysergide; ergotamine; caffeine; and beta-blockers such as propranolol, verapamil, and divalproex.


Examples of useful therapeutic agents for treating or preventing vomiting include, but are not limited to, 5-HT3 receptor antagonists such as odansteron, dolasetron, granisetron, and tropisetron; dopamine receptor antagonists such as prochlorperazine, thiethylperazine, chlorpromazin, metoclopramide, and domperidone; glucocorticoids such as dexamethasone; and benzodiazepines such as lorazepam and alprazolam.


Examples of useful therapeutic agents for treating or preventing dyskinesia include, but are not limited to, reserpine and tetrabenazine.


Examples of useful therapeutic agents for treating or preventing depression include, but are not limited to, tricyclic antidepressants such as amitryptyline, amoxapine, bupropion, clomipramine, desipramine, doxepin, imipramine, maprotiline, nefazadone, nortriptyline, protriptyline, trazodone, trimipramine, and venlafaxine; selective serotonin reuptake inhibitors such as citalopram, (S)-citalopram, fluoxetine, fluvoxamine, paroxetine, and setraline; monoamine oxidase inhibitors such as isocarboxazid, pargyline, phenelzine, and tranylcypromine; and psychostimulants such as dextroamphetamine and methylphenidate.


A Cyclo(hetero)alkenyl Compound and the other therapeutic agent can act additively or in one embodiment, synergistically. In one embodiment, a Cyclo(hetero)alkenyl Compound is administered concurrently with another therapeutic agent, for example, a composition comprising an effective amount of a Cyclo(hetero)alkenyl Compound, an effective amount of another therapeutic agent can be administered. Alternatively, a composition comprising an effective amount of a Cyclo(hetero)alkenyl Compound and a different composition comprising an effective amount of another therapeutic agent can be concurrently administered. In another embodiment, an effective amount of a Cyclo(hetero)alkenyl Compound is administered prior or subsequent to administration of an effective amount of another therapeutic agent. In this embodiment, the Cyclo(hetero)alkenyl Compound is administered while the other therapeutic agent exerts its therapeutic effect, or the other therapeutic agent is administered while the Cyclo(hetero)alkenyl Compound exerts its preventative or therapeutic effect for treating or a Condition.


A composition of the invention is prepared by a method comprising admixing a Cyclo(hetero)alkenyl Compound or pharmaceutically acceptable salt and a pharmaceutically acceptable carrier or excipient. Admixing can be accomplished using methods well known for admixing a compound (or salt) and a pharmaceutically acceptable carrier or excipient. In one embodiment the composition is prepared such that the Cyclo(hetero)alkenyl Compound is present in the composition in an effective amount.


4.6 Kits

The invention encompasses kits that can simplify the administration of a Cyclo(hetero)alkenyl Compound to an animal.


A typical kit of the invention comprises a unit dosage form of a Cyclo(hetero)alkenyl Compound. In one embodiment, the unit dosage form is a container, which can be sterile, containing an effective amount of a Cyclo(hetero)alkenyl Compound and a pharmaceutically acceptable carrier or excipient. The kit can further comprise a label or printed instructions instructing the use of the Cyclo(hetero)alkenyl Compound to treat or prevent a Condition. The kit can also further comprise a unit dosage form of another therapeutic agent, for example, a second container containing an effective amount of the other therapeutic agent and a pharmaceutically acceptable carrier or excipient. In another embodiment, the kit comprises a container containing an effective amount of a Cyclo(hetero)alkenyl Compound, an effective amount of another therapeutic agent and a pharmaceutically acceptable carrier or excipient. Examples of other therapeutic agents include, but are not limited to, those listed above.


Kits of the invention can further comprise a device that is useful for administering the unit dosage forms. Examples of such a device include, but are not limited to, a syringe, a drip bag, a patch, an inhaler, and an enema bag.


The following examples are set forth to assist in understanding the invention and should not be construed as specifically limiting the invention described and claimed herein. Such variations of the invention, including the substitution of all equivalents now known or later developed, which would be within the purview of those skilled in the art, and changes in formulation or minor changes in experimental design, are to be considered to fall within the scope of the invention incorporated herein.


5. EXAMPLES
5.1 Example 1
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A26(a)



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About 1 eq. of 2,3-dichloropyridine A and 1 eq. of a Compound of Formula B were heated in DMSO (1 ml/mmol) in the presence of about 1 eq. of DIEA at a temperature of about 125° C. for about 12 h. The resulting reaction mixture was cooled to about 25° C. and the solvent was removed under reduced pressure to provide a Compound of Formula C.


The Compound of Formula C was then reacted with 30% TFA in DCM (5 mL/mmol) at a temperature of from about 25° C. to about the boiling point of the solvent. The resulting reaction mixture was cooled to about 25° C., neutralized with aq. Na2CO3, and the organic layer separated from the aqueous layer. The aqueous layer was then extracted with DCM, the organic layers combined and dried (MgSO4), and the solvent removed under reduced pressure to provide a Compound of Formula D. The Compound of Formula D was purified using a silica gel column eluted with 15:1 hexane-ethyl acetate.


The Compound of Formula D (1 eq.) was reacted with 1.25 eq. of LiHMDS at about −78° C. and the resulting reaction mixture allowed to stir at about −78° C. for about 2 h. After stirring for about 2 h, 3 eq. of N-(5-chloro-2-pyridyl)triflimide 5 was added to the reaction mixture at a temperature of about −78° C. The reaction mixture was then stirred for about 2.5 h at a temperature of about −78° C. and then allowed to warm to about 25° C. The solvent was removed under reduced pressure and the resulting residue purified using a silica gel column eluted with 20:1 hexane-ethyl acetate provide a Compound of Formula E.


The Compound of Formula E (about 1 eq.), 4-(tert-butyl)aniline (about 2 eq.), and triethylamine (about 2.2 eq.) were dissolved in DMF (about 1 mL/mmol) and the resulting solution was degassed by bubbling N2 through the solution. Pd(OAc)2 and Dppp (about 0.3 eq. of each) were added to the solution and the nitrogen atmosphere was replaced with CO at a pressure of about 1 atm. The reaction mixture was then heated to about 70° C. for about 2 h. The reaction mixture was cooled to about 25° C. and the solvent removed under reduced pressure to provide a residue. The resulting residue was purified using silica gel column chromatography eluted with 5:1 hexane-ethyl acetate to provide Cyclo(hetero)alkenyl Compound A26(a).


The structure of Cyclo(hetero)alkenyl Compound A26(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry (LCMS).


Compound of Formula A26(a): 1H-NMR (CDCl3): 1.33 (s, 9H), 2.71 (m, 2H), 3.60 (t, 2H, J=5.73 Hz), 4.12 (m, 2H), 6.80 (m, 1H), 6.88 (dd, 1H, J=4.9, 7.6 Hz), 7.38 (m, 2H), 7.42 (m, 1H), 7.5 (m, 2H), 7.64 (dd, 1H, J=1.84, 2.02 Hz), 8.21 (dd, 1H, J=1.83, 4.88 Hz); LCMS: 370 (M+1).


5.2 Example 2
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A98(a)

Cyclo(hetero)alkenyl Compound A98(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound A26(a) as described in Example 1 except that 2-chloro-3-(trifluoromethyl)pyridine was used in place of 2,3-dichloropyridine.


The structure of Cyclo(hetero)alkenyl Compound A98(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry.


Compound of Formula A98(a): 1H NMR (400 MHz, CDCl3): δ ppm: 1.31 (s, 9H), 2.66 (m, 2H), 3.51 (t, 2H), 4.05 (dd, 2H), 6.75 (m, 1H), 6.97 (dd, 1H), 7.36 (d, 2H), 7.47 (t, 3H), 7.87 (dd, 1H), 8.41 (dd, 1H); LCMS (M+1): 404.2.


5.3 Example 3
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A34(a)

Cyclo(hetero)alkenyl Compound A34(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound A26(a) as described in Example 1 except that 4-(trifluoromethyl)aniline was used in place of 4-(tert-butyl)aniline.


The structure of Cyclo(hetero)alkenyl Compound A34(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry.


Compound of Formula A34(a): 1H NMR (400 MHz, CDCl3) 2.72 (m, 2H), 3.60 (t, 2H, J=5.47 Hz), 4.14 (m, 2H), 6.85 (m, 1H), 6.89 (dd, 1H, J—=4.58, 7.69 Hz), 7.62 (d, 2H, J=8.8 Hz), 7.66 (m, 2H), 7.72 (d, 2H, J=8.3 Hz), 8.21 (m, 1H); LCMS: 382 (M+1).


5.4 Example 4
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A29(a)

Cyclo(hetero)alkenyl Compound A29(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound A26(a) as described in Example 1 except that 4-(iso-propyl)aniline was used in place of 4-(tert-butyl)aniline.


Cyclo(hetero)alkenyl Compound A29(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry.


Compound of Formula A29(a): 1H NMR (400 MHz, CD3OD): δ ppm: 1.21 (bs, 6H), 2.61 (bs, 2H), 2.75 (bm, 1H), 3.55 (bs, 2H), 4.12 (bs, 2H), 6.70 (s, 1H), 6.82 (m, 1H), 7.21 (t, 2H), 7.40 (s, 1H), 7.45 (t, 2H), 7.77 (t, 1H), 8.25 (s, 1H); LCMS: 382 (M+1).


5.5 Example 5
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A75(a)

Cyclo(hetero)alkenyl Compound A75(a) was obtained by a method analogous to that used to obtain the Cyclo(hetero)alkenyl Compound A26(a) as described in Example 1 except that 2-chloro-3-methylpyridine was used in place of 2,3-dichloropyridine and the Compound of Formula C was obtained by the following method: 2-chloro-3-methyl pyridine (about 1 eq.), a Compound of Formula B (about 1.2 eq.), and sodium tert-butoxide (1.5 eq.) were dissolved in glyme (0.66 mL/mmol), and the resulting solution was degassed by bubbling N2 through the solution.


After the solution was degassed, 0.02 eq. of tris-(dibenzylideneacetone)dipalladium (0) catalyst and 0.02 eq. of the ligand depicted below




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were added to the solution and the resulting reaction mixture was heated at a temperature of about 50° C. for about 4.5 h. The reaction mixture was cooled to about 25° C. and solids removed by filtering over CELITE. The solvent was then removed under reduced pressure to provide a residue. The resulting residue was purified by column chromatography using a silica gel column eluted with 6:1 hexane-ethyl acetate to provide the Cyclo(hetero)alkenyl Compound A75(a).


The structure of Cyclo(hetero)alkenyl Compound A75(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry.


Compound of Formula A75(a): 1H NMR (400 MHz, CDCl3): 1.33 (s, 9H), 2.33 (s, 3H), 2.67 (m, 2H), 3.33 (t, 2H), 3.99 (m, 2H), 6.81 (m, 1H), 6.89 (m, 1H), 7.38 (m, 2H), 7.46 (m, 2H), 7.50 (m, 2H), 8.19 (m, 1H); LCMS: 350 (M+1).


5.6 Example 6
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A81(a)

Cyclo(hetero)alkenyl Compound A81(a) was obtained by a method analogous to that used to obtain the Cyclo(hetero)alkenyl Compound A75(a) as described in Example except that 4-(isopropoxy)aniline was used in place of 4-(tert-butyl)aniline.


The structure of Cyclo(hetero)alkenyl Compound A81(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry.


Compound of Formula A81(a): 1H NMR (400 MHz, CD3OD): 1.32 (d, 6H, J=5.98 Hz), 2.35 (s, 3H), 2.62 (m, 2H), 3.32 (m, 2H), 3.92 (m, 2H), 4.58 (m, 2H), 6.80 (m, 1H), 6.89 (m, 2H), 6.97 (m, 1H), 7.48 (m, 2H), 7.58 (m, 1H), 8.1 (m, 1H); LCMS: 351 (M+).


5.7 Example 7
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A77(a)

Cyclo(hetero)alkenyl Compound A77(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound A75(a) as described in Example 5 except that 4-(iso-propyl)aniline was used in place of 4-(tert-butyl)aniline.


The structure of Cyclo(hetero)alkenyl Compound A77(a) was confirmed by 1H NMR and mass spectrometry (MS).


Compound of Formula A77(a): 1H NMR (400 MHz, CD3OD): δ ppm: 1.25 (bd, 6H), 2.22 (s, 3H), 2.61 (bs, 2H), 2.75 (m, 1H), 3.27 (m, 2H), 3.92 (s, 2H), 6.71 (s, 1H), 6.85 (m, 1H), 7.23 (t, 2H), 7.52 (bm, 4H), 8.15 (s, 1H); MS (EI): m/z 335 (M+1).


5.8 Example 8
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A82(a)

Cyclo(hetero)alkenyl Compound A82(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound A75(a) as described in Example 5 except that (4-trifluoromethyl)aniline was used in place of 4-(tert-butyl)aniline.


The structure of Cyclo(hetero)alkenyl Compound A82(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry.


Compound of Formula A82(a): 1H NMR (400 MHz, CDCl3): 2.33 (s, 3H), 2.67 (m, 2H), 3.34 (t, 2H, J=5.48 Hz), 4.01 (dd, 2H, J=2.88, 6.16 Hz), 6.86 (m, 1H), 6.91 (dd, 1H, J=5.09, 7.5 Hz), 7.46 (m, 1H), 7.62 (d, 2H, J=8.47), 7.65 (b, 1H), 7.73 (d, 2H, J=8.5 Hz), 8.18 (m, 1H); LCMS: 362 (M+1).


5.9 Example 9
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A170(a)



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A Compound of Formula F (about 1 eq.), a Compound of Formula 2 (about 1 eq.) (commercially available from Sigma-Aldrich, St. Louis, Mo. (www.sigma-aldrich.com)), and triethylamine (about 2.2 eq.) were dissolved in DMF (5 mL/mmol) and the resulting solution was stirred at about 25° C. for about 5 h. The solvent was then removed under reduced pressure to provide a yellow residue. The residue was dissolved in methylene chloride and filtered through CELITE. The solvent was then removed from the resulting filtrate under reduced pressure to provide a Compound of Formula H which was used without further purification. The Compound of Formula H (about 1 eq.), 4-tert-butyl aniline (about 5 eq.), 1-hydroxybenzotriazole (HOBt, about 1 eq.), and DIC (about 1 eq.) were dissolved in DCM and the resulting solution was stirred at about 25° C. for about 2 days. The solvent was removed under reduced pressure and the resulting residue was purified using silica gel column chromatography eluted with 10:1 hexane-ethyl acetate to provide Cyclo(hetero)alkenyl Compound A170(a) as a yellow solid.


The structure of Cyclo(hetero)alkenyl Compound A170(a) was confirmed by 1H NMR and mass spectrometry.


Compound of Formula A170(a): 1H NMR (400 MHz, CD3OD): δ ppm: 1.25 (bd, 6H), 2.22 (s, 3H), 2.61 (bs, 2H), 2.75 (m, 1H), 3.27 (m, 2H), 3.92 (s, 2H), 6.71 (s, 1H), 6.85 (m, 1H), 7.23 (t, 2H), 7.52 (bm, 4H), 8.15 (s, 1H); MS (EI): m/z 335 (M+1).


5.10 Example 10
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula B38(a)

Cyclo(hetero)alkenyl Compound B38(a) was obtained by a method analogous to that used to obtain the Cyclo(hetero)alkenyl Compound A26(a) as described in Example 1 except that 0.2 eq. of 2-amino-6-methylbenzothiazole was used in place of 0.3 eq. 4-(tert-butyl)aniline.


The structure of Cyclo(hetero)alkenyl Compound B38(a) was confirmed by 1H NMR and liquid chromatography-mass spectrometry.


Compound of Formula B38(a): 1H NMR (400 MHz, CDCl3): δ ppm: 11.25 (s, 1H), 8.15 (dd, 1H), 7.62 (m, 3H), 7.12 (dd, 1H), 6.87 (dd, 1H), 6.81 (m, 1H), 3.83 (m, 2H), 3.57 (t, 2H), 2.78 (m, 2H), 2.40 (s, 3H); LCMS (M+H+): 385.


5.11 Example 11
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula B37(a)

Cyclo(hetero)alkenyl Compound B37(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound B38(a) as described in Example 10 except that 2-amino-6-fluorobenzothiazole was used in place of 2-amino-6-methylbenzothiazole.


The structure of Cyclo(hetero)alkenyl Compound B37(a) was confirmed by 1H NMR and mass spectrometry.


Compound of Formula B37(a): 1H NMR (400 MHz, DMSO): δ ppm: 2.61 (s, 2H), 3.50 (s, 2H), 4.05 (s, 2H), 7.10 (m, 1H), 7.20 (s, 1H), 7.35 (m, 1H), 7.75 (m, 1H), 7.80 (t, 1H), 7.92 (m, 1H), 8.23 (s, 1H), 12.20 (s, 1H); MS (EI): m/z 389 (M+1).


5.12 Example 12
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula B85(a) AND B84(a)

Cyclo(hetero)alkenyl Compound B85(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound B38(a) as described in Example 10 except that 2-chloro-3-(trifluoromethyl)pyridine was used in place 2,3-dichloropyridine.


Cyclo(hetero)alkenyl Compound B84(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound B38(a) as described in Example 10 except that 2-chloro-3-(trifluoromethyl)pyridine was used in place 2,3-dichloropyridine, and 2-amino-6-fluorobenzothiazole was used in place of 2-amino-6-methylbenzothiazole.


The structure of Cyclo(hetero)alkenyl Compound B85(a) was confirmed by 1H NMR and mass spectrometry.


Compound of Formula B85(a): 1H NMR (CDCl3): 2.46 (s, 3H), 2.74 (m, 2H), 3.54 (t, 2H, J=5.49 Hz), 4.00 (dd, 2H, J=2.86, 6.16 Hz), 6.92 (m, 1H), 7.02 (dd, 1H, J=4.16, 8.36 Hz), 7.20 (m, 1H), 7.63 (m, 2H), 7.91 (dd, 1H, J=2, 7.96 Hz), 8.44 (m, 1H), 9.90 (b, 1H); MS: 419 (M+1).


The structure of Cyclo(hetero)alkenyl Compound B84(a) was confirmed by 1H NMR and mass spectrometry.


Compound of Formula B84(a): 1H NMR (400 MHz, CDCl3): δ ppm: 2.73 (m, 2H), 3.52 (t, 2H), 3.95 (d, 2H), 6.90 (s, 1H), 7.06 (m, 2H), 7.51 (dd, 1H), 7.65 (dd, 1H), 7.91 (d, 1H), 8.41 (dd, 1H), 10.27 (broad s, 1H); MS: 423.1 (M+1).


5.13 Example 13
Synthesis of a Cyclo(Hetero)Alkenyl Compounds of FORMULA B62(a) AND B63(a)

Cyclo(hetero)alkenyl Compound B62(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound A75(a) as described in Example 5 except that 2-amino-6-fluorobenzothiazole was used in place 4-(tert-butyl)aniline.


Cyclo(hetero)alkenyl Compound B63(a) was obtained by a method analogous to that used to obtain the Cyclo(hetero)alkenyl Compound A75(a) as described in Example except that 2-amino-6-methylbenzothiazole was used in place 4-(tert-butyl)aniline.


The structure of Cyclo(hetero)alkenyl Compound B62(a) was confirmed by 1H NMR and mass spectrometry.


Compound of Formula B62(a): 1H NMR (CDCl3): 9.82 (br, 1H), 8.17 (dd, 1H, J=1.9 and 4.8 Hz), 7.71 (dd, 1H, J=4.8 and 8.7 Hz), 7.54 (dd, 1H, J=2.6 and 8.1 Hz), 7.46 (d, 1H, J=7.2 Hz), 7.15 (ddd, 1H, J=2.3, 6.4 and 8.7 Hz), 7.0-7.04 (m, 1H), 6.91 (dd, 1H, J=4.8 and 7.4 Hz), 3.95 (dd, 2H, J=2.8 and 6.4 Hz), 3.35 (dd, 2H, J=5.4 and 5.8 Hz), 2.68-2.74 (m, 2H), 2.31 (s, 3H); MS: 369 (M+1).


The structure of Cyclo(hetero)alkenyl Compound B63(a) was confirmed by 1H NMR and mass spectrometry.


Compound of Formula B63(a): 1H NMR (CDCl3): 9.80 (br, 1H), 8.19 (dd, 1H, J=1.3 and 4.8 Hz), 7.64-7.66 (m, 2H), 7.45 (d, 1H, J=7.2 Hz), 7.23 (dd, 1H, J=1.9 and 8.3 Hz), 6.99-7.0 (m, 1H), 6.85 (dd, 1H, J—=4.8 and 7.2 Hz), 3.92-3.95 (m, 2H), 3.34 (dd, 2H, 5.4 and 5.5 Hz), 2.68-2.72 (m, 2H), 2.48 (s, 3H), 2.31 (s, 3H); MS: 365 (M+1).


5.14 Example 14
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula K1(a)

Cyclo(hetero)alkenyl Compound K1(a) was obtained by a method analogous to that used to obtain Cyclo(hetero)alkenyl Compound A26(a) as described in Example 1 except that 2,2-difluoro-5-aminobenzodioxole (commercially available from Lancaster Synthesis of Windam, N.H.) was used in place of tert-butyl aniline.


The structure of Cyclo(hetero)alkenyl Compound K1(a) was confirmed by 1H NMR.


Compound of Formula K1(a): 1H NMR (400 MHz, CDCl3): δ ppm: 8.20-8.17 (m 1H), 6.68-7.65 (m, 1H), 7.64-7.61 (m, 1H), 7.43 (bs, 1H), 7.02-6.99 (m, 2H), 6.89-6.85 (m, 1H), 6.83-6.78 (m, 1H), 4.14-4.08 (m, 2H), 3.61-3.55 (m, 2H), 2.72-2.65 (m, 2H).


5.15 Example 15
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A34(a)



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A Compound of Formula C was obtained, in one method, by a method analogous to that described in Example 1 except that the heating was at a temperature of about 140° C. for about 12 hours.


A Compound of Formula C was obtained, in another method, by adding at a temperature of about 25° C. the Compound of Formula A (51.9 g, 350 mmol) to a suspension of the Compound of Formula B (50.3 g. 350 mmol) and K2CO3 (120 g, 875 mmol) in DMSO to form a reaction mixture. The reaction mixture was stirred at 150° C. for about 16 hours. Thereafter, the reaction mixture was cooled to about 25° C. and quenched with water. The resulting liquid was extracted 3 times with EtOAc (300 mL per extraction), the organic layers combined and dried (Na2SO4), and the solvent removed to provide the Compound of Formula C (92.5% yield) with a purity of >90%, as determined by LCMS.


The Compound of Formula C (about 0.25 mmol/mL) was reacted with 4N HCl in THF at a temperature of about 50° C. for about 16 hours. The resulting reaction mixture was cooled to about 25° C. and neutralized with aqueous Na2CO3. Separate aqueous and organic layers formed. The organic layer was separated from the aqueous layer. The aqueous layer was then extracted with about 150-300 mL of ethyl acetate. The organic layer was combined with the post-extraction ethyl acetate and the combination was dried with MgSO4. The solvent was removed under reduced pressure to provide a Compound of Formula D. The Compound of Formula D was purified using a silica gel column eluted with 3:1 hexane:ethyl acetate (80% yield).


The Compound of Formula D (1 eq., about 0.3 mmol/mL) was reacted with 1.2 eq. of aqueous NaCN within the temperature range of from 0° C. to 25° C. for about 12 hours. The solvent was removed under reduced pressure and the resulting residue was purified using a silica gel column eluted with 3:1 hexane:ethyl acetate provide a Compound of Formula J (99% yield).


The Compound of Formula J (about 1 eq., about 0.25 mmol/mL) was reacted with 2.2 eq. of POCl3 in pyridine at a temperature of about 25° C. for about 22 hours. The solvent was removed under reduced pressure and the resulting residue was purified using a silica gel column eluted with 5:1 hexane:ethyl acetate provide a Compound of Formula K (91% yield).


The Compound of Formula K (about 0.5 mmol/mL) was refluxed in 6N aqueous HCl at a temperature of about 100° C. for about 12 hours. The resulting reaction mixture was cooled to about 25° C. and the solvent was removed under reduced pressure to provide a Compound of Formula L which was used without further purification (92% yield).


In a single step procedure, the Compound of Formula L (about 1 eq.), 4-trifluoromethyl-aniline (about 1 eq., obtained from Aldrich Chemical Co., Milwaukee, Wis.), 1-hydroxybenzotriazole (HOBt, about 1.25 eq.), and DIC (about 1.25 eq.) were dissolved in DMF (about 0.35 mmol/mL) and the resulting solution was stirred at a temperature of about 25° C. for about 12 hours. The solvent was removed under reduced pressure and the resulting residue was purified using silica gel column chromatography eluted with 10:1 hexane:ethyl acetate to provide 0.37 equivalents of Cyclo(hetero)alkenyl Compound A34(a) (37% yield).


In a two-step procedure, the Compound of Formula L (about 1 eq., about 0.6 mmol/mL) was reacted with excess SOCl2 (about 24 eq.) at a temperature of about 25° C. for about 12 hours in a first step to provide a Compound of Formula M, which was used without further purification. Then, in a second step, about 1 equivalent of the Compound of Formula M (about 1 mmol/5.0 mL), 4-trifluoromethyl-aniline (about 1.5 eq.), and triethylamine (about 2.0 eq.) were dissolved in DCM and the resulting solution was degassed by bubbling nitrogen through the solution. The reaction mixture was kept at about 25° C. for about 4 hours. The solvent was removed under reduced pressure to provide a residue. The resulting residue was purified using a silica gel column and eluted with 10:1 hexane:ethyl acetate to provide 0.63 equivalents of Cyclo(hetero)alkenyl Compound A34(a) (63% yield for the two-step procedure).


The structure of Cyclo(hetero)alkenyl Compound A34(a) was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula A34(a): 1H-NMR (CDCl3): 8.19 (dd, 1H, J=1.6, 7.7 Hz), 7.73 (d, 2H, J=10.1 Hz), 7.67-7.59 (m, 4H), 6.87 (dd, 1H, J=4.8, 7.7 Hz), 6.82 (m, 1H), 4.12 (dd, 2H, J=2.9, 6.3 Hz), 3.58 (t, 2H, J=5.5 Hz), 2.70 (m, 2H); MS: 382.1 (M+1).


5.16 Example 16
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A178(a)



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Isonicotinic acid N (15 g, 121.8 mmol, obtained from Aldrich Chemical Co.) was added to about 100 mL of thionyl chloride and the reaction mixture was stirred for about 17 h at about 25° C. After this period, excess SOCl2 was removed under reduced pressure to provide a white solid. About 400 mL of THF was added to the resulting solid and the solvent was removed under reduced pressure to provide isonicotinic acid chloride as a white powder. The white powder was dissolved in about 400 mL of THF. The solution was cooled to about 0° C. and 4-trifluoromethyl-aniline (21.6 g, 134.0 mmol, 1.1 eq., obtained from Aldrich Chemical Co.) and sodium bicarbonate (30 g, 365.4 mmol, 3.0 eq.) were added. The reaction mixture was stirred for about 5 min at about 0° C., warmed to about 25° C. over about 30 min, then heated to about 65° C. and kept at that temperature for about 1 h. After this period, the reaction mixture was cooled to about 25° C. and the THF was removed under reduced pressure. The residue was suspended in about 800 mL of ethyl acetate and washed with about 600 mL of aqueous 3N HCl. Separate aqueous and organic layers formed. The layers were separated and the aqueous layer was extracted three times with about 600 mL of ethyl acetate per extraction. The organic layer was combined with the post-extraction ethyl acetate aliquots. The combination was dried with Na2SO4 and the solvent was removed under reduced pressure to provide 32 g of the Compound of Formula O as a white solid (99% yield).


The structure of the Compound of Formula O was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula O: 1H-NMR (CD3OD) δ: 9.14-9.08 (m, 2H), 8.60-8.53 (m, 2H), 8.06-7.98 (m, 2H), 7.77-7.69 (m, 2H); MS: m/z=267.1.


The Compound of Formula O (31 g, 118.1 mmol) was suspended in a mixture of THF (400 mL) and DMF (100 mL) at about 25° C. and benzyl bromide (30.3 g, 177.1 mmol, obtained from Aldrich Chemical Co.) was added. The resulting reaction mixture was refluxed for about 24 hours at a temperature of about 80° C. After this period, the reaction mixture was cooled to about 25° C. and the resulting solid was filtered off. A majority of the THF was removed from the filtrate under reduced pressure. A precipitate formed when about 400 mL of diethyl ether was added to the DMF-enriched solution. The resulting solid was filtered off. The solids were combined and dried to provide 51 g of the Compound of Formula P (99% yield).


The structure of the Compound of Formula P was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula P: 1H-NMR (CD3OD) δ: 9.29-9.23 (m, 2H), 8.58-8.51 (m, 2H), 7.98-7.92 (m, 2H), 7.72-7.65 (m, 2H), 7.56-7.51 (m, 2H), 7.49-7.43 (m, 2H), 5.91 (s, 2H); MS: m/z=357.1.


The Compound of Formula P (48 g, 109.8 mmol) was suspended in about 600 mL of methanol, cooled to about 0° C., and sodium borohydride (13.3 g, 351.2 mmol) was added in several portions of about 1 g each over a period of about 30 min. The reaction mixture was stirred for about 1 h at about 0° C. and warmed to about 25° C. over about a 2 hour period. After this period, the methanol was removed under reduced pressure. The residue was diluted with about 800 mL of brine and about 1.5 L of ethyl acetate. Separate aqueous and organic layers formed. The layers were separated and the aqueous layer was washed twice with about 600 mL of ethyl acetate per wash. The organic layer was combined with the post-washing ethyl acetate aliquots. The combination was dried with Na2SO4 and the solvent was removed under reduced pressure to provide a brown residue. The residue was dissolved in about 200 mL of DCM. A precipitate formed when about 200 mL of hexane was added to the DCM solution. The resulting solid was filtered off. The solid was dried to provide 39 g of the Compound of Formula Q (98% yield).


The structure of the Compound of Formula Q was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula Q: 1H-NMR (CDCl3) δ: 7.70-7.64 (m, 2H), 7.62-7.56 (m, 4H), 7.48 (bs, 1H), 7.38-7.27 (m, 5H), 6.69-6.64 (m, 1H), 3.64 (s, 2H), 3.21-3.16 (m, 2H), 2.72-2.66 (m, 2H), 2.56-2.48 (m, 2H); MS: m/z=361.1.


Under a dry nitrogen atmosphere, α-chloroethylchloroformate (16 mL, 22.6 g, 158.1 mmol, obtained from Aldrich Chemical Co.) was added drop wise to a solution of the Compound of Formula Q (30 g, 83.2 mmol) in about 500 mL of DCE over a period of about 15 min at about 0° C. The reaction mixture was then warmed to about 25° C. over a period of about 30 min. The reaction mixture was then heated to about 83° C. and refluxed for about 4 hours at that temperature. After this period, the solvent and unreacted α-chloroethylchloroformate were removed under reduced pressure. The resulting residue was dissolved in about 500 mL of methanol. The methanol solution was refluxed for about 3 hours at a temperature of about 65° C. After this, the methanol was removed to provide 31.3 g of brown residue. The residue was dissolved in about 500 mL of DCM. A precipitate formed when about 300 mL of diethyl ether was added to the DCM solution. The resulting solid was filtered off. The solid was dried to provide 26 g of the Compound of Formula R as white solid. The 1H-NMR and LCMS analyses of the white solid showed that the sample was about 92-95% pure; therefore, the yield (based on the starting weight of compound Q used) was determined to be about 94-97%.


The structure of the Compound of Formula R was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula R: 1H-NMR (CD3OD) δ: 7.79-7.71 (m, 2H), 7.60-7.49 (m, 2H), 6.65-6.59 (m, 1H), 3.84-3.76 (m, 2H), 3.36-3.28 (m, 2H), 2.68-2.59 (m, 2H); LCMS: m/z=271.1.


The Compound of Formula R (10.5 g, 34.2 mmol), 2-chloro-3-nitropyridine (5.1 g, 32.2 mmol, obtained from Aldrich Chemical Co.) and triethylamine (19 mL, 13.8 g, 136.8 mmol) were mixed in about 500 mL of DCE at about 25° C. and kept for about 12 hours at about 25° C. After this period the mixture was poured into about 800 mL of aqueous sodium bicarbonate and about 800 mL of DCM. Separate aqueous and organic layers formed. The organic layer was separated from the aqueous layer. The organic layer was dried with Na2SO4 and the solvent was removed under reduced pressure to provide 14.2 g of crude product. The crude product was dissolved in about 300 mL of DCM. A precipitate formed when about 600 mL of hexane was added to the DCM solution. The resulting solid was filtered off and dried to provide 12.5 g of Cyclo(hetero)alkenyl Compound A178(a) as a yellow solid (99% yield).


The structure of Cyclo(hetero)alkenyl Compound A178(a) was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula A178(a): 1H-NMR (CDCl3) δ: 8.38-8.35 (m, 1H), 8.21-8.16 (m, 2H), 7.73-7.66 (m, 1H), 7.64-7.57 (m, 1H), 7.52 (bs, 1H), 6.84-6.79 (m, 1H), 6.75-6.71 (m, 1H), 4.06-4.01 (m, 2H), 3.76-3.70 (m, 2H), 2.74-2.67 (m, 2H); MS: m/z=393.1.


5.17 Example 17
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula AAA



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A mixture of zinc granules (13.9 g, 212.3 mmol) in ethanol (160 mL), water (40 mL), and HCl (10 mL) was cooled to about 0° C. A solution of Cyclo(hetero)alkenyl Compound A178(a) in about 120 mL of ethanol was added to the mixture. The resulting reaction mixture was stirred for about 1.5 h at about 0° C. After this period, the mixture was filtered and the solvent was removed from the filtrate under reduced pressure to provide a dark brown residue. The residue was dissolved in about 1 L of DCM and neutralized with 1N aqueous KOH to a pH of about 10. Separate aqueous and organic layers formed. The organic layer was separated from the aqueous layer. The organic layer was dried with Na2SO4 and the solvent was removed under reduced pressure to provide 9.2 g of a brown oil. The 1H-NMR and LCMS analyses of the oil showed that the sample was about 80-85% pure; therefore, the yield (based on the starting weight of Cyclo(hetero)alkenyl Compound AAA) of the Cyclo(hetero)alkenyl Compound AAA was determined to be about 96-100%.


The structure of Cyclo(hetero)alkenyl Compound AAA was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula AAA: 1H-NMR (CDCl3) δ: 7.82-7.79 (m, 1H), 7.73-7.68 (m, 2H), 7.63-7.57 (m, 3H), 7.01-6.96 (m, 1H), 6.91-6.83 (m, 2H), 3.95-3.89 (m, 2H), 3.83-3.75 (m, 2H), 3.35-3.29 (m, 2H), 2.68-2.60 (m, 2-1); LCMS: m/z 363.2.


5.18 Example 18
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A34(a)



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Cyclo(hetero)alkenyl Compound AAA (1.77 g, 4.88 mmol) was suspended in about 100 mL of 6N aqueous HCl, cooled to about 0° C., and treated with a solution of NaNO2 (0.34 g, 4.88 mmol) in about 40 mL of water with stirring. The resulting solution was stirred for about 30 minutes at about 0° C. Thereafter, a solution of (CuCl)2 (0.58 g, 5.86 mmol, obtained from Aldrich Chemical Co.) in about 50 mL of water was added. The resulting mixture was stirred for about 30 minutes at about 0° C., allowed to warm to about 25° C., then stirred for about 1 h at about 25° C. After this period, the mixture was diluted with about 300 mL of water and extracted twice with about 700 mL of ethyl acetate used per extraction. The post-extraction ethyl acetate aliquots were combined, dried with Na2SO4 and the solvent was removed to provide 1.8 g of a dark brown oil. This oil was purified by flash chromatography on a silica gel column, using a gradient of from 5:95 to 80:20 (by volume) ethyl acetate:hexane as an eluent, to provide 0.82 g of the Cyclo(hetero)alkenyl Compound A34(a) as tan solid (45% yield).


The structure of Cyclo(hetero)alkenyl Compound A34(a) was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula A34(a): 1H-NMR (CDCl3) δ: 8.19 (dd, 1H, J=1.54, 4.82 Hz), 7.73-7.67 (m, 2H), 7.65-7.56 (m, 4H), 6.87 (dd, 1H, J=4.6, 7.45 Hz), 6.85-6.82 (m, 1H), 4.14-4.09 (m, 2H), 3.58 (t, 2H, J=5.7 Hz), 2.74-2.66 (m, 2H); MS: m/z=382.1.


5.19 Example 19
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A36(a)

Compound A36(a) was prepared according to Example 1, except that 4-trifluoromethoxyphenyl amine was used in place of 4-(tert-butyl)aniline.


5.20 Example 20
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula L1(a)

Compound L1(a) was prepared according to Example 1, except that 4-chloro-3-trifluoromethylphenyl amine was used in place of 4-(tert-butyl)aniline.


5.21 Example 21
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A106(a)

Compound A106(a) was prepared according to Example 3, except that 2-chloro-3-trifluoropyridine was used in place of 2,3-dichloropyridine.


5.22 Example 22
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula L3(a)

Compound L3(a) was prepared according to Example 1, except that 4-methyl-3-trifluoromethylphenyl amine was used in place of 4-(tert-butyl)aniline.


5.23 Example 23
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula L4(a)

Compound L4(a) was prepared according to Example 1, except that 3-chloro-4-(trifluoromethylthio)benzenamine was used in place of 4-(tert-butyl)aniline.


5.24 Example 24
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula L5(a)

Compound L5(a) was prepared according to Example 1, except that 4-fluoro-3-trifluoromethylphenyl amine was used in place of 4-(tert-butyl)aniline.


5.25 Example 25
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula L7(a)

Compound L7(a) was prepared according to Example 1, except that 4-amino-2-trifluoromethylbenzonitrile was used in place of 4-(tert-butyl)aniline.


5.26 Example 26
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A44(a)

Compound A44(a) was prepared according to Example 1, except that 4-(1,1,2,2-tetrafluoroethoxy)benzenamine was used in place of 4-(tert-butyl)aniline.


5.27 Example 27
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A43(a)

Compound A43(a) was prepared according to Example 1, except that N,N-diethylbenzene-1,4-diamine was used in place of 4-(tert-butyl)aniline.


5.28 Example 28
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A34(b)

Compound A34(b) was prepared according to Example 1, except that 4-trifluoromethylphenyl amine was used in place of 4-(tert-butyl)aniline and 1-(3-chloropyridin-2-yl)-3-methylpiperidin-4-one, the reaction product of 3-methylpiperidin-4-one with 2,3-dichloropyridine (Compound of Formula A), was used in place of the Compound of Formula D.


3-Methylpiperidin-4-one was prepared by debenzylating 1-benzyl-3-methylpiperidin-4-one as follows. 70 g (344.3 mmol) of 1-benzyl-3-methylpiperidin-4-one (available from Across Organics, Piscataway, N.J.) was dissolved in methanol (400 mL) under a nitrogen atmosphere. 5.6 g of a Pd/C catalyst was added to form a reaction mixture. The nitrogen atmosphere was replaced by a hydrogen atmosphere. The reaction mixture was stirred at 25° C. for 48 hours and then filtered through a pad of CELITE (about 200 g). The filtrate was concentrated by removing the solvent under reduced pressure to provide 38 g of 3-methylpiperidin-4-one.


1-(3-Chlioropyridin-2-yl)-3-methylpiperidin-4-one was prepared by dissolving 19.2 g 3-methylpiperidin-4-one (168.9 mmol) and 25 g of Compound of Formula A (168.9 mmol) in DMSO (400 mL) under a nitrogen atmosphere to form a reaction mixture. The reaction mixture was stirred at 85° C. for 12 hours. Thereafter, the solvent was removed under reduced pressure. The residue was purified by column chromatography on a silica gel column, using a gradient of from 10:90 to 98:2 (by volume) ethyl acetate:hexane as an eluent, to provide 9 g of 1-(3-chloropyridin-2-yl)-3-methylpiperidin-4-one.


The structure of Cyclo(hetero)alkenyl Compound A34(b) was confirmed by 1H-NMR.


Compound of Formula A34(b): 1H NMR (400 MHz, CDCl3): δ ppm: 8.20 (dd, 1H, J=4.82, 1.53 Hz), 7.74-7.69 (m, 2H), 7.64-7.58 (m, 4H), 6.87 (dd, 1H, J=7.45, 4.82 Hz), 6.61 (bt, 1H, J=3.29 Hz), 4.17-4.09 (m, 1H), 3.99 (td, 1H, J=19.1, 2.85 Hz), 3.64 (dd, 1H, J=12.49, 3.94 Hz), 3.34 (dd, 1H, J=12.71, 4.38 Hz), 3.13-3.04 (m, 1H), 1.29 (d, 3H, J=6.79 Hz).


5.29 Example 29
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula K4(a)

Compound K4(a) was prepared according to Example 21, except that 2,2-difluoro-5-aminobenzodioxole was used in place of 4-(trifluoromethyl)aniline.


5.30 Example 30
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A42(a)

Compound A42(a) was prepared according to Example 1, except that 4-(trifluoromethylthio)benzenamine was used in place of 4-(tert-butyl)aniline.


5.31 Example 31
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula M1(a)

Compound M1(a) was prepared according to Example 1, except that 5-trifluoromethylpyridin-2-yl amine was used in place of 4-(tert-butyl)aniline.


5.32 Example 32
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula M23(a)

Compound M23(a) was prepared according to Example 1, except that 6-trifluoromethylpyridin-3-yl amine was used in place of 4-(tert-butyl)aniline.


5.33 Example 33
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula M4(a)

Compound M4(a) was prepared according to Example 31, except that 2-chloro-3-trifluoromethylpyridine was used in place of 2,3-dichloropyridine.


5.34 Example 34
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula M26(a)

Compound M26(a) was prepared according to Example 33, except that 6-trifluoromethylpyridin-3-yl amine was used in place of 5-trifluoromethylpyridin-2-yl amine.


5.35 Example 35
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula E34(a)

Compound E34(a) was prepared according to Example 3, except that 2,3-dichloropyrazine was used in place of 2,3-dichloropyridine.


5.36 Example 36
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A58(a)

Compound A58(a) was prepared according to Example 3, except that 2-chloro-3-fluoropyridine was used in place of 2,3-dichloropyridine.


5.37 Example 37
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula M2(a)



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1.1 eq. of the piperidinyl ketal 1,4-dioxa-8-azaspiro[4.5]-decane (B) was added to a 1.2M solution of 2-chloro-3-fluoropyridine (AAB, 1 eq.) in toluene (96 mL), followed by the addition of 1.1 eq. of the sodium salt of 2-methylpropan-2-ol (“NaOtBu”), 0.05 eq. Pd(OAc)2, and 0.05 eq. Dppp to form a reaction mixture. The atmosphere in contact with the reaction mixture was replaced by nitrogen. The reaction mixture was stirred with a magnetic stirring bar and heated to 65° C. The reaction mixture was stirred at this temperature for 3 h. The reaction mixture was then cooled to about 25° C. and filtered through about 200 g of CELITE powder that had been prewetted with about 200 mL of EtOAc. The solvent was partially removed under reduced pressure to provide a residue. The residue was purified by passing through a silica gel pad with a solution of 50% EtOAc in hexane by volume. This provided the Compound of Formula AAC as a yellow oil (94% yield) which was shown, by LC/MS, to be about 99% pure. The structure of the Compound of Formula AAC was confirmed by 1H-NMR spectrometry.


Compound of Formula AAC: 1H-NMR (CDCl3) δ: 8.01-7.97 (m, 1H), 7.25-7.17 (m, 1H), 6.75-6.69 (m, 1H), 4.02 (s, 4H), 3.64-3.57 (m, 4H), 1.86-1.80 (m, 4H).


The Compound of Formula AAC, prepared as described above, was used without further purification. 1 eq. of the Compound of Formula AAC was dissolved in 60 mL THF. Thereafter, an equal volume of 4N aqueous HCl was added to form a reaction mixture. The reaction mixture was stirred while heating to 60° C. and stirred at this temperature for 3 h. The reaction mixture was then to cooled to about 25° C. The solution was made basic by adding aqueous K2CO3, extracted with EtOAc, dried over Na2SO4, and the solvent was removed under reduced pressure to provide a residue. The residue was purified by chromatography on a silica gel column, using a gradient of from 0:100 to 5:95 (by volume) methanol:(10% diethyl ether in hexane by volume) as an eluent, to provide, after removing the solvent under reduced pressure, the ketone Compound of Formula AAD as a yellow oil (82% yield). The structure of the Compound of Formula AAD was confirmed by 1H-NMR spectrometry.


Compound of Formula AAD: 1H-NMR (CDCl3) δ: 8.06-8.01 (m, 1H), 7.33-7.25 (m, 1H), 6.85-6.78 (m, 1H), 3.90-3.79 (m, 4H), 2.62-2.51 (m, 4H).


Under a nitrogen atmosphere, the Compound of Formula AAD (5.6 g, 26.6 mmol) was dissolved in THF (500 mL) at a temperature of about 25° C. The resulting solution was cooled to −78° C. and LiHMDS (35 mL, 34.6 mmol, 1M in THF) was added to form a reaction mixture. The reaction mixture was stirred at −78° C. for 1.5 h and a THF (100 mL) solution of N-(5-chloro-2-pyridyl)triflimide (also known as Comins' reagent, 10.5 g, 26.6 mmol) was added. The resulting reaction mixture was stirred at −78° C. for 1 h. The reaction mixture was then warmed to about 25° C. over a 1 h period and stirred for an additional 4 h at about 25° C. After this period, the solvent was removed under reduced pressure to provide a residue. The residue was purified by column chromatography on a silica gel column, using a gradient of from 2:98 to 50:50 (by volume) EtOAc:hexane as an eluent, to provide 5.75 g of the triflate Compound of Formula AAE as light yellow oil.


The structure of the Compound of Formula AAE was confirmed by 1H-NMR and mass spectrometry.


Compound of Formula AAE: 1H-NMR (CDCl3) δ: 8.03-7.97 (m, 1H), 7.31-7.22 (m, 1H+CHCl3), 6.83-6.75 (m, 1H), 5.92-5.87 (m, 1H), 4.17-4.12 (m, 2H), 3.77-3.71 (m, 2H), 2.64-2.58 (m, 2H); MS: 327 (M+1).


Under a nitrogen atmosphere, the Compound of Formula AAE (2.1 g, 6.4 mmol), 5-trifluoromethyl-pyridin-2-ylamine (AAF, 2.1 g, 12.8 mmol), and triethylamine (1.96 mL, 1.42 g, 14.2 mmol) were dissolved in THF (30 mL) at a temperature of about 25. The resulting solution was stirred for 2 min. Thereafter, Pd(OAc)2 (287 mg, 1.28 mmol) and Dppp (528 mg, 1.28 mmol) were added to form a reaction mixture. The reaction mixture was flushed with nitrogen gas. The nitrogen atmosphere was removed and replaced by a carbon monoxide atmosphere. The reaction mixture was stirred while heating to 72° C. and stirred at this temperature for 35 minutes. The reaction mixture was then to cooled to about 25° C. The solvent was removed under reduced pressure to provide a residue. The residue was purified by column chromatography on a silica gel column, using a gradient of from 2:98 to 99:1 (by volume) EtOAc:hexane as an eluent, to provide 1.2 g of Cyclo(hetero)alkenyl Compound M2(a) as a white solid.


The structure of Cyclo(hetero)alkenyl Compound M2(a) was confirmed by 1H-NMR and mass spectrometry.


Cyclo(hetero)alkenyl Compound M2(a): 1H-NMR (CD3OD) δ: 8.66-8.60 (m, 1H), 8.40-8.33 (m, 1H), 8.12-7.96 (m, 2H), 7.47-7.36 (m, 1H), 6.95-6.82 (m, 2H), 4.26-4.18 (m, 2H), 3.73-3.64 (m, 2H), 2.68-2.57 (m, 2H); MS: m/z=367.


5.38 Example 38
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula Y34(a)

Compound Y34(a) was prepared according to Example 3, except that 2-chloro-3-fluoropyridine was used in place of 2,3-dichloropyridine.


5.39 Example 39
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula N34(a)

Compound N34(a) was prepared according to Example 1, except that 4-(trifluoromethyl)-N-methylbenzenamine was used in place of 4-(tert-butyl)aniline.


5.40 Example 40
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A45(a)

Compound A45(a) was prepared according to Example 1, except that 2-(4-aminophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol was used in place of 4-(tert-butyl)aniline.


5.41 Example 41
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A226(a)

Compound A226(a) was prepared according to Example 3, except that 2-chloro-3-bromopyridine was used in place of 2,3-dichloropyridine.


5.42 Example 42
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula L8(a)

Compound L8(a) was prepared according to Example 1, except that 3-chloro-4-trifluoromethoxy aniline was used in place of 4-(tert-butyl)aniline.


5.43 Example 43
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A116(a)

Compound A116(a) was prepared according to Example 33, except that 4-(1,1,2,2-tetrafluoroethoxy)phenyl amine was used in place of 5-trifluoromethylpyridin-2-yl amine.


5.44 Example 44
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A118(a)

Compound A118(a) was prepared according to Example 1, except that 4-(1,1-dimethyl-pentyl)phenyl amine was used in place of 4-(tert-butyl)aniline.


5.45 Example 45
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A120(a)

Compound A120(a) was prepared according to Example 1, except that 4-(piperidin-1-yl)benzenamine was used in place of 4-(tert-butyl)aniline.


5.46 Example 46
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula L6(a)

Compound L6(a) was prepared according to Example 1, except that 3-fluoro-4-trifluoromethylphenyl amine was used in place of 4-(tert-butyl)aniline.


5.47 Example 47
Synthesis of a Cyclo(Hetero)Alkenyl Compound of Formula A47(a)

Compound A47(a) was prepared according to Example 1, except that 2-(4-aminophenyl)-2-methylpropionic acid ethyl ester was used in place of 4-(tert-butyl)aniline.


5.48 Example 48
Binding of Cyclo(Hetero)Alkenyl Compounds to mGluR5

The following assay can be used to demonstrate that Cyclo(hetero)alkenyl Compounds bind to and modulate the activity of mGluR5.


Cell Cultures:


Primary glial cultures are prepared from cortices of Sprague-Dawley 18 days old embryos. The cortices are dissected and then dissociated by trituration. The resulting cell homogenate is plated onto poly-D-lysine precoated T175 flasks (BIOCOAT, commercially available from Becton Dickinson and Company Inc. of Franklin Lakes, N.J.) in Dulbecco's Modified Eagle's Medium (“DMEM,” pH 7.4), buffered with 25 mM HEPES, and supplemented with 15% fetal calf serum (“FCS,” commercially available from Hyclone Laboratories Inc. of Omaha, Nebr.), and incubated at 37° C. and 5% CO2. After 24 hours, FCS supplementation is reduced to 10%. On day six, oligodendrocytes and microglia are removed by strongly tapping the sides of the flasks. One day following this purification step, secondary astrocyte cultures are established by subplating onto 96 poly-D-lysine precoated T175 flasks (BIOCOAT) at a density of 65,000 cells/well in DMEM and 10% FCS. After 24 hours, the astrocytes are washed with serum free medium and then cultured in DMEM, without glutamate, supplemented with 0.5% FCS, 20 mM HEPES, 10 ng/mL epidermal growth factor (“EGF”), 1 mM sodium pyruvate, and LX penicillin/streptomycin at pH 7.5 for 3 to 5 days at 37° C. and 5% CO2. The procedure allows the expression of the mGluR5 receptor by astrocytes, as demonstrated by S. Miller et al., J. Neurosci. 15(9):6103-6109 (1995).


Assay Protocol:


After 3-5 days incubation with EGF, the astrocytes are washed with 127 mM NaCl, 5 mM KCl, 2 mM MgCl2, 700 mM NaH2PO4, 2 mM CaCl2, 5 mM NaHCO3, 8 mM HEPES, 10 mM Glucose at pH 7.4 (“Assay Buffer”) and loaded with the dye Fluo-4 (commercially available from Molecular Probes Inc. of Eugene, Oreg.) using 0.1 mL of Assay Buffer containing Fluo-4 (3 mM final). After 90 minutes of dye loading, the cells are then washed twice with 0.2 mL Assay Buffer and resuspended in 0.1 mL of Assay Buffer. The plates containing the astrocytes are then transferred to a Fluorometric Imaging Plate reader (commercially available from Molecular Devices Corporation of Sunnyvale, Calif.) for the assessment of calcium mobilization flux in the presence of glutamate and in the presence or absence of antagonist. After monitoring fluorescence for 15 seconds to establish a baseline, DMSO solutions containing various concentrations of a Cyclo(hetero)alkenyl Compound diluted in Assay Buffer (0.05 mL of 4× dilutions for competition curves) are added to the cell plate and fluorescence is monitored for 2 minutes. 0.05 mL of a 4× glutamate solution (agonist) is then added to each well to provide a final glutamate concentration in each well of 10 mM. Plate fluorescence is then monitored for an additional 60 seconds after agonist addition. The final DMSO concentration in the assay s is 1.0%. In each experiment, fluorescence is monitored as a function of time and the data analyzed using Microsoft Excel and GraphPad Prism. Dose-response curves are fit using a non-linear regression to determine IC50 value. In each experiment, each data point is determined two times.


5.49 Example 49
In Vivo Assays for Prevention Or Treatment of Pain

Test Animals:


Each experiment uses rats weighing between 200-260 g at the start of the experiment. The rats are group-housed and have free access to food and water at all times, except prior to oral administration of a Cyclo(hetero)alkenyl Compound when food is removed for 16 hours before dosing. A control group acts as a comparison to rats treated with a Cyclo(hetero)alkenyl Compound. The control group is administered the carrier for the Cyclo(hetero)alkenyl Compound. The volume of carrier administered to the control group is the same as the volume of carrier and Cyclo(hetero)alkenyl Compound administered to the test group.


Acute Pain:


To assess the actions of the Cyclo(hetero)alkenyl Compounds for the treatment or prevention of acute pain the rat tail flick test can be used. Rats are gently restrained by hand and the tail exposed to a focused beam of radiant heat at a point 5 cm from the tip using a tail flick unit (Model 7360, commercially available from Ugo Basile of Italy). Tail flick latencies are defined as the interval between the onset of the thermal stimulus and the flick of the tail. Animals not responding within 20 seconds are removed from the tail flick unit and assigned a withdrawal latency of 20 seconds. Tail flick latencies are measured immediately before (pre-treatment) and 1, 3, and 5 hours following administration of a Cyclo(hetero)alkenyl Compound. Data are expressed as tail flick latency(s) and the percentage of the maximal possible effect (% MPE), i.e., 15 seconds, is calculated as follows:







%





MPE

=



[


(

post





administration





latency

)

-

(

pre


-


administration





latency

)


]


(

20





s





pre


-


administration





latency

)


×
100





The rat tail flick test is described in F. E. D'Amour et al., “A Method for Determining Loss of Pain Sensation,” J. Pharmacol. Exp. Ther. 72:74-79 (1941).


Acute pain can also be assessed by measuring the animal's response to noxious mechanical stimuli by determining the paw withdrawal threshold (“PWT”), as described below.


Inflammatory Pain:


To assess the actions of the Cyclo(hetero)alkenyl Compounds for the treatment or prevention of inflammatory pain the Freund's complete adjuvant (“FCA”) model of inflammatory pain is used. FCA-induced inflammation of the rat hind paw is associated with the development of persistent inflammatory mechanical hyperalgesia and provides reliable prediction of the anti-hyperalgesic action of clinically useful analgesic drugs (L. Bartho et al., “Involvement of Capsaicin-sensitive Neurones in Hyperalgesia and Enhanced Opioid Antinociception in Inflammation,” Naunyn-Schmiedeberg's Archives of Pharmacol. 342:666-670 (1990)). The left hind paw of each animal is administered a 50 μL intraplantar injection of 50% FCA. 24 hour post injection, the animal is assessed for response to noxious mechanical stimuli by determining the PWT, as described below. Rats are then administered a single injection of 1, 3, 10 or 30 mg/Kg of either a Cyclo(hetero)alkenyl Compound; 30 mg/Kg of a control selected from Celebrex, indomethacin or naproxen; or carrier. Responses to noxious mechanical stimuli are then determined 1, 3, 5 and 24 hours post administration. Percentage reversal of hyperalgesia for each animal is defined as:







%





Reversal

=



[


(

post





administration





PWT

)

-

(

pre


-


administration





PWT

)


]


[


(

baseline





PWT

)

-

(

pre


-


administration





PWT

)


]


×
100





Neuropathic Pain:


To assess the actions of the Cyclo(hetero)alkenyl Compounds for the treatment or prevention of neuropathic pain either the Seltzer model or the Chung model can be used.


In the Seltzer model, the partial sciatic nerve ligation model of neuropathic pain is used to produce neuropathic hyperalgesia in rats (Z. Seltzer et al., “A Novel Behavioral Model of Neuropathic Pain Disorders Produced in Rats by Partial Sciatic Nerve Injury,” Pain 43:205-218 (1990)). Partial ligation of the left sciatic nerve is performed under isoflurane/O2 inhalation anaesthesia. Following induction of anesthesia, the left thigh of the rat is shaved and the sciatic nerve exposed at high thigh level through a small incision and is carefully cleared of surrounding connective tissues at a site near the trocanther just distal to the point at which the posterior biceps semitendinosus nerve branches off of the common sciatic nerve. A 7-0 silk suture is inserted into the nerve with a ⅜ curved, reversed-cutting mini-needle and tightly ligated so that the dorsal ⅓ to ½ of the nerve thickness is held within the ligature. The wound is closed with a single muscle suture (4-0 nylon (Vicryl)) and vetbond tissue glue. Following surgery, the wound area is dusted with antibiotic powder. Sham-treated rats undergo an identical surgical procedure except that the sciatic nerve is not manipulated. Following surgery, animals are weighed and placed on a warm pad until they recover from anesthesia. Animals are then returned to their home cages until behavioral testing begins. The animal is assessed for response to noxious mechanical stimuli by determining PWT, as described below, prior to surgery (baseline), then immediately prior to and 1, 3, and 5 hours after drug administration for rear paw of the animal. Percentage reversal of neuropathic hyperalgesia is defined as:







%





Reversal

=



[


(

post





administration





PWT

)

-

(

pre


-


administration





PWT

)


]


[


(

baseline





PWT

)

-

(

pre


-


administration





PWT

)


]


×
100






In the Chung model, the spinal nerve ligation model of neuropathic pain is used to produce mechanical hyperalgesia, thermal hyperalgesia and tactile allodynia in rats. Surgery is performed under isoflurane/O2 inhalation anaesthesia. Following induction of anaesthesia a 3 cm incision is made and the left paraspinal muscles are separated from the spinous process at the L4-S2 levels. The L transverse process is carefully removed with a pair of small rongeurs to identify visually the L4-L6 spinal nerves. The left L5 (or L5 and L6) spinal nerve(s) is isolated and tightly ligated with silk thread. A complete hemostasis is confirmed and the wound is sutured using non-absorbable sutures, such as nylon sutures or stainless steel staples. Sham-treated rats undergo an identical surgical procedure except that the spinal nerve(s) is not manipulated. Following surgery animals are weighed, administered a subcutaneous (s.c.) injection of saline or ringers lactate, the wound area is dusted with antibiotic powder and they are kept on a warm pad until they recover from the anesthesia. Animals are then be returned to their home cages until behavioral testing begins. The animals are assessed for response to noxious mechanical stimuli by determining PWT, as described below, prior to surgery (baseline), then immediately prior to and 1, 3, and 5 hours after being administered a Cyclo(hetero)alkenyl Compound for the left rear paw of the animal. The animal can also be assessed for response to noxious thermal stimuli or for tactile allodynia, as described below. The Chung model for neuropathic pain is described in S. H. Kim, “An Experimental Model for Peripheral Neuropathy Produced by Segmental Spinal Nerve Ligation in the Rat,” Pain 50(3):355-363 (1992).


Response to Mechanical Stimuli as an Assessment of Mechanical Hyperalgesia:


The paw pressure assay can be used to assess mechanical hyperalgesia. For this assay, hind paw withdrawal thresholds (PWT) to a noxious mechanical stimulus are determined using an analgesymeter (Model 7200, commercially available from Ugo Basile of Italy) as described in C. Stein, “Unilateral Inflammation of the Hindpaw in Rats as a Model of Prolonged Noxious Stimulation: Alterations in Behavior and Nociceptive Thresholds,” Pharmacol. Biochem. and Behavior 31:451-455 (1988). The maximum weight that can be applied to the hind paw is set at 250 g and the end point is taken as complete withdrawal of the paw. PWT is determined once for each rat at each time point and only the affected (ipsilateral) paw is tested.


Response to Thermal Stimuli as an Assessment of Thermal Hyperalgesia:


The plantar test can be used to assess thermal hyperalgesia. For this test, hind paw withdrawal latencies to a noxious thermal stimulus are determined using a plantar test apparatus (commercially available from Ugo Basile of Italy) following the technique described by K. Hargreaves et al., “A New and Sensitive Method for Measuring Thermal Nociception in Cutaneous Hyperalgesia,” Pain 32(1):77-88 (1988). The maximum exposure time is set at 32 seconds to avoid tissue damage and any directed paw withdrawal from the heat source is taken as the end point. Three latencies are determined at each time point and averaged. Only the affected (ipsilateral) paw is tested.


Assessment of Tactile Allodynia:


To assess tactile allodynia, rats are placed in clear, plexiglass compartments with a wire mesh floor and allowed to habituate for a period of at least 15 minutes. After habituation, a series of von Frey monofilaments are presented to the plantar surface of the left (operated) foot of each rat. The series of von Frey monofilaments consists of six monofilaments of increasing diameter, with the smallest diameter fiber presented first. Five trials are conducted with each filament with each trial separated by approximately 2 minutes. Each presentation lasts for a period of 4-8 seconds or until a nociceptive withdrawal behavior is observed. Flinching, paw withdrawal or licking of the paw are considered nociceptive behavioral responses.


5.50 Example 50
In Vivo Assays for Prevention or Treatment of Anxiety

The elevated plus maze test or the shock-probe burying test can be used to assess the anxiolytic activity of Cyclo(hetero)alkenyl Compounds in rats or mice.


The Elevated Plus Maze Test:


The elevated plus maze consists of a platform with 4 arms, two open and two closed (50×10×50 cm enclosed with an open roof). Rats (or mice) are placed in the center of the platform, at the crossroad of the 4 arms, facing one of the closed arms. Time spent in the open arms vs the closed arms and number of open arm entries during the testing period are recorded. This test is conducted prior to drug administration and again after drug administration. Test results are expressed as the mean time spent in open arms and the mean number of entries into open arms. Known anxiolytic drugs increase both the time spent in open arms and number of open arm entries. The elevated plus maze test is described in D. Treit, “Animal Models for the Study of Anti-anxiety Agents: A Review,” Neurosci. & Biobehavioral Reviews 9(2):203-222 (1985).


The Shock-Probe Burying Test:


For the shock-probe burying test the testing apparatus consists of a plexiglass box measuring 40×30×40 cm, evenly covered with approximately 5 cm of bedding material (odor absorbent kitty litter) with a small hole in one end through which a shock probe (6.5 cm long and 0.5 cm in diameter) is inserted. The plexiglass shock probe is helically wrapped with two copper wires through which an electric current is administered. The current is set at 2 mA. Rats are habituated to the testing apparatus for 30 min on 4 consecutive days without the shock probe in the box. On test day, rats are placed in one corner of the test chamber following drug administration. The probe is not electrified until the rat touches it with its snout or fore paws, at which point the rat receives a brief 2 mA shock. The 15 min testing period begins once the rat receives its first shock and the probe remains electrified for the remainder of the testing period. The shock elicits burying behavior by the rat. Following the first shock, the duration of time the rat spends spraying bedding material toward or over the probe with its snout or fore paws (burying behavior) is measured as well as the number of contact-induced shocks the rat receives from the probe. Known anxiolytic drugs reduce the amount of burying behavior. In addition, an index of the rat's reactivity to each shock is scored on a 4 point scale. The total time spent immobile during the 15 min testing period is used as an index of general activity. The shock-probe burying test is described in D. Treit, 1985, supra.


5.51 Example 51
In Vivo Assays for Prevention or Treatment of an Addictive Disorder

The conditioned place preference test or drug self-administration test can be used to assess the ability of Cyclo(hetero)alkenyl Compounds to attenuate the rewarding properties of known drugs of abuse.


The Conditioned Place Preference Test:


The apparatus for the conditioned place preference test consists of two large compartments (45×45×30 cm) made of wood with a plexiglass front wall. These two large compartments are distinctly different. Doors at the back of each large compartment lead to a smaller box (36×18×20 cm) box made of wood, painted grey, with a ceiling of wire mesh. The two large compartments differ in terms of shading (white vs black), level of illumination (the plexiglass door of the white compartment is covered with aluminum foil except for a window of 7×7 cm), texture (the white compartment has a 3 cm thick floor board (40×40 cm) with nine equally spaced 5 cm diameter holes and the black has a wire mesh floor), and olfactory cues (saline in the white compartment and 1 mL of 10% acetic acid in the black compartment). On habituation and testing days, the doors to the small box remain open, giving the rat free access to both large compartments.


The first session that a rat is placed in the apparatus is a habituation session and entrances to the smaller grey compartment remain open giving the rat free access to both large compartments. During habituation, rats generally show no preference for either compartment. Following habituation, rats are given 6 conditioning sessions. Rats are divided into 4 groups: carrier pre-treatment+carrier (control group), Cyclo(hetero)alkenyl Compound pre-treatment+carrier, carrier pre-treatment+morphine, Cyclo(hetero)alkenyl Compound pre-treatment+morphine. During each conditioning session the rat is injected with one of the drug combinations and confined to one compartment for 30 min. On the following day, the rat receives a carrier+carrier treatment and is confined to the other large compartment. Each rat receives three conditioning sessions consisting of 3 drug combination-compartment and 3 carrier-compartment pairings. The order of injections and the drug/compartment pairings are counterbalanced within groups. On the test day, rats are injected prior to testing (30 min to 1 hour) with either morphine or carrier and the rat is placed in the apparatus, the doors to the grey compartment remain open and the rat is allowed to explore the entire apparatus for 20 min. The time spent in each compartment is recorded. Known drugs of abuse increase the time spent in the drug-paired compartment during the testing session. If the Cyclo(hetero)alkenyl Compound blocks the acquisition of morphine conditioned place preference (reward), there will be no difference in time spent in each side in rats pre-treated with a Cyclo(hetero)alkenyl Compound and the group will not be different from the group of rats that was given carrier+carrier in both compartments. Data will be analyzed as time spent in each compartment (drug combination-paired vs carrier-paired). Generally, the experiment is repeated with a minimum of 3 doses of a Cyclo(hetero)alkenyl Compound.


The Drug Self-Administration Test:


The apparatus for the drug self-administration test is a standard commercially available operant conditioning chamber. Before drug trials begin rats are trained to press a lever for a food reward. After stable lever pressing behavior is acquired, rats are tested for acquisition of lever pressing for drug reward. Rats are implanted with chronically indwelling jugular catheters for i.v. administration of compounds and are allowed to recover for 7 days before training begins. Experimental sessions are conducted daily for 5 days in 3 hour sessions. Rats are trained to self-administer a known drug of abuse, such as morphine. Rats are then presented with two levers, an “active” lever and an “inactive” lever. Pressing of the active lever results in drug infusion on a fixed ratio 1 (FR1) schedule (i.e., one lever press gives an infusion) followed by a 20 second time out period (signaled by illumination of a light above the levers). Pressing of the inactive lever results in infusion of excipient. Training continues until the total number of morphine infusions stabilizes to within ±10% per session. Trained rats are then used to evaluate the effect of Cyclo(hetero)alkenyl Compounds pre-treatment on drug self-administration. On test day, rats are pre-treated with a Cyclo(hetero)alkenyl Compound or excipient and then are allowed to self-administer drug as usual. If the Cyclo(hetero)alkenyl Compound blocks the rewarding effects of morphine, rats pre-treated with the Cyclo(hetero)alkenyl Compound will show a lower rate of responding compared to their previous rate of responding and compared to excipient pre-treated rats. Data is analyzed as the change in number of drug infusions per testing session (number of infusions during test session−number of infusions during training session).


5.52 Example 52
Functional Assay for Characterizing mGluR1 Antagonistic Properties

Functional assays for the characterization of mGluR1 antagonistic properties are well known in the art. For example, the following procedure can be used.


A CHO-rat mGluR1 cell line is generated using cDNA encoding rat mGluR1 receptor (M. Masu and S, Nakanishi, Nature 349:760-765 (1991)). The cDNA encoding rat mGluR1 receptor can be obtained from, e.g., Prof. S, Nakanishi (Kyoto, Japan).


40,000 CHO-rat mGluR1 cells/well are plated into a COSTAR 3409, black, clear bottom, 96 well, tissue culture treated plate (commercially available from Fisher Scientific of Chicago, Ill.) and are incubated in Dulbecco's Modified Eagle's Medium (DMEM, pH 7.4) supplemented with glutamine, 10% FBS, 1% Pen/Strep, and 500 μg/mL Geneticin for about 12 h. The CHO-rat mGluR1 cells are then washed and treated with OPTIMEM medium (commercially available from Invitrogen, Carlsbad, Calif.) and incubated for a time period ranging from 1 to 4 hours prior to loading the cells with the dye FLUO-4 (commercially available from Molecular Probes Inc., Eugene, Oreg.). After incubation, the cell plates are washed with loading buffer (127 mM NaCl, 5 mM KCl, 2 mM MgCl2, 700 μM, NaH2PO4, 2 mM CaCl2, 5 mMNaHCO3, 8 mM HEPES, and 10 mM glucose, pH 7.4) and incubated with 3 μM FLUO-4 in 0.1 mL loading buffer for 90 min. The cells are then washed twice with 0.2 mL loading buffer, resuspended in 0.1 mL of loading buffer, and transferred to a Fluorometric Imaging Plate Reader (“FLIPR”) (commercially available from Molecular Devices Corp., Sunnyvale, Calif.) for measurement of calcium mobilization flux in the presence of glutamate and in the presence or absence of a Cyclo(hetero)alkenyl Compound.


To measure calcium mobilization flux, fluoresence is monitored for about 15 s to establish a baseline and DMSO solutions containing various concentrations of a Cyclo(hetero)alkenyl Compound ranging from about 50 μM to about 0.8 nM diluted in loading buffer (0.05 mL of a 4× dilution) are added to the cell plate and fluoresence is monitored for about 2 min. 0.05 mL of a 4× glutamate solution (agonist) is then added to each well to provide a final glutamate concentration in each well of 10 μM and fluoresence is monitored for about 1 additional min. The final DMSO concentration in the assay is 1%. In each experiment fluoresence is monitored as a function of time and the data is analyzed using a non-linear regression to determine the IC50 value. In each experiment each data point is determined twice.


5.53 Example 53
Binding of Cyclo(Hetero)Alkenyl Compounds TO VR1

Methods for demonstrating a compound's ability to inhibit VR1 are known to those skilled in the art, for example, those methods disclosed in U.S. Pat. No. 6,239,267 to Duckworth et al.; U.S. Pat. No. 6,406,908 to McIntyre et al.; or U.S. Pat. No. 6,335,180 to Julius et al.


Binding of Compound A77(a) to VR1: Assay Protocol


Human VR1 Cloning.


Human spinal cord RNA (commercially available from Clontech, Palo Alto, Calif.) was used. Reverse transcription was conducted on 1.0 μg total RNA using Thermoscript Reverse Transcriptase (commercially available from Invitrogen, Carlsbad, Calif.) and oligo dT primers as detailed in its product description. Reverse transcription reactions were incubated at 55° C. for 1 h, heat-inactivated at 85° C. for 5 min, and RNase H-treated at 37° C. for 20 min.


Human VR1 cDNA sequence was obtained by comparison of the human genomic sequence, prior to annotation, to the published rat sequence. Intron sequences were removed and flanking exonic sequences were joined to generate the hypothetical human cDNA. Primers flanking the coding region of human VR1 were designed as follows:









forward primer,


AAGATCTTCGCTGGTTGCACACTGGGCCACA (SEQ ID NO: 1); and





reverse primer,


GAAGATCTTCGGGGACAGTGACGGTTGGATGT (SEQ ID NO: 2).






PCR of VR1 was performed on one tenth of the Reverse transcription reaction mixture using Expand Long Template Polymerase and Expand Buffer 2 in a final volume of 50 μL according to the manufacturer's instructions (Roche Applied Sciences, Indianapolis, Ind.). After denaturation at 94° C. for 2 min PCR amplification was performed for 25 cycles at 94° C. for 15 sec, 58° C. for 30 sec, and 68° C. for 3 min followed by a final incubation at 72° C. for 7 min to complete the amplification. A PCR product of ˜2.8 kb was gel-isolated using a 1.0% agarose, Tris-Acetate gel containing 1.6 g/mL of crystal violet and purified with a S.N.A.P. UV-Free Gel Purification Kit (commercially available from Invitrogen). The VR1 PCR product was cloned into the pIND/V5-His-TOPO vector (commercially available from Invitrogen) according to the manufacturer's instructions. DNA preparations, restriction enzyme digestions, and preliminary DNA sequencing were performed according to standard protocols. Full-length sequencing confirmed the identity of the human VR1.


Generation of Inducible Cell Lines.


Unless noted otherwise, cell culture reagents were purchased from Life Technologies of Rockville, Md. HEK293-EcR cells expressing the ecdysone receptor (commercially available from Invitrogen) were cultured in Growth Medium (Dulbecco's Modified Eagles Medium containing 10% fetal bovine serum (commercially available from HYCLONE, Logan, Utah), 1× penicillin/streptomycin, 1× glutamine, 1 mM sodium pyruvate and 400 μg/mL Zeocin (commercially available from Invitrogen)). The VR1-pIND constructs were transfected into the HEK293-EcR cell line using Fugene transfection reagent (commercially available from Roche Applied Sciences, Basel, Switzerland). After 48 h, cells were transferred to Selection Medium (Growth Medium containing 300 μg/mL G418 (commercially available from Invitrogen)). Approximately 3 weeks later individual Zeocin/G418 resistant colonies were isolated and expanded. To identify functional clones, multiple colonies were plated into 96-well plates and expression was induced for 48 h using Selection Medium supplemented with 5 μM ponasterone A (“PonA”) (commercially available from Invitrogen). On the day of assay, cells were loaded with Fluo-4 (a calcium-sensitive dye that is commercially available from Molecular Probes, Eugene, Oreg.) and CAP-mediated calcium influx was measured using a FLIPR as described below. Functional clones were re-assayed, expanded, and cryopreserved.


pH-Based Assay. Two days prior to performing this assay, cells were seeded on poly-D-lysine-coated 96-well clear-bottom black plates (commercially available from Becton-Dickinson) at 75,000 cells/well in growth media containing 5 μM PonA (commercially available from Invitrogen) to induce expression. On the day of the assay, the plates were washed with 0.2 mL 1× Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 1.6 mM CaCl2 and 20 mM HEPES, pH 7.4 (“wash buffer”), and loaded using 0.1 mL of wash buffer containing Fluo-4 (3 μM final concentration, commercially available from Molecular Probes). After 1 h, the cells were washed twice with 0.2 mL wash buffer and resuspended in 0.05 mL 1× Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 3.5 mM CaCl2 and 10 mM Citrate, pH 7.4 (“assay buffer”). Plates were then transferred to a FLIPR for assay. Compound A77(a) was diluted in assay buffer, and 50 mL of the resultant solution were added to the cell plates and the solution monitored for two minutes. The final concentration of Compound A77(a) ranged from about 50 μM to about 3 M. Agonist buffer (wash buffer titrated with 1N HCl to provide a solution having a pH of 5.5 when mixed 1:1 with assay buffer) (0.1 mL) was then added to each well, and the plates were incubated for 1 additional min. Data were collected over the entire time course and analyzed using Excel and Graph Pad Prism. Compound A77(a) when assayed according to this protocol had an IC50 of 148.1 nM.


Capsaicin-Based Assay.


Two days prior to performing this assay, cells were seeded in poly-D-lysine-coated 96-well clear-bottom black plates (50,000 cells/well) in growth media containing 5 μM PonA (commercially available from Invitrogen) to induce expression. On the day of the assay, the plates were washed with 0.2 mL 1× Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 1 mM CaCl2 and 20 mM HEPES, pH 7.4, and cells were loaded using 0.1 mL of wash buffer containing Fluo-4 (3 μM final). After one h, the cells were washed twice with 0.2 mL of wash buffer and resuspended in 0.1 mL of wash buffer. The plates were transferred to a FLIPR for assay. 50 μL of Compound A77(a) diluted with assay buffer were added to the cell plates and incubated for 2 min. The final concentration of Compound A77(a) ranged from about 50 pM to about 3 μM. Human VR1 was activated by the addition of 50 μL of capsaicin (400 nM), and the plates were incubated for an additional 3 min. Data were collected over the entire time course and analyzed using Excel and GraphPad Prism. Compound A77(a) when assayed according to this protocol had an IC50 of 4.4 nM.


The results of the pH-based assay and the capsaicin-based assay demonstrate that Compound A77(a), an illustrative Cyclo(hetero)alkenyl Compound, binds to and modulates the activity of human VR1 and, accordingly, is useful for treating or preventing pain, UI, an ulcer, IBD or IBS.


The present invention is not to be limited in scope by the specific embodiments disclosed in the examples which are intended as illustrations of a few aspects of the invention and any embodiments that are functionally equivalent are within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art and are intended to fall within the scope of the appended claims.


A number of references have been cited, the entire disclosures of which are incorporated herein by reference.

Claims
  • 1. A compound of formula:
  • 2. The compound of claim 1, wherein Ar2 is
  • 3. The compound of claim 1, wherein Ar1 is
  • 4. The compound of claim 1, wherein each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.
  • 5. The compound of claim 3, wherein each R8 is independently -(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.
  • 6. The compound of claim 1, wherein R4 is —H; R1 is —H, -halo, —CH3, —NO2, —CN, —OH, —OCH3, —NH2, —C(halo)3, —CH(halo)2, or —CH2(halo); and each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —OH, -halo, —N3, —NO2, —N(R7)2, —CH═NR7, —NR7OH, —OR7, —COR7, —C(O)OR7, —OC(O)R7, —OC(O)OR7, —SR7, —S(O)R7, or —S(O)2R7.
  • 7. The compound of claim 6, wherein n or p is 1 and R2 is —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C8-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
  • 8. The compound of claim 6, wherein X is O.
  • 9. The compound of claim 8, wherein Ar1 is pyridyl; n is 1 and R2 is —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C8-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
  • 10. The compound of claim 8, wherein m is 0; n is 0; and Ar1 is
  • 11. The compound of claim 10, wherein R1 is Cl and Ar2 is
  • 12. The compound of claim 11, wherein r is 1 and R8 is halo or —(C1-C6)alkyl.
  • 13. The compound of claim 12, wherein Ar2 is substituted in the 4-position.
  • 14. The compound of claim 13, wherein the —(C1-C6)alkyl is tert-butyl group.
  • 15. The compound of claim 13, wherein R8 is halo.
  • 16. The compound of claim 8, wherein n is 0, m is 1, R1 is —CH3, and Ar1 is pyridyl.
  • 17. The compound of claim 16, wherein Ar2 is
  • 18. The compound of claim 17, wherein r is 1 and R8 is halo or —(C1-C6)alkyl.
  • 19. The compound of claim 17, wherein the —(C1-C6)alkyl is tert-butyl group and Ar2 is substituted at 4-position.
  • 20. The compound of claim 17, wherein R8 is halo.
  • 21. The compound of claim 8, wherein Ar1 is
  • 22. The compound of claim 21, wherein n is 1 and R2 is —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
  • 23. The compound of claim 21, wherein R1 is —F, —Cl, —Br, or —I; n is 0; r is 1 and R8 is -halo.
  • 24. The compound of claim 21, wherein R1 is —F, —Cl, —Br, or —I; n is 0; r is 1 and R8 is —CF3.
  • 25. The compound of claim 21, wherein R1 is —F, —Cl, —Br, or —I; n is 0; r is 1 and R8 is -tert-butyl.
  • 26. The compound of claim 21, wherein R1 is —CF3; n is 0; r is 1 and R8 is -tert-butyl.
  • 27. The compound of claim 21, wherein R1 is —CH3; n is 0; r is 1 and R8 is -halo.
  • 28. The compound of claim 21, wherein R1 is —CF3; n is 0; r is 1 and R8 is -halo.
  • 29. The compound of claim 21, wherein R1 is —CF3; n is 0; r is 1 and R8 is —CH3.
  • 30. The compound of claim 21, wherein n is 0; m is 0; R1 is —CH3; r is 1 and R8 is —CF3.
  • 31. The compound of claim 21, wherein R1 is —CF3; n is 0; r is 1 and R8 is —CF3.
  • 32. The compound of claim 21, wherein R1 is —CH3; n is 0; r is 1 and R8 is -tert-butyl.
  • 33. The compound of claim 1, wherein m is 0; n is 0, Ar1 is
  • 34. The compound of claim 33, wherein R1 is —Cl.
  • 35. The compound of claim 34, wherein Ar2 is
  • 36. The compound of claim 35, wherein r is 1 and R8 is -halo or a —(C1-C6)alkyl.
  • 37. The compound of claim 36, wherein the Ar2 is substituted in the 4-position.
  • 38. The compound of claim 37, wherein the —(C1-C6)alkyl group is a tert-butyl group.
  • 39. The compound of claim 37, wherein R8 is -halo.
  • 40. The compound of claim 39, wherein R8 is —F.
  • 41. The compound of claim 8, wherein Ar1 is
  • 42. The compound of claim 8, wherein Ar1 is
  • 43. The compound of claim 42, wherein n is 1 and R2 is —(C1-C10)alkyl, —(C2-C10)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, —(C8-C14)bicycloalkyl, —(C8-C14)tricycloalkyl, —(C5-C10)cycloalkenyl, —(C8-C14)bicycloalkenyl, —(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
  • 44. The compound of claim 42, wherein R1 is —F, —Cl, —Br, or —I; n is 0; s is 1 and R8 is -halo.
  • 45. The compound of claim 42, wherein R1 is —CH3; n is 0; s is 1 and R8 is -halo.
  • 46. The compound of claim 42, wherein R1 is —CF3; n is 0; s is 1 and R8 is -halo.
  • 47. The compound of claim 42, wherein R1 is —F, —Cl, —Br, or —I; n is 0; s is 1 and R1 is —CH3.
  • 48. The compound of claim 42, wherein R1 is —CH3; n is 0; s is 1 and R is —CH3.
  • 49. The compound of claim 42, wherein R1 is —CF3; n is 0; s is 1 and R8 is —CH3.
  • 50. The compound of claim 42, wherein R1 is —F, —Cl, —Br, or —I; n is 0; s is 1 and R8 is —CF3.
  • 51. The compound of claim 42, wherein R1 is —CH3; n is 0; s is 1 and R8 is —CF3.
  • 52. The compound of claim 42, wherein R1 is —CF3; n is 0; s is 1 and R8 is —CF3.
  • 53. The compound of claim 42, wherein R1 is —F, —Cl, —Br, or —I; n is 0; s is 1 and R8 is —CH2CF3.
  • 54. The compound of claim 42, wherein R1 is —CH3; n is 0; s is 1 and R8 is —CH2CF3.
  • 55. The compound of claim 42, wherein R1 is —CF3; n is 0; s is 1 and R8 is —CH2CF3.
  • 56. The compound of claim 42, wherein R1 is —F, —Cl, —Br, or —I; n is 0; s is 1 and R8 is -tert-butyl.
  • 57. The compound of claim 42, wherein R1 is —CF3; n is 0; s is 1 and R8 is -tert-butyl.
  • 58. The compound of claim 10, wherein Ar2 is
  • 59. The compound of claim 58, wherein R1 is —F, —Cl, —Br, or —I; s is 1 and R8 is -halo.
  • 60. The compound of claim 58, wherein R1 is —F, —Cl, —Br, or —I; s is 1 and R8 is —CF3.
  • 61. The compound of claim 58, wherein R1 is —F, —Cl, —Br, or —I; and R8 is -tert-butyl.
  • 62. The compound of claim 58, wherein R1 is —CF3; s is 1 and R8 is -halo.
  • 63. The compound of claim 58, wherein R1 is —CF3; s is 1 and R8 is —CF3.
  • 64. The compound of claim 58, wherein R1 is —CF3; s is 1 and R8 is -tert-butyl.
  • 65. The compound of claim 58, wherein R1 is —CH3; s is 1 and R8 is -halo.
  • 66. The compound of claim 58, wherein R1 is —CF3; s is 1 and R8 is —CH3.
  • 67. The compound of claim 58, wherein R1 is —CH3; s is 1 and R8 is —CF3.
  • 68. The compound of claim 58, wherein R1 is —CH3; s is 1 and R8 is -tert-butyl.
  • 69. The compound of claim 8, wherein Ar1 is
  • 70. The compound of claim 1, wherein m is 0.
  • 71. The compound of claim 1, wherein Ar1 is a pyridyl group.
  • 72. The compound of claim 1, wherein Ar2 is
  • 73. The compound of claim 72, wherein s is 0 or 1.
  • 74. The compound of claim 1, wherein Ar2 is
  • 75. The compound of claim 74, wherein r is 0 or 1.
  • 76. The compound of claim 1, wherein Ar2 is
  • 77. The compound of claim 76, wherein each R8 is independently —H, halo, —(C1-C6)alkyl, —O(C1-C6)alkyl, —C(halo)3, —CH(halo)2, or —CH2(halo).
  • 78. The compound of claim 77, wherein s is 0, 1 or 2.
  • 79. A composition comprising the compound or a pharmaceutically acceptable salt of the compound of claim 1 and a pharmaceutically acceptable carrier or excipient.
  • 80. A method for treating pain in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of claim 1.
  • 81. A method for making the cyclo(hetero)alkenyl compound of claim 6, comprising allowing a 1-heteroaromatic-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid compound to react with a compound of formula Ar2—NHR4 to provide the cyclo(hetero)alkenyl compound.
  • 82. A method for making the cyclo(hetero)alkenyl compound of claim 6, comprising allowing a 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid amide compound to react with a compound of formula Ar1—Z to provide the cyclo(hetero)alkenyl compound; wherein Z is Cl, Br or I.
Parent Case Info

This application is a continuation of Ser. No. 12/706,571 filed Feb. 16, 2010, now U.S. Pat. No. 8,227,467, which is a continuation of Ser. No. 10/867,546 filed Jun. 14, 2004, now U.S. Pat. No. 7,683,063, which claims the benefit of U.S. Provisional application No. 60/477,744, filed Jun. 12, 2003, the disclosure of which is incorporated by reference herein in its entirety.

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Related Publications (1)
Number Date Country
20130012541 A1 Jan 2013 US
Provisional Applications (1)
Number Date Country
60477744 Jun 2003 US
Continuations (2)
Number Date Country
Parent 12706571 Feb 2010 US
Child 13525950 US
Parent 10867546 Jun 2004 US
Child 12706571 US