Patent Grant
8232290
The present application relates to novel P2X7R antagonists that are indol-3 carboxamide and azaindol-3 carboxamide compounds, pharmaceutical compositions comprising these compounds and to their use in the prophylactic and therapeutic treatment of diseases and disorders mediated by P2X7R.
P2X7R is an ATP-gated ion channel belonging to the P2X ionotropic channel family. The gene was first isolated from rat brain (Surprenant et al. (1996) 272:735-738) and subsequently from a human monocyte library (Rassendren et al. (1997) J. Biol. Chem. 272:5482-5486; Genbank accession numbers NM—002562, Y09561) by virtue of its sequence homology with the other members of the P2X family. It was later found that P2X7R corresponded to the unidentified P2Z receptor which mediates the permeabilising action of ATP on mast cells and macrophages (Dahlqvist and Diamant (1974) Acta Physiol. Scand. 34:368-384; Steinberg and Silverstein (1987) J. Biol. Chem. 262:3118-3122; Gordon (1986) Biochem. J. 233:309-319). The P2X7R has two hydrophobic membrane-spanning domains, an extracellular loop, and forms transmembrane ion channels. P2X7R bears a pharmacological profile markedly different from other P2X homo- or heteromers (North and Surprenant (2000) Annual Rev. Pharmacology Toxicology 40:563-580). P2X7R requires levels of ATP in excess of 1 mM to achieve activation, whereas other P2X receptors activate at ATP concentrations of ≦100 μM (Steinberg et al. (1987) J. Biol. Chem. 262:8884-8888; Greenberg et al. (1988) J. Biol. Chem. 263:10337-10343). While all P2X receptors demonstrate non-selective channel-like properties following ligation, the channels formed by the P2X7R can rapidly transform into pores that can allow the passage of molecules of up to 900 Dalton (Virginio et al. (1999) J. Physiol. 519:335-346).
P2X7R is expressed in haematopoietic cells, mast cells, lymphocytes, erythrocytes, fibroblast, Langerhans cells, and macrophages (Surprenant et al., 1996, Science 272:3118-3122). In the central nervous system, P2X7R expression has been reported in glial cells, Schwann cells, astrocytes, as well as in neurons (Ferrari et al. (1996) J. Immunol 156:1531-1539; Collo et al. (1997) Neuropharmacology 36: 1277-1283; Anderson and Nedergaard (2006) Trends Neuroscien 29: 257-262).
P2X7R is involved in the regulation of the immune function and inflammatory response. Activation of P2X7R by ATP in macrophages is associated with mitogenic stimulation of T cells (Baricordi et al. (1996) Blood 87:682-690), the release of cytokines (Griffiths et al. (1995) J. Immol. 154:2821-2828), and formation of macrophage polykarions (Falzoni et al. (1995) J. Clin. Invest. 95:1207-1216). P2X7R is involved in the processing and release of active interleukin-1beta (IL-1β) from proinflammatory cells (Perregaux and Gabel (1998) J Biol Chem 269:15195-15203; Ferrari et al., (2006) J Immunol 176: 3877-3883). Stimulation of the P2X7R by ATP can also result in apoptosis and cell death by triggering the formation of non-selective plasma membrane pores (Di Virgilio et al. (1998) Cell Death Differ. 5:191-199).
Upregulation of P2X7R has been observed during ischemic damage and necrosis induced by occlusion of middle cerebral artery in rat brain (Collo et al. (1997) Neuropharmacol 36:1277-1283). Recent studies indicate a role of P2X7R in the generation of superoxide in microglia, and upregulation of P2X7R has been detected around amyloid plaques in a transgenic mouse models for Alzheimer's disease (Parvathenani et al. (2003) J Biol Chem 278:13300-13317) and in multiple sclerosis lesions from autopsy brain sections (Narcisse et al. (2005) Glia, 49:245-258).
Studies from mice lacking P2X7R resulted in absence of inflammatory and neuropathic hypersensitivity to mechanical and thermal stimuli, indicating a link between P2X7R and inflammatory and neuropathic pain (Chessell et al. (2005) Pain 114:386-396). Antagonists of P2X7R significantly improved functional recovery and decreased cell death in spinal cord injury in animal models (Wang et al. (2004) Nature Med 10:B21-B27).
Compounds which modulate P2X7R have been reported. For example, Brilliant Blue (Jiang et al., Mol. Phamacol. 58 (2000), 82-88), the isoquinolines 1-[N,O-Bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine and N-[1-[N-methyl-p-(5 isoquinolinesulfonyl)benzyl]-2-(4 phenylpiperazine)ethyl]-5-isoquinolinesulfonamide (Humphreys et al., Mol. Pharmacol., 54 (1998), 22-32), adamantane derivatives (WO 99/29660, WO 99/29661, WO 00/61569, WO 01/42194, WO 01/44170, WO 01/44213, WO 01/94338, WO 03/041707, WO 03/042190, WO 03/080579, WO 04/074224, WO 05/014529, WO 06/025783, WO 06/059945), piperidine and piperazine compounds (WO 01/44213, WO 01/46200, WO 08/005,368), benzamide and heteroarylamide compounds (WO 03/042191, WO 04/058731, WO 04/058270, WO 04/099146, WO 05/019182, WO 06/003500, WO 06/003513, WO 06/067444), substituted tyrosine derivatives (WO 00/71529, WO 03/047515, WO 03/059353), imidazole compounds (WO 05/014555), amino-tetrazoles compounds (WO 05/111003), cyanoamidine (WO 06/017406), bicycloheteroaryl derivatives (WO 05/009968, WO 06/102588, WO 06/102610, WO 07/028.022, WO 07/109,154, WO 07/109,160, WO 07/109,172, WO 07/109,182, WO 07/109,192, WO 07/109,201), acylhydrazide (WO 06/110516), and other examples (WO 99/29686, WO 04/106305, WO 05/039590, WO 06/080884, WO 06/086229, WO 06/136004, WO 07/025,366, WO 07/056.046, WO 07/056.091, WO 07/141,267, WO 07/141,269, WO 08/003,697) are antagonists of P2X7R while Oxidized ATP (oATP) acts as an irreversible inhibitor of the receptor (Chen et al., J. Biol. Chem., 268 (1993), 8199-8203).
Consequently, there is strong evidence that compounds acting on P2X7R can be used in the treatment of pain, inflammatory processes, and degenerative conditions associated with disease states such as rheumatoid arthritis, osteoarthritis, psoriasis, allergic dermatitis, asthma, chronic obstructive pulmonary disease, airways hyper-responsiveness, septic shock, glomerulonephritis, irritable bowel disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, atherosclerosis, growth and metastases of malignant cells, myoblastic leukaemia, diabetes, Alzheimer's disease, Parkinson's disease, multiple sclerosis, glaucoma, depression, bipolar affective disorders, anxiety, meningitis, traumatic brain injury, acute spinal cord injury, neuropathic pain, osteoporosis, burn injury, ischemic heart disease, myocardial infarction, stroke, and varicose veins.
Thus, the object on the present invention is to provide a novel series of compound which can inhibit P2X7R activity and can be used in the treatment of the above mentioned diseases.
The present invention relates to novel P2X7R antagonists that are indol-3 carboxamide and azaindol-3 carboxamide compounds represented by the general formula (I):
wherein,
Compounds of Formula (I), wherein R1 is
a mono- or bicycloalkylalkyl group selected from cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, cycloheptylmethyl, cycloheptylethyl, bicyclo[2.2.2]octan-1-yl methyl and bicyclo[2.2.2]octan-1-ylethyl are preferred.
Compounds as disclosed above, wherein R2 is C1-C5 alkyl or C2-C5 hydroxyalkyl are also preferred.
Furthermore, it is preferred that at least two of R3, R4, R5 and R6 are hydrogen. Additionally, it is preferred that a, b, c, and d are C or one of a, b, c and d is N. Examples of novel indol-3 carboxamide and azaindol-3 carboxamide compounds are disclosed in examples 6-295.
The invention further relates to a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, being:
The present invention also includes isotopically-labelled compounds, which are identical to those recited in Formula (I), but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass 25 number usually found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine and chlorine, such as 2H, 3H, 13C, 14C, 15N, 18O, 17O, 31P, 32P, 35S, 18F, and 35Cl, respectively. Compounds of the present invention, prodrugs thereof, and pharmaceutically acceptable salts of said compounds or of said prodrugs which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labelled compounds of the present invention, for example those into which radioactive isotopes such as 3H and 14C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., 3H, and carbon-14, i.e., 14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., 2H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances.
Isotopically-labelled compounds of Formula (I) of this invention and prodrugs thereof can generally be prepared by carrying out the procedures disclosed in the Examples below, by substituting a readily available isotopically-labelled reagent for a non-isotopically-labelled reagent.
Pharmaceutically acceptable salts include those formed with anions such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with cations such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine and procaine.
Further Pharmaceutically Acceptable Salts
In an further embodiment the present application is directed to a pharmaceutical composition comprising a compound of Formula (I) of the present invention.
The pharmaceutical composition according to the present invention may further comprise an additional active compound in separate or unit dosage form for simultaneous or sequential administration.
The compounds of Formula (I) or a pharmaceutically acceptable salt thereof can be used in the manufacture of a medicament for the prophylactic or therapeutic treatment of any disease state in a human, or other mammal, which is exacerbated or caused by excessive or unregulated cytokine production by such mammal's cells, such as but not limited to monocytes and/or macrophages.
The present invention also relates to the treatment of an IL-1 or cytokine mediated condition.
As defined herein, an “IL-1 mediated condition” and “cytokine mediated condition” includes, but is not limited to, a disease or disorder selected from the group consisting of arthritis (including psoriatic arthritis, Reiter's syndrome, rheumatoid arthritis, gout, traumatic arthritis, rubella arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and acute synovitis), inflammatory bowel disease, Crohn's disease, emphysema, acute respiratory distress syndrome, adult respiratory distress syndrome, asthma, bronchitis chronic obstructive pulmonary disease, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcoidosis, allergic reactions, allergic contact hypersensitivity, eczema, contact dermatitis, psoriasis, sunburn, cancer, tissue ulceration, restenosis, periodontal disease, epidermolysis bullosa, osteoporosis, bone resorption disease, loosening of artificial joint implants, atherosclerosis, aortic aneurysm, congestive heart failure, myocardial infarction, stroke, cerebral ischemia, head trauma, neurotrauma, spinal cord injury, neuro-degenerative disorders, Alzheimer's disease, Parkinson's disease, glaucoma, migraine, depression, peripheral neuropathy, pain, cerebral amyloid angiopathy, nootropic or cognition enhancement, amyotrophic lateral sclerosis, multiple sclerosis, ocular angiogenesis, corneal injury, macular degeneration, corneal scarring, scleritis, abnormal wound healing, burns, autoimmune disorders, Huntington's disease, diabetes, AIDS, cachexia, sepsis, septic shock, endotoxic shock, conjunctivitis shock, gram negative sepsis, toxic shock syndrome, cerebral malaria, cardiac and renal reperfusion injury, thrombosis, glomerularonephritis, graft vs. host reaction, allograft rejection, organ transplant toxicity, ulcerative colitis, or muscle degeneration, in a mammal, including a human, comprising administering to said mammal an amount of a compound to Formula (I), effective in treating such a condition.
The present invention relates to a pharmaceutical composition for the treatment of an IL-1 mediated condition in a mammal, including a human, comprising an amount of a compound of Formula (I), effective in treating such a condition and a pharmaceutically acceptable carrier.
The compounds of the invention are useful for the treatment of rheumatoid arthritis, osteoarthritis, psoriasis, allergic dermatitis, asthma, chronic obstructive pulmonary disease (COPD), hyperresponsiveness of the airway, septic shock, glomerulonephritis, irritable bowel disease, Crohn's disease, ulcerative colitis, atherosclerosis, growth and metastases of malignant cells, myoblastic leukemia, diabetes, Alzheimer's disease, meningitis, osteoporosis, burn injury, ischemic heart disease, stroke and varicose veins.
In another aspect, the invention further provides a pharmaceutical composition for treating osteoarthritis which comprises a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.
The invention further provides a pharmaceutical composition for effecting immunosuppression (e.g. in the treatment of rheumatoid arthritis, irritable bowel disease, atherosclerosis or psoriasis) which comprises aa therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.
The invention also provides a pharmaceutical composition for treating an obstructive airways disease (e.g. asthma or COPD) which comprises a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.
The present invention yet further provides a pharmaceutical composition for treating a mammal susceptible to or afflicted with conditions that are causally related to abnormal activity of the P2X7 receptor, such as neurodegenerative diseases and disorders including, for example, Parkinson's disease, multiple sclerosis, glaucoma, diseases and disorders which are mediated by or result in neuromfiammation such as, for example traumatic brain injury and encephalitis; centrally-mediated neuropsychiatric diseases and disorders such as, for example depression mania, bipolar disease, anxiety, schizophrenia, eating disorders, sleep disorders and cognition disorders, epilepsy and seizure disorders comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.
In particular embodiment the pharmaceutical composition according to the present invention may be used for the treatment of affective disorders. In a preferred embodiment the affective disorder is selected from depression, anxiety, bipolar disorder and schizophrenia.
In an alternative embodiment the pharmaceutical composition according to the present invention is useful for the treatment of neurodegenerative diseases and disorders, diseases and disorders which are mediated by or result in neuroinflammation and centrally-mediated neuropsychiatric diseases and disorders.
Furthermore, the pharmaceutical composition according to the present invention may particularly be useful for the treatment of pain, inflammatory processes, and degenerative conditions. In a more preferred embodiment the inflammatory process is selected from rheumatoid arthritis, osteoporosis and chronic obstructive pulmonary disease.
Moreover, the pharmaceutical composition according to the present invention may be used for the treatment of neuropathic pain.
Dosage, pharmaceutical preparation and delivery of a compound of Formula (I) for use in accordance with the present invention can be formulated in conventional manner according to methods found in the art, using one or more physiological carriers or excipient, see, for example Ansel et al., “Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7th edition, Lippincott Williams & Wilkins Publishers, 1999. Thus, the P2X7R modulating agent and its physiologically acceptable salts and solvates can be formulated for administration by inhalation, insufflation (either through the mouth, or nose), oral, buccal, parenteral, or rectal administration.
For oral administration, the pharmaceutical composition of a compound of Formula (I) can take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutical acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone, hydroxypropyl methylcellulose), fillers (e.g., lactose, microcrystalline cellulose, calcium hydrogen phosphate), lubricants (e.g., magnesium stearate, talc, silica), disintegrants (e.g., potato starch, sodium starch glycolate), or wetting agents (e.g., sodium lauryl sulphate). The pharmaceutical composition can be administered with a physiologically acceptable carrier to a patient, as described herein. In a specific embodiment, the term “pharmaceutically acceptable” means approved by a regulatory agency or other generally recognized pharmacopoeia for use in animals, and more particularly in humans. The term “carrier” refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic is administered. Such pharmaceutical carriers can be sterile 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. Water is a preferred carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium ion, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. These compositions can be in the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained-release formulations and the like. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Examples of suitable pharmaceutical carriers are described in “Remington's Pharmaceutical Sciences” by E.W. Martin. Such compositions will contain a therapeutically effective amount of the aforementioned compounds, preferably in purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the patient. The formulation should suit the mode of administration.
Liquid preparations for oral administration can be in the form of, for example, solutions, syrups, or suspensions, or can be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparation can be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol, syrup, cellulose derivatives, hydrogenated edible fats), emulsifying agents (e.g., lecithin, acacia), non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, fractionated vegetable oils), preservatives (e.g., methyl or propyl-p-hydroxycarbonates, soric acids). The preparations can also contain buffer salts, flavouring, coloring and sweetening agents as deemed appropriate. Preparations for oral administration can be suitably formulated to give controlled release of a compound of Formula (I).
For administration by inhalation, a compound of Formula (I) of the present invention is conveniently delivered in the form of an aerosol spray presentation from a pressurised pack or a nebulizer, with the use of a suitable propellant (e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas). In the case of a pressurised aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, for example, gelatine, for use in an inhaler or insufflator can be formulated containing a powder mix of a compound of Formula (I) and a suitable powder base such as lactose or starch.
A compound of Formula (I) of the present invention can be formulated for parenteral administration by injection, for example, by bolus injection or continuous infusion. Site of injections include intra-venous, intra-peritoneal or sub-cutaneous. Formulations for injection can be presented in units dosage form (e.g., in phial, in multi-dose container), and with an added preservative. A compound of Formula (I) of the present invention can take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and can contain formulatory agents such as suspending, stabilizing, or dispersing agents. Alternatively, the agent can be in powder form for constitution with a suitable vehicle (e.g., sterile pyrogen-free water) before use. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the composition can also include a solubilizing agent and a local anesthetic such as lignocaine to ease 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 lyophilised powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. Where the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the composition is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients can be mixed prior to administration.
A compound of Formula (I) of the present invention can be formulated for transdermal administration. Transdermal compositions are typically formulated as a topical ointment or cream containing the active ingredient(s), generally in an amount ranging from about 0.01 to about 20% by weight, preferably from about 0.1 to about 20% by weight, preferably from about 0.1 to about 10% by weight, and more preferably from about 0.5 to about 15% by weight. When formulated as a ointment, the active ingredients will typically be combined with either a paraffinic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with, for example an oil-in-water cream base. Such transdermal formulations are well-known in the art and generally include additional ingredients to enhance the dermal penetration of stability of the active ingredients or the formulation. All such known transdermal formulations and ingredients are included within the scope of this invention. The compounds of this invention can also be administered by a transdermal device. Accordingly, transdermal administration can be accomplished using a patch either of the reservoir or porous membrane type, or of a solid matrix variety.
The pharmaceutical composition of the invention can be formulated as neutral or salt forms. Pharmaceutically acceptable salts include those formed with anions such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with cations such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, procaine, etc.
A compound of Formula (I) of the present invention can also, if desired, be presented in a pack, or dispenser device which cancontain one or more unit dosage forms containing the said agent. The pack can for example comprise metal or plastic foil, such as blister pack. The pack or dispenser device can be accompanied with instruction for administration.
A compound of Formula (I) of the present invention can be administered as sole active agent or can be adminstered in combination with other agents. These agents include non-steroidal anti-inflammatory drug (NSAIDS) such as celecoxib, rofecoxib, cimicoxib, etoricoxib, lumiracoxib, valdecoxib, deracoxib, N-(2-cyclohexyloxynitrophenyl)methane sulphonamide, COX189, ABT963, JTE-522, GW-406381, LAS-34475, CS-706, PAC-10649, SVT-2016, GW-644784, tenidap, acetylsalicylic acid (aspirin), amoxiprin, benorilate, choline magnesium salicylate, diflunisal, faislamine, methyl salicylate, magnesium salicylate, salicyl salicylate (salsalatee), diclofenac, aceclofenac, acemetacin, bromfenac, etodolac, indometacin, nabumetone, sulindac, tolmetin, ibuprofen, carprofen, fenbufen, fenoprofen, flurbiprofen, ketoprofen, ketorolac, loxoprofen, naproxen, oxaprozin, tiaprofenic acid, suprofen, mefenamic acid, meclofenamic acid, phenylbutazone, azapropazone, metamizole, oxyphenbutazone, sulfinpyrazone, piroxicam, lornoxicam, meloxicam, tenoxicam, nimesulide, licofelone, paracetamol.
A compound of Formula (I) of the present invention can be combined with agents such as TNF-α inhibitors such as anti-TNF monoclonal antibodies (such as Remicade, CDP-870 and D2E7) and TNF receptor immunoglobulin molecules (such as Enbrel), low dose methotrexate, lefunomide; ciclesonide; hydroxychloroquine, d-penicillamine, auranofin or parenteral or oral gold.
A compound of Formula (I) of the present invention can also be administered in combination with an inhibitor of proTNFalpha convertase enzyme (TACE) such as 3-Amino-N-hydroxy-α-(2-methylpropyl)-3-[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]-2-oxo-1-pyrrolidineacetamide, 2(S),3(S)-Piperidinedicarboxamide, N3-hydroxy-1-methyl-N-2-[4-[(2-methyl-4-quinolinyl)methoxy]phenyl], 3-Thiomorpholinecarboxamide, 4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl, 5-Hexenoic acid, 3-[(hydroxyamino)carbonyl]-2-(2-methylpropyl)-6-phenyl-, 2-(2-methylpropyl)-2-(methylsulfonyl)hydrazide, (2R,3S,5E), 2-Piperidinecarboxamide, N,5-dihydroxy-1-[[4-(1-naphthalenylmethoxy)phenyl]sulfonyl]-(2R,5R), Pentanamide, 3-(formylhydroxyamino)-4-methyl-2-(2-methylpropyl)-N-[(1S,2S)-2-methyl-1-[(2-pyridinylamino)carbonyl]butyl]-, (2R,3S),2-Propenamide, N-hydroxy-3-[3-[[(4-methoxyphenyl)sulfonyl](1-methylethyl)amino]phenyl]-3-(3-pyridinyl)-3 (2E), Benzamide, N-(2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl)-4-[(2-methyl-4-quinolinyl)methoxy], Benzamide, N-[(1-acetyl-4-piperidinyl)(2,5-dioxo-4-imidazolidinyl)methyl]-4-[(2-methyl-4-quinolinyl)methoxy], or 2,4-Imidazolidinedione, 5-methyl-5-[[[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]sulfonyl]methyl]. Other examples of TACE inhibitors are described in WO 99/18074, WO 99/65867, U.S. Pat. No. 6,225,311, WO 00/00465, WO 00/09485, WO 98/38179, WO 02/18326, WO 02/096426, WO 03/079986, WO 03/055856, WO 03/053941, WO 03/040103, WO 03/031431, WO 03/024899, WO 03/016248, WO 04/096206, WO 04/033632, WO 04/108086, WO 04/043349, WO 04/032846, WO 04/012663, WO 04/006925, WO 07/016,597.
A compound of Formula (I) of the present invention can also be administered in combination with a corticosteroid such as budesonide, corticosterone, cortisol, cortisone acetate, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, beclometasone, fludrocortisone acetate, deoxycorticosterone acetate(doca), aldosterone.
A compound of Formula (I) of the present invention can further be administered in combination with a β2-adrenergic receptor agonist such as formoterol, salbutamol (albuterol), levalbuterol, terbutaline, pirbuterol, procaterol, metaproterenol, fenoterol, bitolterol mesylate, salmeterol, bambuterol, clenbuterol.
A compound of Formula (I) of the present invention can further be administered in combination with an antidepressant drug such as sertraline, escitalopram, fluoxetine, bupropion, paroxetine, venlafaxine, trazodone, amitriptyline, citalopram, duloxetine, mirtazapine, nortriptyline, imipramine, lithium.
A compound of Formula (I) of the present invention can further be administered in combination with an antipsychotic drug such as chlorpromazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, promazine, triflupromazine, levomepromazine, promethazine, chlorprothixene, flupenthixol, thiothixene, zuclopenthixol, haloperidol, droperidol, pimozide, melperone, benperidol, triperidol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, paliperidone, bifeprunox, aripiprazole.
A compound of Formula (I) of the present invention can also be administered in combination with a leukotriene biosynthesis inhibitor, 5-lipoxygenase (5-LO) inhibitor or 5-lipoxygenase activating protein (FLAP) antagonist, for example, zileuton; ABT-761; fenleuton; tepoxalin; nicaraven; VIA-2291; etalocib; ketoprofen, Abt-79175; Abt-85761; N-(5-substituted) thiophene-2-alkylsulfonamides; TDT-070; licofelone; PEP-03; tenoxicam; 2,6-di-tert-butylphenol hydrazones; methoxytetrahydropyrans such as Zeneca ZD-2138; the compound SB-210661; pyridinyl-substituted 2-cyanonaphthalene compounds such as L-739-010; 2-cyanoquinoline compounds such as L-746-530; indole and quinoline compounds such as MK-591, MK-886, and BAY x 1005.
A compound of Formula (I) of the present invention can be administered in combination with a receptor antagonists for leukotrienes LTB4, LTC4, LTD4, and LTE, for example, phenothiazin-3-ones such as L-651,392; amidino compounds such as CGS-25019c; benzoxalamines such as ontezolast; benzenecarboximidamides such as BIIL 284/260; and compounds such as zafirlukast, ablukast, montelukast, praniukast, verlukast (MK-679), RG-12525, Ro-245913, iralukast (CGP 45715A), and BAY x 7195; masilukast.
A compound of Formula (I) of the present invention can also be administered in combination with a PDE4 inhibitor including inhibitors of the isoform PDE4D. A compound of Formula (I) of the present invention can also be administered in combination with a antihistaminic H1 receptor antagonists including cetirizine, loratadine, desloratadine, fexofenadine, astemizole, azelastine, and chlorpheniramine.
A compound of Formula (I) of the present invention can further be administered in combination with a gastroprotective H2 receptor antagonist.
A compound of Formula (I) of the present invention can yet further be administered in combination with an α1- and α2-adrenoceptor agonist vasoconstrictor sympathomimetic agent, including propylhexedrine, phenylephrine, phenylpropanolamine, pseudoephedrine, naphazoline hydrochloride, oxymetazoline hydrochloride, tetrahydrozoline hydrochloride, xylometazoline hydrochloride, and ethylnorepinephrine hydrochloride.
A compound of Formula (I) of the present invention can be administered in combination with anticholinergic agents including ipratropium bromide; tiotropium bromide; oxitropium bromide; pirenzepine; and telenzepine The present invention still further relates to the combination of a compound of the invention together with a β1- to β4-adrenoceptor agonists including metaproterenol, isoproterenol, isoprenaline, albuterol, salbutamol, formoterol, salmeterol, terbutaline, orciprenaline, bitolterol mesylate, and pirbuterol; or methylxanthanines including theophylline and aminophylline; sodium cromoglycate; or muscarinic receptor (M1, M2, and M3) antagonist.
A compound of Formula (I) of the present invention can be administered in combination with an insulin-like growth factor type I (IGF-1) mimetic.
A compound of Formula (I) of the present invention can be administered in combination with an inhaled glucocorticoid with reduced systemic side effects, including, prednisone, prednisolone, flunisolide, triamcinolone acetonide, beclomethasone dipropionate, budesonide, fluticasone propionate, and mometasone furoate.
A compound of Formula (I) of the present invention can be administered in combination with (a) tryptase inhibitors; (b) platelet activating factor (PAF) antagonists; (c) interleukin converting enzyme (ICE) inhibitors; (d) IMPDH inhibitors; (e) adhesion molecule inhibitors including VLA-4 antagonists; (f) cathepsins; (g) MAP kinase inhibitors; (h) glucose-6 phosphate dehydrogenase inhibitors; (i) kinin-B1- and B2-receptor antagonists; j) anti-gout agents, e.g., colchicine; (k) xanthine oxidase inhibitors, e.g., allopurinol; (I) uricosuric agents, e.g., probenecid, sulfinpyrazone, and benzbromarone; (m) growth hormone secretagogues; (n) transforming growth factor (TGFβ); (o) platelet-derived growth factor (PDGF); (p) fibroblast growth factor, e.g., basic fibroblast growth factor (bFGF); (q) granulocyte macrophage colony stimulating factor (GM-CSF); (r) capsaicin cream; (s) Tachykinin NK1 and NK3 receptor antagonists such as NKP-608C; SB-233412 (talnetant); and D-4418; and (t) elastase inhibitors such as UT-77 and ZD-0892.
A compound of Formula (I) of the present invention can be administered in combination with an inhibitor of matrix metalloproteases (MMPs), i.e., the stromelysins, the collagenases, and the gelatinases, as well as aggrecanase; especially collagenase-1 (MMP-1), collagenase-2 (MMP-8), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), and stromelysin-3 (MMP-11).
A compound of Formula (I) of the present invention can be administered in combination with anticancer agents such as endostatin and angiostatin or cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and farnesyl transferase inhibitors, VEGF inhibitors, COX-2 inhibitors and antimetabolites such as methotrexate antineoplastic agents, especially antimitotic drugs including the vinca alkaloids such as vinblastine and vincristine.
A compound of Formula (I) of the present invention can be administered in combination with antiviral agents such as Viracept, AZT, aciclovir and famciclovir, and antisepsis compounds such as Valant.
A compound of Formula (I) of the present invention can be administered in combination with cardiovascular agents such as calcium channel blockers, lipid lowering agents such as stating, fibrates, beta-blockers, ACE inhibitors, Angiotensin-2 receptor antagonists and platelet aggregation inhibitors.
A compound of Formula (I) of the present invention can be administered in combination with CNS agents such as antidepressants (such as sertraline), anti-Parkinsonian drugs (such as deprenyl, L-dopa, Requip, Mirapex, MAOB inhibitors such as selegine and rasagiline, comP inhibitors such as Tasmar, A-2 inhibitors, dopamine reuptake inhibitors, NMDA antagonists, Nicotine agonists, Dopamine agonists and inhibitors of neuronal nitric oxide synthase), and anti-Alzheimer's drugs such as donepezil, tacrine, COX-2 inhibitors, propentofylline or metrifonate.
A compound of Formula (I) of the present invention can be administered in combination with osteoporosis agents such as roloxifene, droloxifene, lasofoxifene or fosomax and immunosuppressant agents such as FK-506, rapamycin, cyclosporine, azathioprine, and methotrexate.
General Procedure for Preparation of XInt01:
A solution of the indole derivative X (1 eq) in dry dimethylformamide at 0° C. was added to trifluoroacetic anhydride (1.5 eq), stirred, and slowly warmed to room temperature. After completion of the reaction (1 h), the mixture was treated with ice-cold water to obtain a solid. The solid was separated by filtration and washed with water and n-pentane and dried under high vacuum to afford compound XInt01 (80-94% yield).
General procedure for preparation of XY: A solution of XInt01 (1 eq), K2CO3 (5 eq) and alkyl halides Y such as methyl iodide, ethyl iodide, n-propyl bromide, iso-propyl bromide, n-butyl bromide, isobutyl bromide (1.5 eq, 1 h) or O-t-butyldimethylsilyl-2-chloroethanol (10 eq, 24 h) or O-t-butyldimethylsilyl-2-chloropropanol in acetone was stirred and heated to reflux. After completion of the reaction (monitored by thin layer chromatography (TLC)), the mixture was concentrated in vacuo and the residue treated with dichloromethane. The insoluble impurities were removed by filtration and the filtrate was concentrated to afford compound XY (60-95% yield).
General Procedure for Preparation of AFT20 XYZ:
To a mixture of XY (1 eq) and a cyclic derivative Z (1.5 eq) like cyclopentylmethyl amine, cyclopentylethyl amine, cyclohexylmethyl amine, clyclohexylethyl amine, cycloheptylmethyl amine, cycloheptylethyl amine, bicyclo[2.2.2]octan-1-ylmethyl amine, or bicyclo[2.2.2]octan-1-ylethyl amine, in dry THF at −78° C. was added lithium hexamethyldisilazide (3.5 eq). Bicyclo[2.2.2]octan-1-ylmethyl amine was prepared according to the procedures disclosed in Unig and Kahanek (1957) Chem Ber 90:236, Delany and Berchtold (1988) J Org Chem 53:3262-3265, Grob et al. (1958) Helv Chim Acta 41:1191-1197, Whitney et al. (1970) J Med Chem 13:254-260. The resulting solution was warmed to room temperature and subsequently heated to reflux for 16 h. After completion of the reaction (TLC), the mixture was concentrated in vacuo. In case of the non-silyloxyethyl derivatives, the residue was purified either by trituration, column chromatography or preparative HPLC to afford compound XYZ (40-66% yield). In case of the silyloxyethyl compounds, the residue was used in the deprotection step without further purification.
General Procedure for Deprotection of t-butyldimethylsilyl Group:
To a solution of the silyloxyethyl compound (1 eq) in dry tetrahydrofuran at 0° C. was added tetrabutylammonium fluoride (6 eq) and stirred at room temperature for 4 h. The reaction mixture concentrated in vacuo and the residue was purified by column chromatography to afford XYZ (50-60% yield).
Reagents used in the synthesis of the compounds of this invention are available from commercial suppliers such as Sigma-Aldrich, Alfa Aesar, and Sinova. Chemical properties are evaluated by liquid chromatography-tandem mass spectrometry (MS) and/or calculated using CS Chemdraw 8.0 (CambridgeSoft, USA).
General Procedure for Preparation of XYInt01:
To a solution of azaindole derivative X in hexamethylphosphoramide (HMPA) at 0° C., natrium hydrogen (NaH; 1.2 eq) was added and stirred further. After 1 hour, an alkyl halides Y such as methyl iodide, ethyl iodide, n-propyl bromide, iso-propyl bromide, n-butyl bromide, isobutyl bromide (1.5 eq, 1 h) or O-t-butyldimethylsilyl-2-chloroethanol (10 eq, 24 h) or O-t-butyldimethylsilyl-2-chloropropanol (1.5 eq) was added and stirred. After completion of the reaction (monitored by thin layer chromatography (TLC)), the reaction was quenched by ice cold water and extracted with ethyl acetate (EtOAc; 3×). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to leave a residue of crude product. The crude product was purified by column chromatography to afford XYInt01 (75-85% yield).
General Procedure for Preparation of XYInt02:
To a solution of anhydrous AlCl3 (5 eq) in dry dimethylformamide (DMF) at 0° C. (20 mL) a solution of XYInt01 in dimethylformamide and the mixture was stirred further. After 1 hour, trichloroacetyl chloride (5 eq) was added and the mixture was allowed to warm to room temperature. After completion of the reaction (monitored by TLC), the reaction was quenched with ice-cold water and extracted with dimethylformamide (3×). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to leave a residue which was purified by column chromatography to afford XYInt02 (60-70% yield).
General Procedure for Preparation of XYInt03:
To a solution of XYInt02 in THF was added 5N NaOH and the mixture was stirred at room temperature. After completion of the reaction (monitored by TLC), the mixture was concentrated to about 1/4 th of the reaction volume and neutralized with dil. HCl. The precipitate formed was filtered and dried under vacuum to afford XYInt03 (75-85% yield).
General Procedure for Preparation of XYZ:
To a solution of XYInt02 in dry dimethylformamide, 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide.hydrochloride (EDCl.HCl; 1.5 eq), 1-hydroxy-7-azabenzotriazole (HOAt; 1.5 eq), triethanolamine (2 eq) and Z (1.4 eq) like cyclopentylmethyl amine, cyclopentylethyl amine, cyclohexylmethyl amine, clyclohexylethyl amine, cycloheptylmethyl amine, cycloheptylethyl amine, bicyclo[2.2.2]octan-1-ylmethyl amine, or bicyclo[2.2.2]octan-1-ylethyl amine were added and the resulting reaction mixture was stirred at room temperature. After completion of the reaction (TLC), the reaction mixture was treated with water and extracted with dimethylformamide (3×). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to leave a residue which was purified by column chromatography to afford XYZ (40-55% yield).
General Procedure for Deprotection of t-butyldimethylsilyl Group:
To a solution of the silyloxyethyl compound (1 eq) in dry tetrahydrofuran at 0° C. was added tetrabutylammonium fluoride (6 eq) and stirred at room temperature for 4 hour. The reaction mixture concentrated in vacuo and the residue was purified by column chromatography to afford XYZ (50-60% yield).
Inhibition of P2X7R activity by indol-3 carboxamide and azaindol-3 carboxamide compounds of the present invention can be assessed by measuring calcium influx in Hek293 cells (ECACC No. 85120602) which have been stably transfected with a cDNA for the human P2X7R.
The Hek293 cells are human embryo kidney cells that do not express endogenous P2X7R (Surprenant et al. (1996) Science 272:735-738). Hek293 cells expressing P2X7R were generated by lipofectamine transfection of the human P2X7R cDNA (Genbank accession number BC011913) under the control of the human cytomegalovirus immediate-early (CMV) promoter and inserted into the pcDNA3.1 vector (Invitrogen). Cells were cultivated at 37° C. with 8.5% CO2 in Dulbecco's modified eagles medium (DMEM; GibcoBRL/Invitrogen) supplemented with heat-inactivated foetal calf serum (10% v/v), 2 mM L-glutamine, 100 units/ml penicillin, 0.1 mg/ml streptomycin, and 750 μg/ml Geneticin G418 (GibcoBRL/Invitrogen).
Inhibition of Bz-ATP-stimulated P2X7R by test compounds was monitored by measuring changes in calcium influx using the Fluo-4-AM fluorescent dye according to the manufacturer's recommendations (Molecular Devices Corporation, U.S.A.). Briefly, Hek293 cells expressing P2X7R were cultured in 96-well plates at a final density of approximately 10.000 cells per well. On the day of the experiment, the culture medium was completely removed from the wells and cells were washed one time in assay buffer (1× Hank's Balanced Salt (HBSS) solution containing 20 mM Hepes buffer pH 7.4 and 250 mM Probenecid; GibcoBRL/Invitrogen). The cells were incubated in 50 μl of assay buffer containing 100 μM Fluo-4 AM fluorescent dye per well for 1 hour at room temperature. The assay buffer containing the Fluo-4 AM fluorescent dye was then removed, the cells were washed once with assay buffer (without Fluo-4 AM), 100 μl of assay buffer (without Fluo-4 AM) containing the test compounds was then added per well. After a 15 minute incubation, 100 μM Bz-ATP was added and fluorescence was measured in a FlexStation II (Molecular Devices, U.S.A.) according to the following parameters: 485 nm Excitation Wavelength; 525 nm Emission Wavelength; 515 nm Emission Cut-off; 100 μl Pipette Height; 25 μl Transfer Volume; 5 fold Compound Concentration; 3 rate Addition Speed. Test compounds were added at concentrations of 0.013 μM up to 60 μM. The fluorescence data were processed using a lag time of 15 seconds, recording 45 seconds, zero baseline calibrated using 2 points, and % baseline multiplier set at 3. Then, the area of the resulting curve was calculated and the half-maximal inhibitory concentration (IC50) for each test compound was determined using SoftMax Pro software (Molecular Devices, U.S.A.). Compounds of the present invention can inhibit P2X7R activity with an IC50 between 1 μM and 0.001 μM. For example, the IC50 of compound from Example 5 is approximately 0.134 μM.
The effects of indol-3 carboxamide and azaindol-3 carboxamide compounds of the present invention on IL-1 beta secretion is assessed using the human monocyte cell line THP-1 (ATCC Cat #285-IF-100).
Briefly, THP-1 cells are plated in 96 well plates at a concentration of 200,000 cells per well and allowed to differentiate in RPMI-1640 media (ATCC Cat #30-2001) containing 10% FBS, 100 IU/mL penicillin, 100 ug/mL streptomycin, 100 nM PMA (phorbol myristate acetate) for 72 hours. Under these conditions, THP-1 cells differentiate into macrophages expressing endogenous P2X7R. The compounds of the present invention are added to the cells at different concentrations and the differentiated cells are then stimulated for 4 hours with 1 ug/ml LPS (lipopolysaccharide) to activate IL-1 beta transcription (see Humphreys and Dubyak (1998) J Leukoc Biol. 64:265-73). Subsequently, IL-1 beta processing and secretion is stimulated by adding 2 mM ATP for 1 hour. The concentration of IL-1beta in the supernatants is then quantified by ELISA (R&D system) using specific monoclonal anti-human IL-1 beta antibodies according to the manufacturer instructions. More than 90% of the detected protein is biologically active mature IL-1 beta. Observed results were verified statistically using one-way ANOVA tests. Examples of reduced IL-1 beta secretion by the compounds of the invention are illustrated in
This example illustrates the analgesic and anti-inflammatory benefits of the compounds of the present invention using a carrageenan-induced paw edema model of inflammation.
Adult male Sprague Dawley rats were challenged by a subcutaneous injection of carrageenan (1% suspension, 0.1 ml), in the plantar side of the right hind paw. A suspension of the compound in 0.5% methyl cellulose or a vehicle (0.5% methyl cellulose) was administered orally one hour after the carrageenan challenge. The paw was then marked with indelible ink at the level of the lateral malleolus so that the paw can be immersed in the Plethysmometer cell up to this mark. A Plethysmometer allows the measurments of small volume changes in the paw. An hour after compound or vehicle administration (or 2 hr of carrageenan challenge), the plantar test was performed followed by the recording of paw volume.
For the plantar test, each rat was place on preheated glass stand. Both of the hind paws of the animal were stimulated with a radiant heat source. The latency of paw withdrawal from the stimuli was recorded. An increase in the response latency of paw withdrawal is interpreted as an analgesic response. Three trials were given to each animal in order to obtain an average withdrawal latency. The mean Paw Withdrawal Latency (PWL) of test group was compared with the vehicle treated group.
For the paw edema test, the increase in paw volume for each animal is calculated by subtracting left hind paw volume from right hind paw volume (Difference in Paw Volume=Right Hind paw volume−Left hind paw volume). An inhibition of the increase in paw volume is interpreted as an anti inflammatory response. Observed results were verified statistically using ANOVA Tukey's multiple comparison tests. Results are illustrated in
A compound of the present invention was evaluated for increase in the paw withdrawal latency to respond to the heat stimulus which is indicative of an analgesic response.
A compound of the present invention was also evaluated for inhibition of paw edema induced by carrageenan which is interpreted as an anti-inflammatory response.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is methyl iodide and Z is cyclopentylmethyl amine. Formula: C16H20N2O; Molecular Weight: 256.3; Mass/charge ratio: 256.2 (100.0%), 257.2 (18.3%), 258.2 (1.8%); Elemental analysis: C, 74.97; H, 7.86; N, 10.93; O, 6.24.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is methyl iodide and Z is cyclopentylmethyl amine. Formula: C16H19ClN2O; Molecular Weight: 290.8; Mass/charge ratio: 290.1 (100.0%), 292.1 (33.7%), 291.1 (18.3%), 293.1 (6.0%); Elemental analysis: C, 66.09; H, 6.59; Cl, 12.19; N, 9.63; O, 5.50
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is methyl iodide and Z is cyclopentylmethyl amine. Formula: C16H19FN2O; Molecular Weight: 274.3; Mass/charge ratio: 274.1 (100.0%), 275.2 (17.6%), 276.2 (1.7%); Elemental analysis: C, 70.05; H, 6.98; F, 6.93; N, 10.21; O, 5.83.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is methyl iodide and Z is cyclopentylmethyl amine. Formula: C16H19BrN2O; Molecular Weight: 335.2; MS: 335.1/336.1; Mass/charge ratio: 334.1 (100.0%), 336.1 (99.1%), 335.1 (18.3%), 337.1 (17.9%), 338.1 (1.7%); Elemental analysis: C, 57.32; H, 5.71; Br, 23.83; N, 8.36; O, 4.77.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is methyl iodide and Z is cyclopentylmethyl amine. Formula: C17H22N2O; Molecular Weight: 270.4; Mass/charge ratio: 270.2 (100.0%), 271.2 (19.4%), 272.2 (2.0%); Elemental analysis: C, 75.52; H, 8.20; N, 10.36; O, 5.92.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is O-TBS-2-chloroethanol and Z is cyclopentylmethyl amine. Formula: C17H21FN2O2; Molecular Weight: 304.4; Mass/charge ratio: 304.2 (100.0%), 305.2 (19.4%), 306.2 (2.2%); Elemental analysis: C, 67.09; H, 6.95; F, 6.24; N, 9.20; O, 10.51.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-TBS-2-chloroethanol and Z is cyclopentylmethyl amine. Formula: C17H21ClN2O2; Molecular Weight: 320.8; Mass/charge ratio: 320.1 (100.0%), 322.1 (34.2%), 321.1 (19.4%), 323.1 (6.4%); Elemental analysis: C, 63.64; H, 6.60; Cl, 11.05; N, 8.73; O, 9.97.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-TBS-2-chloroethanol and Z is cyclopentylmethyl amine. Formula: C17H21BrN2O2; Molecular Weight: 365.3; Mass/charge ratio: 364.1 (100.0%), 366.1 (99.5%), 365.1 (19.4%), 367.1 (19.1%), 368.1 (2.2%); Elemental analysis: C, 55.90; H, 5.79; Br, 21.88; N, 7.67; O, 8.76.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is methyl iodide and Z is cyclohexylmethyl amine. Formula: C17H22N2O; Molecular Weight: 270.4; Mass/charge ratio: 270.2 (100.0%), 271.2 (19.4%), 272.2 (2.0%); Elemental analysis: C, 75.52; H, 8.20; N, 10.36; O, 5.92.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is methyl iodide and Z is cyclohexylmethyl amine. Formula: C17H21ClN2O; Molecular Weight: 304.8; MS: 305.1/306.1; Mass/charge ratio: 304.1 (100.0%), 306.1 (33.9%), 305.1 (19.4%), 307.1 (6.3%); Elemental analysis: C, 66.99; H, 6.94; Cl, 11.63; N, 9.19; O, 5.25.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is methyl iodide and Z is cyclohexylmethyl amine. Formula: C17H21FN2O; Molecular Weight: 288.4; Mass/charge ratio: 288.2 (100.0%), 289.2 (19.4%), 290.2 (2.0%); Elemental analysis: C, 70.81; H, 7.34; F, 6.59; N, 9.71; O, 5.55.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is methyl iodide and Z is cyclohexylmethyl amine. Formula: C17H21BrN2O; Molecular Weight: 349.3; MS: 351.1/352.1; Mass/charge ratio: 348.1 (100.0%), 350.1 (99.3%), 349.1 (19.4%), 351.1 (19.0%), 352.1 (1.9%); Elemental analysis: C, 58.46; H, 6.06; Br, 22.88; N, 8.02; O, 4.58.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is methyl iodide and Z is cyclohexylmethyl amine. Formula: C18H24N2O; Molecular Weight: 284.4; Mass/charge ratio: 284.2 (100.0%), 285.2 (20.5%), 286.2 (2.2%); Elemental analysis: C, 76.02; H, 8.51; N, 9.85; O, 5.63.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is O-TBS-2-chloroethanol and Z is cyclohexylmethyl amine. Formula: C18H23FN2O2; Molecular Weight: 318.4; Mass/charge ratio: 318.2 (100.0%), 319.2 (20.5%), 320.2 (2.4%); Elemental analysis: C, 67.90; H, 7.28; F, 5.97; N, 8.80; O, 10.05.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-TBS-2-chloroethanol and Z is cyclohexylmethyl amine. Formula: C18H23ClN2O2; Molecular Weight: 334.8; Mass/charge ratio: 334.1 (100.0%), 336.1 (32.5%), 335.1 (20.3%), 337.1 (6.6%), 336.2 (1.9%); Elemental analysis: C, 64.57; H, 6.92; Cl, 10.59; N, 8.37; O, 9.56.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-TBS-2-chloroethanol and Z is cyclohexylmethyl amine. Formula: C18H23BrN2O2; Molecular Weight: 379.3; Mass/charge ratio: 378.1 (100.0%), 380.1 (99.7%), 379.1 (20.5%), 381.1 (20.2%), 382.1 (2.4%); Elemental analysis: C, 57.00; H, 6.11; Br, 21.07; N, 7.39; O, 8.44.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H24N2O; Molecular Weight: 284.4; Mass/charge ratio: 284.2 (100.0%), 285.2 (20.5%), 286.2 (2.2%); Elemental analysis: C, 76.02; H, 8.51; N, 9.85; O, 5.63.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23ClN2O; Molecular Weight: 318.8; MS: 319.2/320.1; Mass/charge ratio: 318.1 (100.0%), 320.1 (32.0%), 319.2 (19.8%), 321.2 (6.5%), 320.2 (2.2%); Elemental analysis: C, 67.81; H, 7.27; Cl, 11.12; N, 8.79; O, 5.02.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23FN2O; Molecular Weight: 302.4; Mass/charge ratio: 302.2 (100.0%), 303.2 (20.5%), 304.2 (2.2%); Elemental analysis: C, 71.50; H, 7.67; F, 6.28; N, 9.26; O, 5.29.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23BrN2O; Molecular Weight: 363.3; MS: 364.1/365.1; Mass/charge ratio: 362.1 (100.0%), 364.1 (99.5%), 363.1 (20.5%), 365.1 (20.1%), 366.1 (2.2%); Elemental analysis: C, 59.51; H, 6.38; Br, 21.99; N, 7.71; O, 4.40.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H26N2O; Molecular Weight: 298.4; MS: 299.1; Mass/charge ratio: 298.2 (100.0%), 299.2 (21.6%), 300.2 (2.4%); Elemental analysis: C, 76.47; H, 8.78; N, 9.39; O, 5.36.
Synthesised according to the procedure disclosed in Example 1 where X is 4-metoxy indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H26N2O2; Molecular Weight: 314.4; Mass/charge ratio: 314.2 (100.0%), 315.2 (21.7%), 316.2 (2.6%); Elemental analysis: C, 72.58; H, 8.33; N, 8.91; O, 10.18.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H23N3O; Molecular Weight: 309.4; Mass/charge ratio: 309.2 (100.0%), 310.2 (22.0%), 311.2 (2.5%); Elemental analysis: C, 73.76; H, 7.49; N, 13.58; O, 5.17.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H23F3N2O; Molecular Weight: 352.4; Mass/charge ratio: 352.2 (100.0%), 353.2 (21.6%), 354.2 (2.4%); Elemental analysis: C, 64.76; H, 6.58; F, 16.17; N, 7.95; O, 4.54.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H26N2O; Molecular Weight: 298.4; Mass/charge ratio: 298.2 (100.0%), 299.2 (21.6%), 300.2 (2.4%); Elemental analysis: C, 76.47; H, 8.78; N, 9.39; O, 5.36.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25FN2O; Molecular Weight: 316.4; Mass/charge ratio: 316.2 (100.0%), 317.2 (21.6%), 318.2 (2.4%); Elemental analysis: C, 72.12; H, 7.96; F, 6.00; N, 8.85; O, 5.06.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O; Molecular Weight: 332.9; Mass/charge ratio: 332.2 (100.0%), 334.2 (34.4%), 333.2 (21.6%), 335.2 (7.1%); Elemental analysis: C, 68.56; H, 7.57; Cl, 10.65; N, 8.42; O, 4.81.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O; Molecular Weight: 377.3; Mass/charge ratio: 376.1 (100.0%), 378.1 (99.7%), 377.1 (21.6%), 379.1 (21.2%), 380.1 (2.4%); Elemental analysis: C, 60.48; H, 6.68; Br, 21.18; N, 7.42; O, 4.24.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H28N2O; Molecular Weight: 312.4; Mass/charge ratio: 312.2 (100.0%), 313.2 (22.7%), 314.2 (2.7%); Elemental analysis: C, 76.88; H, 9.03; N, 8.97; O, 5.12.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methoxy indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H28N2O2; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.8%), 330.2 (2.9%); Elemental analysis: C, 73.14; H, 8.59; N, 8.53; O, 9.74.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H25N3O; Molecular Weight: 323.4; Mass/charge ratio: 323.2 (100.0%), 324.2 (23.1%), 325.2 (2.7%); Elemental analysis: C, 74.27; H, 7.79; N, 12.99; O, 4.95.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H25F3N2O; Molecular Weight: 366.4; Mass/charge ratio: 366.2 (100.0%), 367.2 (22.7%), 368.2 (2.7%); Elemental analysis: C, 65.56; H, 6.88; F, 15.55; N, 7.65; O, 4.37.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H28N2O; Molecular Weight: 312.4; Mass/charge ratio: 312.2 (100.0%), 313.2 (22.7%), 314.2 (2.7%); Elemental analysis: C, 76.88; H, 9.03; N, 8.97; O, 5.12.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H27FN2O; Molecular Weight: 330.4; Mass/charge ratio: 330.2 (100.0%), 331.2 (22.7%), 332.2 (2.7%); Elemental analysis: C, 72.70; H, 8.24; F, 5.75; N, 8.48; O, 4.84.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H27ClN2O; Molecular Weight: 346.9; Mass/charge ratio: 346.2 (100.0%), 348.2 (34.6%), 347.2 (22.7%), 349.2 (7.5%); Elemental analysis: C, 69.25; H, 7.85; Cl, 10.22; N, 8.08; O, 4.61.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H27BrN2O; Molecular Weight: 391.3; Mass/charge ratio: 390.1 (100.0%), 392.1 (99.9%), 391.1 (22.7%), 393.1 (22.3%), 394.1 (2.6%); Elemental analysis: C, 61.38; H, 6.95; Br, 20.42; N, 7.16; O, 4.09.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H30N2O; Molecular Weight: 326.5; Mass/charge ratio: 326.2 (100.0%), 327.2 (23.8%), 328.2 (2.9%); Elemental analysis: C, 77.26; H, 9.26; N, 8.58; O, 4.90.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methoxy indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H30N2O2; Molecular Weight: 342.5; Mass/charge ratio: 342.2 (100.0%), 343.2 (23.9%), 344.2 (3.1%); Elemental analysis: C, 73.65; H, 8.83; N, 8.18; O, 9.34.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H27N3O; Molecular Weight: 337.5; Mass/charge ratio: 337.2 (100.0%), 338.2 (24.2%), 339.2 (3.0%); Elemental analysis: C, 74.74; H, 8.06; N, 12.45; O, 4.74.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is n-propyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H27F3N2O; Molecular Weight: 380.4; Mass/charge ratio: 380.2 (100.0%), 381.2 (23.8%), 382.2 (2.9%); Elemental analysis: C, 66.30; H, 7.15; F, 14.98; N, 7.36; O, 4.21.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is isopropyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H27ClN2O; Molecular Weight: 346.9; Mass/charge ratio: 346.2 (100.0%), 348.2 (34.6%), 347.2 (22.7%), 349.2 (7.5%); Elemental analysis: C, 69.25; H, 7.85; Cl, 10.22; N, 8.08; O, 4.61.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is isopropyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H27BrN2O; Molecular Weight: 391.3; Mass/charge ratio: 390.1 (100.0%), 392.1 (99.9%), 391.1 (22.7%), 393.1 (22.3%), 394.1 (2.6%); Elemental analysis: C, 61.38; H, 6.95; Br, 20.42; N, 7.16; O, 4.09.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is isopropyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H30N2O; Molecular Weight: 326.5; Mass/charge ratio: 326.2 (100.0%), 327.2 (23.8%), 328.2 (2.9%); Elemental analysis: C, 77.26; H, 9.26; N, 8.58; O, 4.90.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is isobutyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H29ClN2O; Molecular Weight: 360.9; Mass/charge ratio: 360.2 (100.0%), 362.2 (34.9%), 361.2 (23.8%), 363.2 (7.9%); Elemental analysis: C, 69.88; H, 8.10; Cl, 9.82; N, 7.76; O, 4.43.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is isobutyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H29BrN2O; Molecular Weight: 405.4; Mass/charge ratio: 404.1 (100.0%), 406.1 (97.4%), 405.1 (23.5%), 407.1 (22.9%), 406.2 (2.7%), 408.2 (2.5%); Elemental analysis: C, 62.22; H, 7.21; Br, 19.71; N, 6.91; O, 3.95.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is isobutyl bromide, and Z is cycloheptylmethyl amine. Formula: C22H32N2O; Molecular Weight: 340.5; Mass/charge ratio: 340.3 (100.0%), 341.3 (24.2%), 342.3 (3.2%); Elemental analysis: C, 77.60; H, 9.47; N, 8.23; O, 4.70.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H26N2O2; Molecular Weight: 314.4; Mass/charge ratio: 314.2 (100.0%), 315.2 (21.7%), 316.2 (2.6%); Elemental analysis: C, 72.58; H, 8.33; N, 8.91; O, 10.18.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25FN2O2; Molecular Weight: 332.4; Mass/charge ratio: 332.2 (100.0%), 333.2 (21.7%), 334.2 (2.6%); Elemental analysis: C, 68.65; H, 7.58; F, 5.72; N, 8.43; O, 9.63.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O2; Molecular Weight: 348.9; MS: 349.2/350.2; Mass/charge ratio: 348.2 (100.0%), 350.2 (34.6%), 349.2 (21.7%), 351.2 (7.2%); Elemental analysis: C, 65.41; H, 7.22; Cl, 10.16; N, 8.03; O, 9.17.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O2; Molecular Weight: 393.3; MS: 393.2/394.2; Mass/charge ratio: 392.1 (100.0%), 394.1 (99.9%), 393.1 (21.7%), 395.1 (21.3%), 396.1 (2.6%); Elemental analysis: C, 58.02; H, 6.41; Br, 20.32; N, 7.12; O, 8.14.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H28N2O2; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.8%), 330.2 (2.9%); Elemental analysis: C, 73.14; H, 8.59; N, 8.53; O, 9.74.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methoxy indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H28N2O3; Molecular Weight: 344.4; Mass/charge ratio: 344.2 (100.0%), 345.2 (22.8%), 346.2 (3.1%); Elemental analysis: C, 69.74; H, 8.19; N, 8.13; O, 13.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H25N3O2; Molecular Weight: 339.4; Mass/charge ratio: 339.2 (100.0%), 340.2 (23.1%), 341.2 (3.0%); Elemental analysis: C, 70.77; H, 7.42; N, 12.38; O, 9.43.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H25F3N2O2; Molecular Weight: 382.4; Mass/charge ratio: 382.2 (100.0%), 383.2 (22.7%), 384.2 (2.9%); Elemental analysis: C, 62.81; H, 6.59; F, 14.90; N, 7.33; O, 8.37.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is n-butyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H30N2O; Molecular Weight: 326.5; Mass/charge ratio: 326.2 (100.0%), 327.2 (23.8%), 328.2 (2.9%); Elemental analysis: C, 77.26; H, 9.26; N, 8.58; O, 4.90.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is n-butyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H29FN2O; Molecular Weight: 344.5; Mass/charge ratio: 344.2 (100.0%), 345.2 (23.8%), 346.2 (2.9%); Elemental analysis: C, 73.22; H, 8.49; F, 5.52; N, 8.13; O, 4.64.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is n-butyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H29ClN2O; Molecular Weight: 360.9; Mass/charge ratio: 360.2 (100.0%), 362.2 (34.9%), 361.2 (23.8%), 363.2 (7.9%); Elemental analysis: C, 69.88; H, 8.10; Cl, 9.82; N, 7.76; O, 4.43.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is n-butyl bromide, and Z is cycloheptylmethyl amine. Formula: C21H29BrN2O; Molecular Weight: 405.4; Mass/charge ratio: 404.1 (100.0%), 406.1 (97.4%), 405.1 (23.5%), 407.1 (22.9%), 406.2 (2.7%), 408.2; Elemental analysis: C, 62.22; H, 7.21; Br, 19.71; N, 6.91; O, 3.95.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is n-butyl bromide, and Z is cycloheptylmethyl amine. Formula: C22H32N2O; Molecular Weight: 340.5; Mass/charge ratio: 340.3 (100.0%), 341.3 (24.2%), 342.3 (3.2%); Elemental analysis: C, 77.60; H, 9.47; N, 8.23; O, 4.70.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloropropanol, and Z is cycloheptylmethyl amine. Formula: C20H27FN2O2; Molecular Weight: 346.4; Mass/charge ratio: 346.2 (100.0%), 347.2 (22.8%), 348.2 (2.9%); Elemental analysis: C, 69.34; H, 7.86; F, 5.48; N, 8.09; O, 9.24.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-t-butyldimethylsilyl-2-chloropropanol, and Z is cycloheptylmethyl amine. Formula: C20H27ClN2O2; Molecular Weight: 362.9; Mass/charge ratio: 362.2 (100.0%), 364.2 (34.8%), 363.2 (22.8%), 365.2 (7.5%); Elemental analysis: C, 66.19; H, 7.50; Cl, 9.77; N, 7.72; O, 8.82.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-t-butyldimethylsilyl-2-chloropropanol, and Z is cycloheptylmethyl amine. Formula: C20H27BrN2O2; Molecular Weight: 407.3; Mass/charge ratio: 408.1 (100.0%), 406.1 (99.8%), 407.1 (22.7%), 409.1 (22.4%), 410.1 (2.8%); Elemental analysis: C, 58.97; H, 6.68; Br, 19.62; N, 6.88; O, 7.86.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H24N2O; Molecular Weight: 296.4; Mass/charge ratio: 296.2 (100.0%), 297.2 (21.6%), 298.2 (2.4%); Elemental analysis: C, 76.99; H, 8.16; N, 9.45; O, 5.40.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23ClN2O; Molecular Weight: 330.9; MS: 331.2/332.2; Mass/charge ratio: 330.1 (100.0%), 332.1 (32.0%), 331.2 (20.9%), 333.2 (6.9%), 332.2 (2.4%); Elemental analysis: C, 68.97; H, 7.01; Cl, 10.72; N, 8.47; O, 4.84.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23FN2O; Molecular Weight: 314.4; Mass/charge ratio: 314.2 (100.0%), 315.2 (21.6%), 316.2 (2.4%); Elemental analysis: C, 72.58; H, 7.37; F, 6.04; N, 8.91; O, 5.09.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23BrN2O; Molecular Weight: 375.3; MS: 375.1/376.1; Mass/charge ratio: 374.1 (100.0%), 376.1 (99.7%), 375.1 (21.6%), 377.1 (21.2%), 378.1 (2.4%); Elemental analysis: C, 60.81; H, 6.18; Br, 21.29; N, 7.46; O, 4.26.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H26N2O; Molecular Weight: 310.4; MS: 311.1; Mass/charge ratio: 310.2 (100.0%), 311.2 (22.7%), 312.2 (2.7%); Elemental analysis: C, 77.38; H, 8.44; N, 9.02; O, 5.15.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methoxy indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H26N2O2; Molecular Weight: 326.4; Mass/charge ratio: 326.2 (100.0%), 327.2 (22.7%), 328.2 (2.9%); Elemental analysis: C, 73.59; H, 8.03; N, 8.58; O, 9.80.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H23N3O; Molecular Weight: 321.4; Mass/charge ratio: 321.2 (100.0%), 322.2 (23.0%), 323.2 (2.7%); Elemental analysis: C, 74.74; H, 7.21; N, 13.07; O, 4.98.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H23F3N2O; Molecular Weight: 364.4; Mass/charge ratio: 364.2 (100.0%), 365.2 (22.7%), 366.2 (2.7%); Elemental analysis: C, 65.92; H, 6.36; F, 15.64; N, 7.69; O, 4.39.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H26N2O; Molecular Weight: 310.4; Mass/charge ratio: 310.2 (100.0%), 311.2 (22.7%), 312.2 (2.7%); Elemental analysis: C, 77.38; H, 8.44; N, 9.02; O, 5.15.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25FN2O; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.7%), 330.2 (2.7%); Elemental analysis: C, 73.14; H, 7.67; F, 5.78; N, 8.53; O, 4.87.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O; Molecular Weight: 344.9; Mass/charge ratio: 344.2 (100.0%), 346.2 (34.6%), 345.2 (22.7%), 347.2 (7.5%); Elemental analysis: C, 69.65; H, 7.31; Cl, 10.28; N, 8.12; O, 4.64.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O; Molecular Weight: 389.3; Mass/charge ratio: 388.1 (100.0%), 390.1 (99.9%), 389.1 (22.7%), 391.1 (22.3%), 392.1 (2.6%); Elemental analysis: C, 61.70; H, 6.47; Br, 20.52; N, 7.20; O, 4.11.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N20; Molecular Weight: 324.5; Mass/charge ratio: 324.2 (100.0%), 325.2 (23.8%), 326.2 (2.9%); Elemental analysis: C, 77.74; H, 8.70; N, 8.63; O, 4.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methoxy indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O2; Molecular Weight: 340.5; Mass/charge ratio: 340.2 (100.0%), 341.2 (23.8%), 342.2 (3.1%); Elemental analysis: C, 74.08; H, 8.29; N, 8.23; O, 9.40.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H25N3O; Molecular Weight: 335.4; Mass/charge ratio: 335.2 (100.0%), 336.2 (24.1%), 337.2 (3.0%); Elemental analysis: C, 75.19; H, 7.51; N, 12.53; O, 4.77.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H25F3N2O; Molecular Weight: 378.4; Mass/charge ratio: 378.2 (100.0%), 379.2 (23.8%), 380.2 (2.9%); Elemental analysis: C, 66.65; H, 6.66; F, 15.06; N, 7.40; O, 4.23.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O; Molecular Weight: 324.5; Mass/charge ratio: 324.2 (100.0%), 325.2 (23.8%), 326.2 (2.9%); Elemental analysis: C, 77.74; H, 8.70; N, 8.63; O, 4.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27FN2O; Molecular Weight: 342.5; Mass/charge ratio: 342.2 (100.0%), 343.2 (23.8%), 344.2 (2.9%); Elemental analysis: C, 73.65; H, 7.95; F, 5.55; N, 8.18; O, 4.67.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27ClN2O; Molecular Weight: 358.9; Mass/charge ratio: 358.2 (100.0%), 360.2 (34.9%), 359.2 (23.8%), 361.2 (7.9%); Elemental analysis: C, 70.28; H, 7.58; Cl, 9.88; N, 7.81; O, 4.46.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27BrN2O; Molecular Weight: 403.4; MS: 405.1/406.2; Mass/charge ratio: 404.1 (100.0%), 402.1 (99.8%), 403.1 (23.8%), 405.1 (23.4%), 406.1 (2.8%); Elemental analysis: C, 62.53; H, 6.75; Br, 19.81; N, 6.95; O, 3.97.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H30N2O; Molecular Weight: 338.5; Mass/charge ratio: 338.2 (100.0%), 339.2 (24.9%), 340.2 (3.2%); Elemental analysis: C, 78.06; H, 8.93; N, 8.28; O, 4.73.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methoxy indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H30N2O2; Molecular Weight: 354.5; Mass/charge ratio: 354.2 (100.0%), 355.2 (25.0%), 356.2 (3.4%); Elemental analysis: C, 74.54; H, 8.53; N, 7.90; O, 9.03.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H27N3O; Molecular Weight: 349.5; Mass/charge ratio: 349.2 (100.0%), 350.2 (25.3%), 351.2 (3.3%); Elemental analysis: C, 75.61; H, 7.79; N, 12.02; O, 4.58.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is n-propyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H27F3N2O; Molecular Weight: 392.5; Mass/charge ratio: 392.2 (100.0%), 393.2 (24.9%), 394.2 (3.2%); Elemental analysis: C, 67.33; H, 6.93; F, 14.52; N, 7.14; O, 4.08.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is isopropyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O; Molecular Weight: 324.5; Mass/charge ratio: 324.2 (100.0%), 325.2 (23.8%), 326.2 (2.9%); Elemental analysis: C, 77.74; H, 8.70; N, 8.63; O, 4.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is isopropyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27FN2O; Molecular Weight: 342.5; Mass/charge ratio: 342.2 (100.0%), 343.2 (23.8%), 344.2 (2.9%); Elemental analysis: C, 73.65; H, 7.95; F, 5.55; N, 8.18; O, 4.67.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is isopropyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27ClN2O; Molecular Weight: 358.9; Mass/charge ratio: 358.2 (100.0%), 360.2 (34.9%), 359.2 (23.8%), 361.2 (7.9%); Elemental analysis: C, 70.28; H, 7.58; Cl, 9.88; N, 7.81; O, 4.46.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is isopropyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27BrN2O; Molecular Weight: 403.4; Mass/charge ratio: 404.1 (100.0%), 402.1 (99.8%), 403.1 (23.8%), 405.1 (23.4%), 406.1 (2.8%); Elemental analysis: C, 62.53; H, 6.75; Br, 19.81; N, 6.95; O, 3.97.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is isopropyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H30N2O; Molecular Weight: 338.5; Mass/charge ratio: 338.2 (100.0%), 339.2 (24.9%), 340.2 (3.2%); Elemental analysis: C, 78.06; H, 8.93; N, 8.28; O, 4.73.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is isobutyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H29FN2O; Molecular Weight: 356.5; Mass/charge ratio: 356.2 (100.0%), 357.2 (24.9%), 358.2 (3.2%); Elemental analysis: C, 74.12; H, 8.20; F, 5.33; N, 7.86; O, 4.49.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is isobutyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H29ClN2O; Molecular Weight: 372.9; Mass/charge ratio: 372.2 (100.0%), 374.2 (35.1%), 373.2 (24.9%), 375.2 (8.2%), 376.2 (1.0%); Elemental analysis: C, 70.85; H, 7.84; Cl, 9.51; N, 7.51; O, 4.29.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is isobutyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H29BrN2O; Molecular Weight: 417.4; Mass/charge ratio: 416.1 (100.0%), 418.1 (97.5%), 417.1 (24.5%), 419.1 (23.9%), 418.2 (3.0%), 420.2 (2.7%); Elemental analysis: C, 63.31; H, 7.00; Br, 19.14; N, 6.71; O, 3.83.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is isobutyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C23H32N2O; Molecular Weight: 352.5; Mass/charge ratio: 352.3 (100.0%), 353.3 (25.3%), 354.3 (3.5%); Elemental analysis: C, 78.36; H, 9.15; N, 7.95; O, 4.54.
Synthesised according to the procedure disclosed in Example 1 where X is indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H26N2O2; Molecular Weight: 326.4; Mass/charge ratio: 326.2 (100.0%), 327.2 (22.7%), 328.2 (2.9%); Elemental analysis: C, 73.59; H, 8.03; N, 8.58; O, 9.80.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25FN2O2; Molecular Weight: 344.4; Mass/charge ratio: 344.2 (100.0%), 345.2 (22.7%), 346.2 (2.9%); Elemental analysis: C, 69.74; H, 7.32; F, 5.52; N, 8.13; O, 9.29.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O2; Molecular Weight: 360.9; MS: 361.2/362.1; Mass/charge ratio: 360.2 (100.0%), 362.2 (34.8%), 361.2 (22.7%), 363.2 (7.5%); Elemental analysis: C, 66.56; H, 6.98; Cl, 9.82; N, 7.76; O, 8.87.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O2; Molecular Weight: 405.3; Mass/charge ratio: 406.1 (100.0%), 404.1 (99.8%), 405.1 (22.7%), 407.1 (22.3%), 408.1 (2.8%); Elemental analysis: C, 59.26; H, 6.22; Br, 19.71; N, 6.91; O, 7.89.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O2; Molecular Weight: 340.5; Mass/charge ratio: 340.2 (100.0%), 341.2 (23.8%), 342.2 (3.1%); Elemental analysis: C, 74.08; H, 8.29; N, 8.23; O, 9.40.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methoxy indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O3; Molecular Weight: 356.5; Mass/charge ratio: 356.2 (100.0%), 357.2 (23.9%), 358.2 (3.3%); Elemental analysis: C, 70.76; H, 7.92; N, 7.86; O, 13.47.
Synthesised according to the procedure disclosed in Example 1 where X is 4-cyano indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H25N3O2; Molecular Weight: 351.4; Mass/charge ratio: 351.2 (100.0%), 352.2 (24.2%), 353.2 (3.2%); Elemental analysis: C, 71.77; H, 7.17; N, 11.96; O, 9.10.
Synthesised according to the procedure disclosed in Example 1 where X is 4-trifluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H25F3N2O2; Molecular Weight: 394.4; Mass/charge ratio: 394.2 (100.0%), 395.2 (23.8%), 396.2 (3.1%); Elemental analysis: C, 63.95; H, 6.39; F, 14.45; N, 7.10; O, 8.11.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is n-butyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H29FN2O; Molecular Weight: 356.5; Mass/charge ratio: 356.2 (100.0%), 357.2 (24.9%), 358.2 (3.2%); Elemental analysis: C, 74.12; H, 8.20; F, 5.33; N, 7.86; O, 4.49.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is n-butyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H29ClN2O; Molecular Weight: 372.9; Mass/charge ratio: 372.2 (100.0%), 374.2 (35.1%), 373.2 (24.9%), 375.2 (8.2%), 376.2 (1.0%); Elemental analysis: C, 70.85; H, 7.84; Cl, 9.51; N, 7.51; O, 4.29.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is n-butyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H29BrN2O; Molecular Weight: 417.4; Mass/charge ratio: 416.1 (100.0%), 418.1 (97.5%), 417.1 (24.5%), 419.1 (23.9%), 418.2 (3.0%), 420.2 (2.7%); Elemental analysis: C, 63.31; H, 7.00; Br, 19.14; N, 6.71; O, 3.83.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is n-butyl bromide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C23H32N2O; Molecular Weight: 352.5; Mass/charge ratio: 352.3 (100.0%), 353.3 (25.3%), 354.3 (3.5%); Elemental analysis: C, 78.36; H, 9.15; N, 7.95; O, 4.54.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloropropanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27FN2O2; Molecular Weight: 358.4; Mass/charge ratio: 358.2 (100.0%), 359.2 (23.8%), 360.2 (3.1%); Elemental analysis: C, 70.37; H, 7.59; F, 5.30; N, 7.82; O, 8.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-t-butyldimethylsilyl-2-chloropropanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27ClN2O2; Molecular Weight: 374.9; Mass/charge ratio: 374.2 (100.0%), 376.2 (35.1%), 375.2 (23.8%), 377.2 (7.9%), 378.2 (1.0%); Elemental analysis: C, 67.28; H, 7.26; Cl, 9.46; N, 7.47; O, 8.54.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-t-butyldimethylsilyl-2-chloropropanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27BrN2O2; Molecular Weight: 419.4; Mass/charge ratio: 420.1 (100.0%), 418.1 (99.6%), 419.1 (23.7%), 421.1 (23.4%), 422.1 (3.1%); Elemental analysis: C, 60.15; H, 6.49; Br, 19.05; N, 6.68; O, 7.63.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is O-t-butyldimethylsilyl-2-chloropropanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H30N2O2; Molecular Weight: 354.5; Mass/charge ratio: 354.2 (100.0%), 355.2 (25.0%), 356.2 (3.4%); Elemental analysis: C, 74.54; H, 8.53; N, 7.90; O, 9.03.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is methyl iodide, and Z is clyclohexylethyl amine. Formula: C18H23ClN2O; Molecular Weight: 318.8; Mass/charge ratio: 318.1 (100.0%), 320.1 (32.0%), 319.2 (19.8%), 321.2 (6.5%), 320.2 (2.2%); Elemental analysis: C, 67.81; H, 7.27; Cl, 11.12; N, 8.79; O, 5.02.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is methyl iodide, and Z is clyclohexylethyl amine. Formula: C18H23FN2O; Molecular Weight: 302.4; Mass/charge ratio: 302.2 (100.0%), 303.2 (20.5%), 304.2 (2.2%); Elemental analysis: C, 71.50; H, 7.67; F, 6.28; N, 9.26; O, 5.29.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is methyl iodide, and Z is clyclohexylethyl amine. Formula: C18H23BrN2O; Molecular Weight: 363.3; Mass/charge ratio: 362.1 (100.0%), 364.1 (99.5%), 363.1 (20.5%), 365.1 (20.1%), 366.1 (2.2%); Elemental analysis: C, 59.51; H, 6.38; Br, 21.99; N, 7.71; O, 4.40.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is methyl iodide, and Z is clyclohexylethyl amine. Formula: C19H26N2O; Molecular Weight: 298.4; Mass/charge ratio: 298.2 (100.0%), 299.2 (21.6%), 300.2 (2.4%); Elemental analysis: C, 76.47; H, 8.78; N, 9.39; O, 5.36.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is ethyl iodide, and Z is clyclohexylethyl amine. Formula: C19H25FN2O; Molecular Weight: 316.4; Mass/charge ratio: 316.2 (100.0%), 317.2 (21.6%), 318.2 (2.4%); Elemental analysis: C, 72.12; H, 7.96; F, 6.00; N, 8.85; O, 5.06.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is ethyl iodide, and Z is clyclohexylethyl amine. Formula: C19H25ClN2O; Molecular Weight: 332.9; Mass/charge ratio: 332.2 (100.0%), 334.2 (34.4%), 333.2 (21.6%), 335.2 (7.1%); Elemental analysis: C, 68.56; H, 7.57; Cl, 10.65; N, 8.42; O, 4.81.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is ethyl iodide, and Z is clyclohexylethyl amine. Formula: C19H25BrN2O; Molecular Weight: 377.3; Mass/charge ratio: 376.1 (100.0%), 378.1 (99.7%), 377.1 (21.6%), 379.1 (21.2%), 380.1 (2.4%); Elemental analysis: C, 60.48; H, 6.68; Br, 21.18; N, 7.42; O, 4.24.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is ethyl iodide, and Z is clyclohexylethyl amine. Formula: C20H28N2O; Molecular Weight: 312.4; Mass/charge ratio: 312.2 (100.0%), 313.2 (22.7%), 314.2 (2.7%); Elemental analysis: C, 76.88; H, 9.03; N, 8.97; O, 5.12.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is clyclohexylethyl amine. Formula: C19H25FN2O2; Molecular Weight: 332.4; Mass/charge ratio: 332.2 (100.0%), 333.2 (21.7%), 334.2 (2.6%); Elemental analysis: C, 68.65; H, 7.58; F, 5.72; N, 8.43; O, 9.63.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is clyclohexylethyl amine. Formula: C19H25ClN2O2; Molecular Weight: 348.9; Mass/charge ratio: 348.2 (100.0%), (34.6%), 349.2 (21.7%), 351.2 (7.2%); Elemental analysis: C, 65.41; H, 7.22; Cl, 10.16; N, 8.03; O, 9.17.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is clyclohexylethyl amine. Formula: C19H25BrN2O2; Molecular Weight: 393.3; Mass/charge ratio: 392.1 (100.0%), (99.9%), 393.1 (21.7%), 395.1 (21.3%), 396.1 (2.6%); Elemental analysis: C, 58.02; H, 6.41; Br, 20.32; N, 7.12; O, 8.14.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is clyclohexylethyl amine. Formula: C20H28N2O2; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.8%), 330.2 (2.9%); Elemental analysis: C, 73.14; H, 8.59; N, 8.53; O, 9.74.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is methyl iodide, and Z is cycloheptylethyl amine. Formula: C19H25ClN2O; Molecular Weight: 332.9; Mass/charge ratio: 332.2 (100.0%), 334.2 (34.4%), 333.2 (21.6%), 335.2 (7.1%); Elemental analysis: C, 68.56; H, 7.57; Cl, 10.65; N, 8.42; O, 4.81.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is methyl iodide, and Z is cycloheptylethyl amine. Formula: C19H25BrN2O; Molecular Weight: 377.3; Mass/charge ratio: 376.1 (100.0%), 378.1 (99.7%), 377.1 (21.6%), 379.1 (21.2%), 380.1 (2.4%); Elemental analysis: C, 60.48; H, 6.68; Br, 21.18; N, 7.42; O, 4.24.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is methyl iodide, and Z is cycloheptylethyl amine. Formula: C20H28N2O; Molecular Weight: 312.4; Mass/charge ratio: 312.2 (100.0%), 313.2 (22.7%), 314.2 (2.7%); Elemental analysis: C, 76.88; H, 9.03; N, 8.97; O, 5.12.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is ethyl iodide, and Z is cycloheptylethyl amine. Formula: C20H27ClN2O; Molecular Weight: 346.9; Mass/charge ratio: 346.2 (100.0%), 348.2 (34.6%), 347.2 (22.7%), 349.2 (7.5%); Elemental analysis: C, 69.25; H, 7.85; Cl, 10.22; N, 8.08; O, 4.61.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is ethyl iodide, and Z is cycloheptylethyl amine. Formula: C20H27BrN2O; Molecular Weight: 391.3; Mass/charge ratio: 390.1 (100.0%), 392.1 (99.9%), 391.1 (22.7%), 393.1 (22.3%), 394.1 (2.6%); Elemental analysis: C, 61.38; H, 6.95; Br, 20.42; N, 7.16; O, 4.09.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is ethyl iodide, and Z is cycloheptylethyl amine. Formula: C21H30N2O; Molecular Weight: 326.5; Mass/charge ratio: 326.2 (100.0%), 327.2 (23.8%), 328.2 (2.9%); Elemental analysis: C, 77.26; H, 9.26; N, 8.58; O, 4.90.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylethyl amine. Formula: C20H27ClN2O2; Molecular Weight: 362.9; Mass/charge ratio: 362.2 (100.0%), 364.2 (34.8%), 363.2 (22.8%), 365.2 (7.5%); Elemental analysis: C, 66.19; H, 7.50; Cl, 9.77; N, 7.72; O, 8.82.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylethyl amine. Formula: C20H27BrN2O2; Molecular Weight: 407.3; Mass/charge ratio: 408.1 (100.0%), 406.1 (99.8%), 407.1 (22.7%), 409.1 (22.4%), 410.1 (2.8%); Elemental analysis: C, 58.97; H, 6.68; Br, 19.62; N, 6.88; O, 7.86.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylethyl amine. Formula: C21H30N2O2; Molecular Weight: 342.5; Mass/charge ratio: 342.2 (100.0%), 343.2 (23.9%), 344.2 (3.1%); Elemental analysis: C, 73.65; H, 8.83; N, 8.18; O, 9.34.
Synthesised according to the procedure disclosed in Example 1 where X is 5-chloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23ClN2O; Molecular Weight: 318.8; Mass/charge ratio: 318.1 (100.0%), 320.1 (32.0%), 319.2 (19.8%), 321.2 (6.5%), 320.2 (2.2%); Elemental analysis: C, 67.81; H, 7.27; Cl, 11.12; N, 8.79; O, 5.02.
Synthesised according to the procedure disclosed in Example 1 where X is 5-bromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23BrN2O; Molecular Weight: 363.3; Mass/charge ratio: 362.1 (100.0%), 364.1 (99.5%), 363.1 (20.5%), 365.1 (20.1%), 366.1 (2.2%); Elemental analysis: C, 59.51; H, 6.38; Br, 21.99; N, 7.71; O, 4.40.
Synthesised according to the procedure disclosed in Example 1 where X is 5-methyl indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H26N2O; Molecular Weight: 298.4; Mass/charge ratio: 298.2 (100.0%), 299.2 (21.6%), 300.2 (2.4%); Elemental analysis: C, 76.47; H, 8.78; N, 9.39; O, 5.36.
Synthesised according to the procedure disclosed in Example 1 where X is 5-chloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O; Molecular Weight: 332.9; Mass/charge ratio: 332.2 (100.0%), 334.2 (34.4%), 333.2 (21.6%), 335.2 (7.1%); Elemental analysis: C, 68.56; H, 7.57; Cl, 10.65; N, 8.42; O, 4.81.
Synthesised according to the procedure disclosed in Example 1 where X is 5-bromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O; Molecular Weight: 377.3; Mass/charge ratio: 376.1 (100.0%), 378.1 (99.7%), 377.1 (21.6%), 379.1 (21.2%), 380.1 (2.4%); Elemental analysis: C, 60.48; H, 6.68; Br, 21.18; N, 7.42; O, 4.24.
Synthesised according to the procedure disclosed in Example 1 where X is 5-methyl indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H28N2O; Molecular Weight: 312.4; Mass/charge ratio: 312.2 (100.0%), 313.2 (22.7%), 314.2 (2.7%); Elemental analysis: C, 76.88; H, 9.03; N, 8.97; O, 5.12.
Synthesised according to the procedure disclosed in Example 1 where X is 5-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O2; Molecular Weight: 348.9; Mass/charge ratio: 348.2 (100.0%), (34.6%), 349.2 (21.7%), 351.2 (7.2%); Elemental analysis: C, 65.41; H, 7.22; Cl, 10.16; N, 8.03; O, 9.17.
Synthesised according to the procedure disclosed in Example 1 where X is 5-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O2; Molecular Weight: 393.3; Mass/charge ratio: 392.1 (100.0%), (99.9%), 393.1 (21.7%), 395.1 (21.3%), 396.1 (2.6%); Elemental analysis: C, 58.02; H, 6.41; Br, 20.32; N, 7.12; O, 8.14.
Synthesised according to the procedure disclosed in Example 1 where X is 5-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H28N2O2; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.8%), 330.2 (2.9%); Elemental analysis: C, 73.14; H, 8.59; N, 8.53; O, 9.74.
Synthesised according to the procedure disclosed in Example 1 where X is 6-chloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23ClN2O; Molecular Weight: 318.8; Mass/charge ratio: 318.1 (100.0%), 320.1 (32.0%), 319.2 (19.8%), 321.2 (6.5%), 320.2 (2.2%); Elemental analysis: C, 67.81; H, 7.27; Cl, 11.12; N, 8.79; O, 5.02.
Synthesised according to the procedure disclosed in Example 1 where X is 6-bromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23BrN2O; Molecular Weight: 363.3; Mass/charge ratio: 362.1 (100.0%), 364.1 (99.5%), 363.1 (20.5%), 365.1 (20.1%), 366.1 (2.2%); Elemental analysis: C, 59.51; H, 6.38; Br, 21.99; N, 7.71; O, 4.40.
Synthesised according to the procedure disclosed in Example 1 where X is 6-methyl indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H26N2O; Molecular Weight: 298.4; Mass/charge ratio: 298.2 (100.0%), 299.2 (21.6%), 300.2 (2.4%); Elemental analysis: C, 76.47; H, 8.78; N, 9.39; O, 5.36.
Synthesised according to the procedure disclosed in Example 1 where X is 6-chloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O; Molecular Weight: 332.9; Mass/charge ratio: 332.2 (100.0%), 334.2 (34.4%), 333.2 (21.6%), 335.2 (7.1%); Elemental analysis: C, 68.56; H, 7.57; Cl, 10.65; N, 8.42; O, 4.81.
Synthesised according to the procedure disclosed in Example 1 where X is 6-bromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25BrN20; Molecular Weight: 377.3; Mass/charge ratio: 376.1 (100.0%), 378.1 (99.7%), 377.1 (21.6%), 379.1 (21.2%), 380.1 (2.4%); Elemental analysis: C, 60.48; H, 6.68; Br, 21.18; N, 7.42; O, 4.24.
Synthesised according to the procedure disclosed in Example 1 where X is 6-methyl indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H28N2O; Molecular Weight: 312.4; Mass/charge ratio: 312.2 (100.0%), 313.2 (22.7%), 314.2 (2.7%); Elemental analysis: C, 76.88; H, 9.03; N, 8.97; O, 5.12.
Synthesised according to the procedure disclosed in Example 1 where X is 6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O2; Molecular Weight: 348.9; Mass/charge ratio: 348.2 (100.0%), 350.2 (34.6%), 349.2 (21.7%), 351.2 (7.2%); Elemental analysis: C, 65.41; H, 7.22; Cl, 10.16; N, 8.03; O, 9.17.
Synthesised according to the procedure disclosed in Example 1 where X is 6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O2; Molecular Weight: 393.3; Mass/charge ratio: 392.1 (100.0%), 394.1 (99.9%), 393.1 (21.7%), 395.1 (21.3%), 396.1 (2.6%); Elemental analysis: C, 58.02; H, 6.41; Br, 20.32; N, 7.12; O, 8.14.
Synthesised according to the procedure disclosed in Example 1 where X is 6-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H28N2O2; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.8%), 330.2 (2.9%); Elemental analysis: C, 73.14; H, 8.59; N, 8.53; O, 9.74.
Synthesised according to the procedure disclosed in Example 1 where X is 7-chloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23ClN2O; Molecular Weight: 318.8; Mass/charge ratio: 318.1 (100.0%), 320.1 (32.0%), 319.2 (19.8%), 321.2 (6.5%), 320.2 (2.2%); Elemental analysis: C, 67.81; H, 7.27; Cl, 11.12; N, 8.79; O, 5.02.
Synthesised according to the procedure disclosed in Example 1 where X is 7-bromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H23BrN2O; Molecular Weight: 363.3; Mass/charge ratio: 362.1 (100.0%), 364.1 (99.5%), 363.1 (20.5%), 365.1 (20.1%), 366.1 (2.2%); Elemental analysis: C, 59.51; H, 6.38; Br, 21.99; N, 7.71; O, 4.40.
Synthesised according to the procedure disclosed in Example 1 where X is 7-methyl indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H26N2O; Molecular Weight: 298.4; Mass/charge ratio: 298.2 (100.0%), 299.2 (21.6%), 300.2 (2.4%); Elemental analysis: C, 76.47; H, 8.78; N, 9.39; O, 5.36.
Synthesised according to the procedure disclosed in Example 1 where X is 7-chloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O; Molecular Weight: 332.9; Mass/charge ratio: 332.2 (100.0%), 334.2 (34.4%), 333.2 (21.6%), 335.2 (7.1%); Elemental analysis: C, 68.56; H, 7.57; Cl, 10.65; N, 8.42; O, 4.81.
Synthesised according to the procedure disclosed in Example 1 where X is 7-bromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O; Molecular Weight: 377.3; Mass/charge ratio: 376.1 (100.0%), 378.1 (99.7%), 377.1 (21.6%), 379.1 (21.2%), 380.1 (2.4%); Elemental analysis: C, 60.48; H, 6.68; Br, 21.18; N, 7.42; O, 4.24.
Synthesised according to the procedure disclosed in Example 1 where X is 7-methyl indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H28N20; Molecular Weight: 312.4; Mass/charge ratio: 312.2 (100.0%), 313.2 (22.7%), 314.2 (2.7%); Elemental analysis: C, 76.88; H, 9.03; N, 8.97; O, 5.12.
Synthesised according to the procedure disclosed in Example 1 where X is 7-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O2; Molecular Weight: 348.9; Mass/charge ratio: 348.2 (100.0%), (34.6%), 349.2 (21.7%), 351.2 (7.2%); Elemental analysis: C, 65.41; H, 7.22; Cl, 10.16; N, 8.03; O, 9.17.
Synthesised according to the procedure disclosed in Example 1 where X is 7-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O2; Molecular Weight: 393.3; Mass/charge ratio: 392.1 (100.0%), (99.9%), 393.1 (21.7%), 395.1 (21.3%), 396.1 (2.6%); Elemental analysis: C, 58.02; H, 6.41; Br, 20.32; N, 7.12; O, 8.14.
Synthesised according to the procedure disclosed in Example 1 where X is 7-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H28N2O2; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.8%), 330.2 (2.9%); Elemental analysis: C, 73.14; H, 8.59; N, 8.53; O, 9.74.
Synthesised according to the procedure disclosed in Example 1 where X is 5-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23ClN2O; Molecular Weight: 330.9; Mass/charge ratio: 330.1 (100.0%), 332.1 (32.0%), 331.2 (20.9%), 333.2 (6.9%), 332.2 (2.4%); Elemental analysis: C, 68.97; H, 7.01; Cl, 10.72; N, 8.47; O, 4.84.
Synthesised according to the procedure disclosed in Example 1 where X is 5-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23BrN2O; Molecular Weight: 375.3; Mass/charge ratio: (100.0%), 376.1 (99.7%), 375.1 (21.6%), 377.1 (21.2%), 378.1 (2.4%); Elemental analysis: C, 60.81; H, 6.18; Br, 21.29; N, 7.46; O, 4.26.
Synthesised according to the procedure disclosed in Example 1 where X is 5-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H26N2O; Molecular Weight: 310.4; Mass/charge ratio: (100.0%), 311.2 (22.7%), 312.2 (2.7%); Elemental analysis: C, 77.38; H, 8.44; N, 9.02; O, 5.15.
Synthesised according to the procedure disclosed in Example 1 where X is 5-chloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O; Molecular Weight: 344.9; Mass/charge ratio: 344.2 (100.0%), 346.2 (34.6%), 345.2 (22.7%), 347.2 (7.5%); Elemental analysis: C, 69.65; H, 7.31; Cl, 10.28; N, 8.12; O, 4.64.
Synthesised according to the procedure disclosed in Example 1 where X is 5-bromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O; Molecular Weight: 389.3; Mass/charge ratio: 388.1 (100.0%), 390.1 (99.9%), 389.1 (22.7%), 391.1 (22.3%), 392.1 (2.6%); Elemental analysis: C, 61.70; H, 6.47; Br, 20.52; N, 7.20; O, 4.11.
Synthesised according to the procedure disclosed in Example 1 where X is 5-methyl indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O; Molecular Weight: 324.5; Mass/charge ratio: 324.2 (100.0%), 325.2 (23.8%), 326.2 (2.9%); Elemental analysis: C, 77.74; H, 8.70; N, 8.63; O, 4.93.
Synthesised according to the procedure disclosed in Example 1 where X is 5-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O2; Molecular Weight: 360.9; Mass/charge ratio: 360.2 (100.0%), 362.2 (34.8%), 361.2 (22.7%), 363.2 (7.5%); Elemental analysis: C, 66.56; H, 6.98; Cl, 9.82; N, 7.76; O, 8.87.
Synthesised according to the procedure disclosed in Example 1 where X is 5-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O2; Molecular Weight: 405.3; Mass/charge ratio: 406.1 (100.0%), 404.1 (99.8%), 405.1 (22.7%), 407.1 (22.3%), 408.1 (2.8%); Elemental analysis: C, 59.26; H, 6.22; Br, 19.71; N, 6.91; O, 7.89.
Synthesised according to the procedure disclosed in Example 1 where X is 5-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O2; Molecular Weight: 340.5; Mass/charge ratio: 340.2 (100.0%), 341.2 (23.8%), 342.2 (3.1%); Elemental analysis: C, 74.08; H, 8.29; N, 8.23; O, 9.40.
Synthesised according to the procedure disclosed in Example 1 where X is 6-chloro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23ClN2O; Molecular Weight: 330.9; Mass/charge ratio: 330.1 (100.0%), 332.1 (32.0%), 331.2 (20.9%), 333.2 (6.9%), 332.2 (2.4%); Elemental analysis: C, 68.97; H, 7.01; Cl, 10.72; N, 8.47; O, 4.84.
Synthesised according to the procedure disclosed in Example 1 where X is 6-bromo indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23BrN2O; Molecular Weight: 375.3; Mass/charge ratio: 374.1 (100.0%), 376.1 (99.7%), 375.1 (21.6%), 377.1 (21.2%), 378.1 (2.4%); Elemental analysis: C, 60.81; H, 6.18; Br, 21.29; N, 7.46; O, 4.26.
Synthesised according to the procedure disclosed in Example 1 where X is 6-methyl indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H26N2O; Molecular Weight: 310.4; Mass/charge ratio: 310.2 (100.0%), 311.2 (22.7%), 312.2 (2.7%); Elemental analysis: C, 77.38; H, 8.44; N, 9.02; O, 5.15.
Synthesised according to the procedure disclosed in Example 1 where X is 6-chloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O; Molecular Weight: 344.9; Mass/charge ratio: 344.2 (100.0%), 346.2 (34.6%), 345.2 (22.7%), 347.2 (7.5%); Elemental analysis: C, 69.65; H, 7.31; Cl, 10.28; N, 8.12; O, 4.64.
Synthesised according to the procedure disclosed in Example 1 where X is 6-bromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O; Molecular Weight: 389.3; Mass/charge ratio: 388.1 (100.0%), 390.1 (99.9%), 389.1 (22.7%), 391.1 (22.3%), 392.1 (2.6%); Elemental analysis: C, 61.70; H, 6.47; Br, 20.52; N, 7.20; O, 4.11.
Synthesised according to the procedure disclosed in Example 1 where X is 6-methyl indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O; Molecular Weight: 324.5; Mass/charge ratio: 324.2 (100.0%), 325.2 (23.8%), 326.2 (2.9%); Elemental analysis: C, 77.74; H, 8.70; N, 8.63; O, 4.93.
Synthesised according to the procedure disclosed in Example 1 where X is 6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O2; Molecular Weight: 360.9; Mass/charge ratio: (100.0%), 362.2 (34.8%), 361.2 (22.7%), 363.2 (7.5%); Elemental analysis: C, 66.56; H, 6.98; Cl, 9.82; N, 7.76; O, 8.87.
Synthesised according to the procedure disclosed in Example 1 where X is 6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O2; Molecular Weight: 405.3; Mass/charge ratio: (100.0%), 404.1 (99.8%), 405.1 (22.7%), 407.1 (22.3%), 408.1 (2.8%); Elemental analysis: C, 59.26; H, 6.22; Br, 19.71; N, 6.91; O, 7.89.
Synthesised according to the procedure disclosed in Example 1 where X is 6-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O2; Molecular Weight: 340.5; Mass/charge ratio: 340.2 (100.0%), 341.2 (23.8%), 342.2 (3.1%); Elemental analysis: C, 74.08; H, 8.29; N, 8.23; O, 9.40.
Synthesised according to the procedure disclosed in Example 1 where X is 7-chloro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23ClN2O; Molecular Weight: 330.9; Mass/charge ratio: 330.1 (100.0%), 332.1 (32.0%), 331.2 (20.9%), 333.2 (6.9%), 332.2 (2.4%); Elemental analysis: C, 68.97; H, 7.01; Cl, 10.72; N, 8.47; O, 4.84.
Synthesised according to the procedure disclosed in Example 1 where X is 7-bromo indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H23BrN2O; Molecular Weight: 375.3; Mass/charge ratio: 374.1 (100.0%), 376.1 (99.7%), 375.1 (21.6%), 377.1 (21.2%), 378.1 (2.4%); Elemental analysis: C, 60.81; H, 6.18; Br, 21.29; N, 7.46; O, 4.26.
Synthesised according to the procedure disclosed in Example 1 where X is 7-methyl indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H26N2O; Molecular Weight: 310.4; Mass/charge ratio: 310.2 (100.0%), 311.2 (22.7%), 312.2 (2.7%); Elemental analysis: C, 77.38; H, 8.44; N, 9.02; O, 5.15.
Synthesised according to the procedure disclosed in Example 1 where X is 7-chloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O; Molecular Weight: 344.9; Mass/charge ratio: 344.2 (100.0%), 346.2 (34.6%), 345.2 (22.7%), 347.2 (7.5%); Elemental analysis: C, 69.65; H, 7.31; Cl, 10.28; N, 8.12; O, 4.64.
Synthesised according to the procedure disclosed in Example 1 where X is 7-bromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O; Molecular Weight: 389.3; Mass/charge ratio: 388.1 (100.0%), 390.1 (99.9%), 389.1 (22.7%), 391.1 (22.3%), 392.1 (2.6%); Elemental analysis: C, 61.70; H, 6.47; Br, 20.52; N, 7.20; O, 4.11.
Synthesised according to the procedure disclosed in Example 1 where X is 7-methyl indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O; Molecular Weight: 324.5; Mass/charge ratio: 324.2 (100.0%), 325.2 (23.8%), 326.2 (2.9%); Elemental analysis: C, 77.74; H, 8.70; N, 8.63; O, 4.93.
Synthesised according to the procedure disclosed in Example 1 where X is 7-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O2; Molecular Weight: 360.9; Mass/charge ratio: 360.2 (100.0%), 362.2 (34.8%), 361.2 (22.7%), 363.2 (7.5%); Elemental analysis: C, 66.56; H, 6.98; Cl, 9.82; N, 7.76; O, 8.87.
Synthesised according to the procedure disclosed in Example 1 where X is 7-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O2; Molecular Weight: 405.3; Mass/charge ratio: 406.1 (100.0%), 404.1 (99.8%), 405.1 (22.7%), 407.1 (22.3%), 408.1 (2.8%); Elemental analysis: C, 59.26; H, 6.22; Br, 19.71; N, 6.91; O, 7.89.
Synthesised according to the procedure disclosed in Example 1 where X is 7-methyl indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H28N2O2; Molecular Weight: 340.5; Mass/charge ratio: 340.2 (100.0%), 341.2 (23.8%), 342.2 (3.1%); Elemental analysis: C, 74.08; H, 8.29; N, 8.23; O, 9.40.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-fluoro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22ClFN2O; Molecular Weight: 336.8; Mass/charge ratio: 336.1 (100.0%), 338.1 (34.1%), 337.1 (20.5%), 339.1 (6.6%); Elemental analysis: C, 64.18; H, 6.58; Cl, 10.53; F, 5.64; N, 8.32; O, 4.75.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-fluoro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22BrFN2O; Molecular Weight: 381.3; Mass/charge ratio: 380.1 (100.0%), 382.1 (99.5%), 381.1 (20.5%), 383.1 (20.1%), 384.1 (2.1%); Elemental analysis: C, 56.70; H, 5.82; Br, 20.96; F, 4.98; N, 7.35; O, 4.20.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-fluoro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25FN2O; Molecular Weight: 316.4; Mass/charge ratio: 316.2 (100.0%), 317.2 (21.6%), 318.2 (2.4%); Elemental analysis: C, 72.12; H, 7.96; F, 6.00; N, 8.85; O, 5.06.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-fluoro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24ClFN2O; Molecular Weight: 350.9; Mass/charge ratio: 350.2 (100.0%), 352.2 (34.4%), 351.2 (21.6%), 353.2 (7.1%); Elemental analysis: C, 65.04; H, 6.89; Cl, 10.10; F, 5.41; N, 7.98; O, 4.56.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-fluoro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24BrFN2O; Molecular Weight: 395.3; Mass/charge ratio: 394.1 (100.0%), 396.1 (99.7%), 395.1 (21.6%), 397.1 (21.2%), 398.1 (2.4%); Elemental analysis: C, 57.73; H, 6.12; Br, 20.21; F, 4.81; N, 7.09; O, 4.05.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-fluoro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H27FN2O; Molecular Weight: 330.4; Mass/charge ratio: 330.2 (100.0%), 331.2 (22.7%), 332.2 (2.7%); Elemental analysis: C, 72.70; H, 8.24; F, 5.75; N, 8.48; O, 4.84.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-fluoro indole, Y is isopropyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H26ClFN2O; Molecular Weight: 364.9; Mass/charge ratio: 364.2 (100.0%), 366.2 (34.6%), 365.2 (22.7%), 367.2 (7.5%); Elemental analysis: C, 65.83; H, 7.18; Cl, 9.72; F, 5.21; N, 7.68; O, 4.38.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-fluoro indole, Y is isopropyl bromide, and Z is cycloheptylmethyl amine. Formula: C20H26BrFN2O; Molecular Weight: 409.3; Mass/charge ratio: 408.1 (100.0%), 410.1 (99.9%), 409.1 (22.7%), 411.1 (22.3%), 412.1 (2.6%); Elemental analysis: C, 58.68; H, 6.40; Br, 19.52; F, 4.64; N, 6.84; O, 3.91.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24ClFN2O2; Molecular Weight: 366.9; Mass/charge ratio: 366.2 (100.0%), 368.1 (32.0%), 367.2 (20.9%), 369.2 (6.9%), 368.2 (2.6%); Elemental analysis: C, 62.20; H, 6.59; Cl, 9.66; F, 5.18; N, 7.64; O, 8.72.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24BrFN2O2; Molecular Weight: 411.3; Mass/charge ratio: 410.1 (100.0%), 412.1 (99.9%), 411.1 (21.6%), 413.1 (21.3%), 414.1 (2.6%); Elemental analysis: C, 55.48; H, 5.88; Br, 19.43; F, 4.62; N, 6.81; O, 7.78.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H27FN2O2; Molecular Weight: 346.4; Mass/charge ratio: 346.2 (100.0%), 347.2 (22.8%), 348.2 (2.9%); Elemental analysis: C, 69.34; H, 7.86; F, 5.48; N, 8.09; O, 9.24.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dichloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22Cl2N2O; Molecular Weight: 353.3; Mass/charge ratio: 352.1 (100.0%), 354.1 (66.1%), 353.1 (20.5%), 355.1 (13.3%), 356.1 (11.6%), 357.1 (2.2%); Elemental analysis: C, 61.19; H, 6.28; Cl, 20.07; N, 7.93; O, 4.53.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-chloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22ClFN2O; Molecular Weight: 336.8; Mass/charge ratio: 336.1 (100.0%), 338.1 (34.1%), 337.1 (20.5%), 339.1 (6.6%); Elemental analysis: C, 64.18; H, 6.58; Cl, 10.53; F, 5.64; N, 8.32; O, 4.75.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-chloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22BrClN2O; Molecular Weight: 397.7; Mass/charge ratio: 398.1 (100.0%), 396.1 (76.1%), 400.1 (25.8%), 399.1 (20.3%), 397.1 (15.6%), 401.1 (5.0%); Elemental analysis: C, 54.36; H, 5.58; Br, 20.09; Cl, 8.91; N, 7.04; O, 4.02.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-chloro indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25ClN2O; Molecular Weight: 332.9; Mass/charge ratio: 332.2 (100.0%), 334.2 (34.4%), 333.2 (21.6%), 335.2 (7.1%); Elemental analysis: C, 68.56; H, 7.57; Cl, 10.65; N, 8.42; O, 4.81.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-chloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24ClFN2O; Molecular Weight: 350.9; Mass/charge ratio: 350.2 (100.0%), 352.2 (34.4%), 351.2 (21.6%), 353.2 (7.1%); Elemental analysis: C, 65.04; H, 6.89; Cl, 10.10; F, 5.41; N, 7.98; O, 4.56.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dichloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24Cl2N2O; Molecular Weight: 367.3; Mass/charge ratio: 366.1 (100.0%), 368.1 (66.3%), 367.1 (21.6%), 369.1 (14.0%), 370.1 (11.8%), 371.1 (2.3%); Elemental analysis: C, 62.13; H, 6.59; Cl, 19.30; N, 7.63; O, 4.36.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-chloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24BrClN2O; Molecular Weight: 411.8; Mass/charge ratio: 412.1 (100.0%), 410.1 (76.0%), 414.1 (26.0%), 413.1 (21.3%), 411.1 (16.4%), 415.1 (5.3%); Elemental analysis: C, 55.42; H, 5.87; Br, 19.41; Cl, 8.61; N, 6.80; O, 3.89.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-chloro indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H27ClN2O; Molecular Weight: 346.9; Mass/charge ratio: 346.2 (100.0%), 348.2 (34.6%), 347.2 (22.7%), 349.2 (7.5%); Elemental analysis: C, 69.25; H, 7.85; Cl, 10.22; N, 8.08; O, 4.61.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24ClFN2O2; Molecular Weight: 366.9; Mass/charge ratio: 366.2 (100.0%), 368.1 (32.0%), 367.2 (20.9%), 369.2 (6.9%), 368.2 (2.6%); Elemental analysis: C, 62.20; H, 6.59; Cl, 9.66; F, 5.18; N, 7.64; O, 8.72.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dichloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24Cl2N2O2; Molecular Weight: 383.3; Mass/charge ratio: 382.1 (100.0%), 384.1 (66.6%), 383.1 (21.6%), 385.1 (14.1%), 386.1 (11.9%), 387.1 (2.4%); Elemental analysis: C, 59.53; H, 6.31; Cl, 18.50; N, 7.31; O, 8.35.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24BrClN2O2; Molecular Weight: 427.8; Mass/charge ratio: 428.1 (100.0%), 426.1 (75.8%), 430.1 (26.2%), 429.1 (21.4%), 427.1 (16.4%), 431.1 (5.3%); Elemental analysis: C, 53.35; H, 5.66; Br, 18.68; Cl, 8.29; N, 6.55; O, 7.48.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H27ClN2O2; Molecular Weight: 362.9; Mass/charge ratio: 362.2 (100.0%), 364.2 (34.8%), 363.2 (22.8%), 365.2 (7.5%); Elemental analysis: C, 66.19; H, 7.50; Cl, 9.77; N, 7.72; O, 8.82.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-bromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22BrClN2O; Molecular Weight: 397.7; Mass/charge ratio: 398.1 (100.0%), 396.1 (76.1%), 400.1 (25.8%), 399.1 (20.3%), 397.1 (15.6%), 401.1 (5.0%); Elemental analysis: C, 54.36; H, 5.58; Br, 20.09; Cl, 8.91; N, 7.04; O, 4.02.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-bromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22BrFN2O; Molecular Weight: 381.3; Mass/charge ratio: 380.1 (100.0%), 382.1 (99.5%), 381.1 (20.5%), 383.1 (20.1%), 384.1 (2.1%); Elemental analysis: C, 56.70; H, 5.82; Br, 20.96; F, 4.98; N, 7.35; O, 4.20.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dibromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C18H22Br2N2O; Molecular Weight: 442.2; Mass/charge ratio: 442.0 (100.0%), 440.0 (50.8%), 444.0 (50.3%), 443.0 (20.4%), 441.0 (10.4%), 445.0 (10.0%), 446.0 (1.1%); Elemental analysis: C, 48.89; H, 5.01; Br, 36.14; N, 6.34; O, 3.62.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-bromo indole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H25BrN2O; Molecular Weight: 377.3; Mass/charge ratio: 376.1 (100.0%), 378.1 (99.7%), 377.1 (21.6%), 379.1 (21.2%), 380.1 (2.4%); Elemental analysis: C, 60.48; H, 6.68; Br, 21.18; N, 7.42; O, 4.24.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-bromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24BrFN2O; Molecular Weight: 395.3; Mass/charge ratio: 394.1 (100.0%), 396.1 (99.7%), 395.1 (21.6%), 397.1 (21.2%), 398.1 (2.4%); Elemental analysis: C, 57.73; H, 6.12; Br, 20.21; F, 4.81; N, 7.09; O, 4.05.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-bromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24BrClN2O; Molecular Weight: 411.8; Mass/charge ratio: 412.1 (100.0%), 410.1 (76.0%), 414.1 (26.0%), 413.1 (21.3%), 411.1 (16.4%), 415.1 (5.3%); Elemental analysis: C, 55.42; H, 5.87; Br, 19.41; Cl, 8.61; N, 6.80; O, 3.89.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dibromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C19H24Br2N2O; Molecular Weight: 456.2; Mass/charge ratio: 456.0 (100.0%), 454.0 (50.8%), 458.0 (50.4%), 457.0 (21.4%), 455.0 (11.0%), 459.0 (10.6%), 460.0 (1.2%); Elemental analysis: C, 50.02; H, 5.30; Br, 35.03; N, 6.14; O, 3.51.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-bromo indole, Y is ethyl iodide, and Z is cycloheptylmethyl amine. Formula: C20H27BrN2O; Molecular Weight: 391.3; Mass/charge ratio: 390.1 (100.0%), 392.1 (99.9%), 391.1 (22.7%), 393.1 (22.3%), 394.1 (2.6%); Elemental analysis: C, 61.38; H, 6.95; Br, 20.42; N, 7.16; O, 4.09.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24BrFN2O2; Molecular Weight: 411.3; Mass/charge ratio: 410.1 (100.0%), 412.1 (99.9%), 411.1 (21.6%), 413.1 (21.3%), 414.1 (2.6%); Elemental analysis: C, 55.48; H, 5.88; Br, 19.43; F, 4.62; N, 6.81; O, 7.78.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24BrClN2O2; Molecular Weight: 427.8; Mass/charge ratio: 428.1 (100.0%), 426.1 (75.8%), 430.1 (26.2%), 429.1 (21.4%), 427.1 (16.4%), 431.1 (5.3%); Elemental analysis: C, 53.35; H, 5.66; Br, 18.68; Cl, 8.29; N, 6.55; O, 7.48.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dibromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C19H24Br2N2O2; Molecular Weight: 472.2; Mass/charge ratio: 472.0 (100.0%), 470.0 (50.7%), 474.0 (50.6%), 473.0 (21.5%), 471.0 (11.0%), 475.0 (10.6%), 476.0 (1.3%); Elemental analysis: C, 48.33; H, 5.12; Br, 33.84; N, 5.93; O, 6.78.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is cycloheptylmethyl amine. Formula: C20H27BrN2O2; Molecular Weight: 407.3; Mass/charge ratio: 408.1 (100.0%), 406.1 (99.8%), 407.1 (22.7%), 409.1 (22.4%), 410.1 (2.8%); Elemental analysis: C, 58.97; H, 6.68; Br, 19.62; N, 6.88; O, 7.86.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-fluoro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22ClFN2O; Molecular Weight: 348.8; Mass/charge ratio: 348.1 (100.0%), 350.1 (34.3%), 349.1 (21.6%), 351.1 (7.0%); Elemental analysis: C, 65.42; H, 6.36; Cl, 10.16; F, 5.45; N, 8.03; O, 4.59.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-fluoro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22BrFN2O; Molecular Weight: 393.3; Mass/charge ratio: 392.1 (100.0%), 394.1 (99.7%), 393.1 (21.6%), 395.1 (21.2%), 396.1 (2.4%); Elemental analysis: C, 58.02; H, 5.64; Br, 20.32; F, 4.83; N, 7.12; O, 4.07.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-fluoro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25FN2O; Molecular Weight: 328.4; Mass/charge ratio: 328.2 (100.0%), 329.2 (22.7%), 330.2 (2.7%); Elemental analysis: C, 73.14; H, 7.67; F, 5.78; N, 8.53; O, 4.87.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-fluoro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24ClFN2O; Molecular Weight: 362.9; Mass/charge ratio: 362.2 (100.0%), 364.2 (34.6%), 363.2 (22.7%), 365.2 (7.5%); Elemental analysis: C, 66.20; H, 6.67; Cl, 9.77; F, 5.24; N, 7.72; O, 4.41.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-fluoro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrFN2O; Molecular Weight: 407.3; Mass/charge ratio: 406.1 (100.0%), 408.1 (99.9%), 407.1 (22.7%), 409.1 (22.3%), 410.1 (2.6%); Elemental analysis: C, 58.97; H, 5.94; Br, 19.62; F, 4.66; N, 6.88; O, 3.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-fluoro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27FN2O; Molecular Weight: 342.5; Mass/charge ratio: 342.2 (100.0%), 343.2 (23.8%), 344.2 (2.9%); Elemental analysis: C, 73.65; H, 7.95; F, 5.55; N, 8.18; O, 4.67.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24ClFN2O2; Molecular Weight: 378.9; Mass/charge ratio: 378.2 (100.0%), 380.1 (32.0%), 379.2 (22.0%), 381.2 (7.3%), 380.2 (2.9%); Elemental analysis: C, 63.40; H, 6.38; Cl, 9.36; F, 5.01; N, 7.39; O, 8.45.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrFN2O2; Molecular Weight: 423.3; Mass/charge ratio: 424.1 (100.0%), 422.1 (99.8%), 423.1 (22.7%), 425.1 (22.3%), 426.1 (2.8%); Elemental analysis: C, 56.75; H, 5.71; Br, 18.88; F, 4.49; N, 6.62; O, 7.56.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-fluoro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27FN2O2; Molecular Weight: 358.4; Mass/charge ratio: 358.2 (100.0%), 359.2 (23.8%), 360.2 (3.1%); Elemental analysis: C, 70.37; H, 7.59; F, 5.30; N, 7.82; O, 8.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dichloro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22Cl2N2O; Molecular Weight: 365.3; Mass/charge ratio: 364.1 (100.0%), 366.1 (66.3%), 365.1 (21.6%), 367.1 (14.0%), 368.1 (11.8%), 369.1 (2.3%); Elemental analysis: C, 62.47; H, 6.07; Cl, 19.41; N, 7.67; O, 4.38.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-chloro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22ClFN2O; Molecular Weight: 348.8; Mass/charge ratio: 348.1 (100.0%), 350.1 (34.3%), 349.1 (21.6%), 351.1 (7.0%); Elemental analysis: C, 65.42; H, 6.36; Cl, 10.16; F, 5.45; N, 8.03; O, 4.59.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-chloro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22BrClN2O; Molecular Weight: 409.7; Mass/charge ratio: 410.1 (100.0%), 408.1 (76.0%), 412.1 (26.0%), 411.1 (21.3%), 409.1 (16.4%), 413.1 (5.3%); Elemental analysis: C, 55.69; H, 5.41; Br, 19.50; Cl, 8.65; N, 6.84; O, 3.90.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-chloro indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25ClN2O; Molecular Weight: 344.9; Mass/charge ratio: 344.2 (100.0%), 346.2 (34.6%), 345.2 (22.7%), 347.2 (7.5%); Elemental analysis: C, 69.65; H, 7.31; Cl, 10.28; N, 8.12; O, 4.64.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-chloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24ClFN2O; Molecular Weight: 362.9; Mass/charge ratio: 362.2 (100.0%), 364.2 (34.6%), 363.2 (22.7%), 365.2 (7.5%); Elemental analysis: C, 66.20; H, 6.67; Cl, 9.77; F, 5.24; N, 7.72; O, 4.41.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dichloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24Cl2N2O; Molecular Weight: 379.3; Mass/charge ratio: 378.1 (100.0%), 380.1 (66.6%), 379.1 (22.7%), 381.1 (14.7%), 382.1 (11.9%), 383.1 (2.5%); Elemental analysis: C, 63.33; H, 6.38; Cl, 18.69; N, 7.39; O, 4.22.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-chloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrClN2O; Molecular Weight: 423.8; Mass/charge ratio: 424.1 (100.0%), 422.1 (75.8%), 426.1 (26.2%), 425.1 (22.4%), 423.1 (17.2%), 427.1 (5.6%); Elemental analysis: C, 56.68; H, 5.71; Br, 18.86; Cl, 8.37; N, 6.61; O, 3.78.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-chloro indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27ClN2O; Molecular Weight: 358.9; Mass/charge ratio: 358.2 (100.0%), 360.2 (34.9%), 359.2 (23.8%), 361.2 (7.9%); Elemental analysis: C, 70.28; H, 7.58; Cl, 9.88; N, 7.81; O, 4.46.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24ClFN2O2; Molecular Weight: 378.9; Mass/charge ratio: 378.2 (100.0%), 380.1 (32.0%), 379.2 (22.0%), 381.2 (7.3%), 380.2 (2.9%); Elemental analysis: C, 63.40; H, 6.38; Cl, 9.36; F, 5.01; N, 7.39; O, 8.45.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dichloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24Cl2N2O2; Molecular Weight: 395.3; Mass/charge ratio: 394.1 (100.0%), 396.1 (66.8%), 395.1 (22.7%), 397.1 (14.8%), 398.1 (12.1%), 399.1 (2.5%); Elemental analysis: C, 60.76; H, 6.12; Cl, 17.94; N, 7.09; O, 8.09.
Synthesised according to the procedure disclosed in Example 1 where X is 4-bromo-6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrClN2O2; Molecular Weight: 439.8; Mass/charge ratio: 440.1 (100.0%), 438.1 (75.7%), 442.1 (26.4%), 441.1 (22.4%), 439.1 (17.2%), 443.1 (5.6%); Elemental analysis: C, 54.62; H, 5.50; Br, 18.17; Cl, 8.06; N, 6.37; O, 7.28.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-chloro indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27ClN2O2; Molecular Weight: 374.9; Mass/charge ratio: 374.2 (100.0%), 376.2 (35.1%), 375.2 (23.8%), 377.2 (7.9%), 378.2 (1.0%); Elemental analysis: C, 67.28; H, 7.26; Cl, 9.46; N, 7.47; O, 8.54.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-bromo indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22BrClN2O; Molecular Weight: 409.7; Mass/charge ratio: 410.1 (100.0%), 408.1 (76.0%), 412.1 (26.0%), 411.1 (21.3%), 409.1 (16.4%), 413.1 (5.3%); Elemental analysis: C, 55.69; H, 5.41; Br, 19.50; Cl, 8.65; N, 6.84; O, 3.90.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-bromo indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22BrFN2O; Molecular Weight: 393.3; Mass/charge ratio: 392.1 (100.0%), 394.1 (99.7%), 393.1 (21.6%), 395.1 (21.2%), 396.1 (2.4%); Elemental analysis: C, 58.02; H, 5.64; Br, 20.32; F, 4.83; N, 7.12; O, 4.07.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dibromo indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C19H22Br2N2O; Molecular Weight: 454.2; Mass/charge ratio: 454.0 (100.0%), 452.0 (50.8%), 456.0 (50.4%), 455.0 (21.4%), 453.0 (11.0%), 457.0 (10.6%), 458.0 (1.2%); Elemental analysis: C, 50.24; H, 4.88; Br, 35.18; N, 6.17; O, 3.52.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-bromo indole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H25BrN2O; Molecular Weight: 389.3; Mass/charge ratio: 388.1 (100.0%), 390.1 (99.9%), 389.1 (22.7%), 391.1 (22.3%), 392.1 (2.6%); Elemental analysis: C, 61.70; H, 6.47; Br, 20.52; N, 7.20; O, 4.11.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-bromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrFN2O; Molecular Weight: 407.3; Mass/charge ratio: 406.1 (100.0%), 408.1 (99.9%), 407.1 (22.7%), 409.1 (22.3%), 410.1 (2.6%); Elemental analysis: C, 58.97; H, 5.94; Br, 19.62; F, 4.66; N, 6.88; O, 3.93.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-bromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrClN2O; Molecular Weight: 423.8; Mass/charge ratio: 424.1 (100.0%), 422.1 (75.8%), 426.1 (26.2%), 425.1 (22.4%), 423.1 (17.2%), 427.1 (5.6%); Elemental analysis: C, 56.68; H, 5.71; Br, 18.86; Cl, 8.37; N, 6.61; O, 3.78.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dibromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24Br2N2O; Molecular Weight: 468.2; Mass/charge ratio: 468.0 (100.0%), (50.7%), 470.0 (50.6%), 469.0 (22.5%), 467.0 (11.5%), 471.0 (11.1%), 472.0 (1.3%); Elemental analysis: C, 51.30; H, 5.17; Br, 34.13; N, 5.98; O, 3.42.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-bromo indole, Y is ethyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27BrN2O; Molecular Weight: 403.4; Mass/charge ratio: 404.1 (100.0%), (99.8%), 403.1 (23.8%), 405.1 (23.4%), 406.1 (2.8%); Elemental analysis: C, 62.53; H, 6.75; Br, 19.81; N, 6.95; O, 3.97.
Synthesised according to the procedure disclosed in Example 1 where X is 4-fluoro-6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrFN2O2; Molecular Weight: 423.3; Mass/charge ratio: 424.1 (100.0%), 422.1 (99.8%), 423.1 (22.7%), 425.1 (22.3%), 426.1 (2.8%); Elemental analysis: C, 56.75; H, 5.71; Br, 18.88; F, 4.49; N, 6.62; O, 7.56.
Synthesised according to the procedure disclosed in Example 1 where X is 4-chloro-6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24BrClN2O2; Molecular Weight: 439.8; Mass/charge ratio: 440.1 (100.0%), 438.1 (75.7%), 442.1 (26.4%), 441.1 (22.4%), 439.1 (17.2%), 443.1 (5.6%); Elemental analysis: C, 54.62; H, 5.50; Br, 18.17; Cl, 8.06; N, 6.37; O, 7.28.
Synthesised according to the procedure disclosed in Example 1 where X is 4,6-dibromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C20H24Br2N2O2; Molecular Weight: 484.2; Mass/charge ratio: 484.0 (100.0%), 486.0 (50.8%), 482.0 (50.7%), 485.0 (22.5%), 483.0 (11.5%), 487.0 (11.2%), 488.0 (1.4%); Elemental analysis: C, 49.61; H, 5.00; Br, 33.00; N, 5.79; O, 6.61.
Synthesised according to the procedure disclosed in Example 1 where X is 4-methyl-6-bromo indole, Y is O-t-butyldimethylsilyl-2-chloroethanol, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H27BrN2O2; Molecular Weight: 419.4; Mass/charge ratio: 420.1 (100.0%), 418.1 (99.6%), 419.1 (23.7%), 421.1 (23.4%), 422.1 (3.1%); Elemental analysis: C, 60.15; H, 6.49; Br, 19.05; N, 6.68; O, 7.63.
Formula: C17H22ClN3O; Molecular Weight: 319.8; Mass/charge ratio: 319.1 (100.0%), (32.4%), 320.1 (19.5%), 322.1 (6.3%), 321.2 (1.6%); Elemental analysis: C, 63.84; H, 6.93; Cl, 11.08; N, 13.14; O, 5.00.
Formula: C17H22BrN3O; Molecular Weight: 364.3; Mass/charge ratio: 363.1 (100.0%), (99.3%), 364.1 (19.8%), 366.1 (19.4%), 367.1 (2.0%); Elemental analysis: C, 56.05; H, 6.09; Br, 21.93; N, 11.54; O, 4.39.
Formula: C18H22ClN3O; Molecular Weight: 331.8; Mass/charge ratio: 331.1 (100.0%), (32.4%), 332.1 (20.6%), 334.1 (6.7%), 333.2 (1.8%); Elemental analysis: C, 65.15; H, 6.68; Cl, 10.68; N, 12.66; O, 4.82.
Formula: C18H22BrN3O; Molecular Weight: 376.3; Mass/charge ratio: 375.1 (100.0%), (99.6%), 376.1 (20.9%), 378.1 (20.5%), 379.1 (2.2%); Elemental analysis: C, 57.45; H, 5.89; Br, 21.23; N, 11.17; O, 4.25.
Synthesised according to the procedure disclosed in Example 2 where X is 4-chloro-7-azaindole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C17H22ClN3O; Molecular Weight: 319.8; Mass/charge ratio: 319.1 (100.0%), 321.1 (32.4%), 320.1 (19.5%), 322.1 (6.3%), 321.2 (1.6%); Elemental analysis: C, 63.84; H, 6.93; Cl, 11.08; N, 13.14; O, 5.00.
Synthesised according to the procedure disclosed in Example 2 where X is 4-bromo-7-azaindole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C17H22BrN3O; Molecular Weight: 364.3; Mass/charge ratio: 363.1 (100.0%), 365.1 (99.3%), 364.1 (19.8%), 366.1 (19.4%), 367.1 (2.0%); Elemental analysis: C, 56.05; H, 6.09; Br, 21.93; N, 11.54; O, 4.39.
Synthesised according to the procedure disclosed in Example 2 where X is 4-chloro-7-azaindole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C18H22ClN3O; Molecular Weight: 331.8; Mass/charge ratio: 331.1 (100.0%), (32.4%), 332.1 (20.6%), 334.1 (6.7%), 333.2 (1.8%); Elemental analysis: C, 65.15; H, 6.68; Cl, 10.68; N, 12.66; O, 4.82.
Synthesised according to the procedure disclosed in Example 2 where X is 4-bromo-7-azaindole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C18H22BrN3O; Molecular Weight: 376.3; Mass/charge ratio: 375.1 (100.0%), (99.6%), 376.1 (20.9%), 378.1 (20.5%), 379.1 (2.2%); Elemental analysis: C, 57.45; H, 5.89; Br, 21.23; N, 11.17; O, 4.25.
Synthesised according to the procedure disclosed in Example 2 where X is 4-chloro-5-azaindole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C17H22ClN3O; Molecular Weight: 319.1 (100.0%), 321.1 (32.4%), 320.1 (19.5%), (6.3%), 321.2 (1.6%); Mass/charge ratio; Elemental analysis: C, 63.84; H, 6.93; Cl, 11.08; N, 13.14; O, 5.00.
Synthesised according to the procedure disclosed in Example 2 where X is 4-bromo-5-azaindole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C17H22BrN3O; Molecular Weight: 364.3; Mass/charge ratio: 363.1 (100.0%), 365.1 (99.3%), 364.1 (19.8%), 366.1 (19.4%), 367.1 (2.0%); Elemental analysis: C, 56.05; H, 6.09; Br, 21.93; N, 11.54; O, 4.39.
Synthesised according to the procedure disclosed in Example 2 where X is 4-chloro-5-azaindole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C18H22ClN3O; Molecular Weight: 331.8; Mass/charge ratio: 331.1 (100.0%), 333.1 (32.4%), 332.1 (20.6%), 334.1 (6.7%), 333.2 (1.8%); Elemental analysis: C, 65.15; H, 6.68; Cl, 10.68; N, 12.66; O, 4.82.
Synthesised according to the procedure disclosed in Example 2 where X is 4-bromo-5-azaindole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C18H22BrN3O; Molecular Weight: 376.3; Mass/charge ratio: 375.1 (100.0%), (99.6%), 376.1 (20.9%), 378.1 (20.5%), 379.1 (2.2%); Elemental analysis: C, 57.45; H, 5.89; Br, 21.23; N, 11.17; O, 4.25.
Synthesised according to the procedure disclosed in Example 2 where X is 4-chloro-6-azaindole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C17H22ClN3O; Molecular Weight: 319.8; Mass/charge ratio: 319.1 (100.0%), 321.1 (32.4%), 320.1 (19.5%), 322.1 (6.3%), 321.2 (1.6%); Elemental analysis: C, 63.84; H, 6.93; Cl, 11.08; N, 13.14; O, 5.00.
Synthesised according to the procedure disclosed in Example 2 where X is 4-bromo-6-azaindole, Y is methyl iodide, and Z is cycloheptylmethyl amine. Formula: C17H22BrN3O; Molecular Weight: 364.3; Mass/charge ratio: 363.1 (100.0%), 365.1 (99.3%), 364.1 (19.8%), 366.1 (19.4%), 367.1 (2.0%); Elemental analysis: C, 56.05; H, 6.09; Br, 21.93; N, 11.54; O, 4.39.
Synthesised according to the procedure disclosed in Example 2 where X is 4-chloro-6-azaindole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C18H22ClN3O; Molecular Weight: 331.8; Mass/charge ratio: 331.1 (100.0%), 333.1 (32.4%), 332.1 (20.6%), 334.1 (6.7%), 333.2 (1.8%); Elemental analysis: C, 65.15; H, 6.68; Cl, 10.68; N, 12.66; O, 4.82.
Synthesised according to the procedure disclosed in Example 2 where X is 4-bromo-6-azaindole, Y is methyl iodide, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C18H22BrN3O; Molecular Weight: 376.3; Mass/charge ratio: 375.1 (100.0%), (99.6%), 376.1 (20.9%), 378.1 (20.5%), 379.1 (2.2%); Elemental analysis: C, 57.45; H, 5.89; Br, 21.23; N, 11.17; O, 4.25.
General procedure for preparation of XInt01: A solution of the indole derivative X (1 eq) in dry dimethylformamide at 0° C. was added to trifluoroacetic anhydride (1.5 eq), stirred, and slowly warmed to room temperature. After completion of the reaction (1 h), the mixture was treated with ice-cold water to obtain a solid. The solid was separated by filtration and washed with water and n-pentane and dried under high vacuum to afford compound XInt01 (80-94% yield).
General procedure for preparation of XZInt02: To a mixture of XInt01 (1 eq) and a cycloalkyl amine Z (1.5 eq) like cyclopentylmethyl amine, cyclopentylethyl amine, cyclohexylmethyl amine, clyclohexylethyl amine, cycloheptylmethyl amine, cycloheptylethyl amine, bicyclo[2.2.2]octan-1-ylmethyl amine) prepared according to the procedures disclosed in Unig and Kahanek (1957) Chem Ber 90:236, Delany and Berchtold (1988) J Org Chem 53:3262-3265, Grob et al. (1958) Helv Chim Acta 41:1191-1197, Whitney et al. (1970) J Med Chem 13:254-260), or bicyclo[2.2.2]octan-1-ylethyl amine, in dry THF at −78° C. was added lithium hexamethyldisilazide (3.5 eq). The resulting solution was warmed to room temperature and subsequently heated to reflux for 3 hours. Ice-cold water was then added to the reaction mixture and extracted 3 times with EtOAc. The combined organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure. The residue obtained was purified by flash chromatography (SiO2, 100-200 mesh) to afford XZInt02 as a solid.
General procedure for preparation of XZInt03: To a solution of XZInt02 in dimethylformamide, were added 3-bromopropionitrile and K2CO3 and the resultant reaction mixture was heated to 60° C. After 16 hours, the reaction mixture was diluted with ice water and extracted 3 times with EtOAc. The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford XZInt03 as a solid.
General procedure for preparation of XZ: To a solution of XZInt03 in dimethylformamide were added NH4Cl and NaN3 and the resultant reaction mixture was heated to 125° C. After 8 hours, the reaction mixture was diluted with ice water and extracted 3 times with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (SiO2, 100-200 mesh, 4% MeOH in DCM) afforded XZ as a solid.
Synthesised according to the procedure disclosed in Example 276 where X is 4-chloro indole, and Z is cycloheptylmethyl amine. Formula: C20H25ClN6O; Molecular Weight: 400.9; Mass/charge ratio: 400.2 (100.0%), 402.2 (35.0%), 401.2 (24.2%), 403.2 (8.0%); Elemental analysis: C, 59.92; H, 6.29; Cl, 8.84; N, 20.96; O, 3.99.
Synthesised according to the procedure disclosed in Example 276 where X is 4-bromo indole, and Z is cycloheptylmethyl amine. Formula: C20H25BrN6O; Molecular Weight: 445.4; Mass/charge ratio: 446.1 (100.0%), 444.1 (99.7%), 445.1 (24.1%), (23.7%), 448.1 (2.9%); Elemental analysis: C, 53.94; H, 5.66; Br, 17.94; N, 18.87; O, 3.59.
Synthesised according to the procedure disclosed in Example 276 where X is 4-methyl indole, and Z is cycloheptylmethyl amine. Formula: C21H28N6O; Molecular Weight: 380.5; Mass/charge ratio: 380.2 (100.0%), 381.2 (25.3%), 382.2 (3.3%); Elemental analysis: C, 66.29; H, 7.42; N, 22.09; O, 4.20.
Synthesised according to the procedure disclosed in Example 276 where X is 4-chloro indole, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H25ClN6O; Molecular Weight: 412.9; Mass/charge ratio: 412.2 (100.0%), 414.2 (35.2%), 413.2 (25.3%), 415.2 (8.4%), 416.2 (1.1%); Elemental analysis: C, 61.08; H, 6.10; Cl, 8.59; N, 20.35; O, 3.87.
Synthesised according to the procedure disclosed in Example 276 where X is 4-bromo indole, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C21H25BrN6O; Molecular Weight: 457.4; Mass/charge ratio: 458.1 (100.0%), 456.1 (99.5%), 457.1 (25.1%), 459.1 (24.7%), 460.1 (3.2%); Elemental analysis: C, 55.15; H, 5.51; Br, 17.47; N, 18.37; O, 3.50.
Synthesised according to the procedure disclosed in Example 276 where X is 4-methyl indole, and Z is bicyclo[2.2.2]octan-1-ylmethyl amine. Formula: C22H28N6O; Molecular Weight: 392.5; Mass/charge ratio: 392.2 (100.0%), 393.2 (26.4%), 394.2 (3.5%); Elemental analysis: C, 67.32; H, 7.19; N, 21.41; O, 4.08.
General procedure for preparation of XInt01: A solution of the indole derivative X (1 eq) in dry dimethylformamide at 0° C. was added to trifluoroacetic anhydride (1.5 eq), stirred, and slowly warmed to room temperature. After completion of the reaction (1 h), the mixture was treated with ice-cold water to obtain a solid. The solid was separated by filtration and washed with water and n-pentane and dried under high vacuum to afford compound XInt01 (80-94% yield).
General procedure for preparation of XZInt02: To a mixture of XInt01 (1 eq) and a cycloalkyl amine Z (1.5 eq) like cyclopentylmethyl amine, cyclopentylethyl amine, cyclohexylmethyl amine, clyclohexylethyl amine, cycloheptylmethyl amine, cycloheptylethyl amine, bicyclo[2.2.2]octan-1-ylmethyl amine (prepared according to the procedures disclosed in Unig and Kahanek (1957) Chem Ber 90:236, Delany and Berchtold (1988) J Org Chem 53:3262-3265, Grob et al. (1958) Helv Chim Acta 41:1191-1197, Whitney et al. (1970) J Med Chem 13:254-260.), or bicyclo[2.2.2]octan-1-ylethyl amine, in dry THF at −78° C. was added lithium hexamethyldisilazide (3.5 eq). The resulting solution was warmed to room temperature and subsequently heated to reflux for 3 hours. Ice-cold water was then added to the reaction mixture and extracted 3 times with EtOAc. The combined organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure. The residue obtained was purified by flash chromatography (SiO2, 100-200 mesh) to afford XZInt02 as a solid.
General Procedure for Preparation of XZInt03:
To a solution of XZInt02 in THF at 0-5° C. were added Et3N and phenyl chloroformate (ClCOOPh). The resultant reaction mixture was slowly warmed to room temperature and stirred further. After 2 hours, the reaction mixture was concentrated under reduced pressure. The residue obtained was diluted with water and extracted 3 times with EtOAc. The combined EtOAc layer was washed with brine and dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the title XZInt03 as a solid.
General Procedure for Preparation of XZNR1R2
To solution of XZInt03, Et3N, and methylamine hydrochloride, dimethylamine hydrochloride, or N-ethyl methylamine in DMSO was stirred at room temperature for 16 hours. After completion of reaction (TLC), the reaction mixture was diluted with ice water and 3 times with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography afforded the title compound XZNR1R2 as a solid.
Synthesised according to the procedure disclosed in Example 283 where X is 4-chloro indole, Z is cycloheptylmethyl amine, and methylamine hydrochloride was used. Formula: C19H24ClN3O2; Molecular Weight: 361.9; Mass/charge ratio: 361.2 (100.0%), 363.2 (34.7%), 362.2 (22.0%), 364.2 (6.9%); Elemental analysis: C, 63.06; H, 6.68; Cl, 9.80; N, 11.61; O, 8.84.
Synthesised according to the procedure disclosed in Example 283 where X is 4-bromo indole, Z is cycloheptylmethyl amine, and methylamine hydrochloride was used. Formula: C19H24BrN3O2; Molecular Weight: 406.3; Mass/charge ratio: 405.1 (100.0%), 407.1 (100.0%), 406.1 (22.0%), 408.1 (21.7%), 409.1 (2.7%); Elemental analysis: C, 56.16; H, 5.95; Br, 19.67; N, 10.34; O, 7.88.
Synthesised according to the procedure disclosed in Example 283 where X is 4-chloro indole, Z is bicyclo[2.2.2]octan-1-ylmethyl amine, and methylamine hydrochloride was used. Formula: C20H24ClN3O2; Molecular Weight: 373.9; Mass/charge ratio: 373.2 (100.0%), 375.2 (34.9%), 374.2 (23.1%), 376.2 (7.3%); Elemental analysis: C, 64.25; H, 6.47; Cl, 9.48; N, 11.24; O, 8.56.
Synthesised according to the procedure disclosed in Example 283 where X is 4-bromo indole, Z is bicyclo[2.2.2]octan-1-ylmethyl amine, and methylamine hydrochloride was used. Formula: C20H24BrN3O2; Molecular Weight: 418.3; Mass/charge ratio: 419.1 (100.0%), 417.1 (99.8%), 418.1 (23.0%), 420.1 (22.7%), (2.9%); Elemental analysis: C, 57.42; H, 5.78; Br, 19.10; N, 10.04; O, 7.65.
Synthesised according to the procedure disclosed in Example 283 where X is 4-chloro indole, Z is cycloheptylmethyl amine, and dimethylamine hydrochloride was used. Formula: C20H26ClN3O2; Molecular Weight: 375.9; Mass/charge ratio: 375.2 (100.0%), 377.2 (34.9%), 376.2 (23.1%), 378.2 (7.7%); Elemental analysis: C, 63.91; H, 6.97; Cl, 9.43; N, 11.18; O, 8.51.
Synthesised according to the procedure disclosed in Example 283 where X is 4-bromo indole, Z is cycloheptylmethyl amine, and dimethylamine hydrochloride was used. Formula: C20H26BrN3O2; Molecular Weight: 420.3; Mass/charge ratio: 421.1 (100.0%), 419.1 (99.8%), 420.1 (23.1%), 422.1 (22.7%), 423.1 (2.9%); Elemental analysis: C, 57.15; H, 6.23; Br, 19.01; N, 10.00; O, 7.61.
Synthesised according to the procedure disclosed in Example 283 where X is 4-chloro indole, Z is bicyclo[2.2.2]octan-1-ylmethyl amine, and dimethylamine hydrochloride was used. Formula: C21H26ClN3O2; Molecular Weight: 387.9; Mass/charge ratio: 387.2 (100.0%), 389.2 (35.2%), 388.2 (24.2%), 390.2 (8.0%), 391.2 (1.0%); Elemental analysis: C, 65.02; H, 6.76; Cl, 9.14; N, 10.83; O, 8.25.
Synthesised according to the procedure disclosed in Example 283 where X is 4-bromo indole, Z is bicyclo[2.2.2]octan-1-ylmethyl amine, and dimethylamine hydrochloride was used.
Formula: C21H26BrN3O2; Molecular Weight: 432.4; Mass/charge ratio: 433.1 (100.0%), (99.5%), 432.1 (24.1%), 434.1 (23.7%), 435.1 (3.1%); Elemental analysis: C, 58.34; H, 6.06; Br, 18.48; N, 9.72; O, 7.40.
Synthesised according to the procedure disclosed in Example 283 where X is 4-chloro indole, Z is cycloheptylmethyl amine, and N-ethyl methylamine was used. Formula: C21H28ClN3O2; Molecular Weight: 389.9; Mass/charge ratio: 389.2 (100.0%), (35.2%), 390.2 (24.2%), 392.2 (8.0%), 393.2 (1.1%); Elemental analysis: C, 64.69; H, 7.24; Cl, 9.09; N, 10.78; O, 8.21.
Synthesised according to the procedure disclosed in Example 283 where X is 4-bromo indole, Z is cycloheptylmethyl amine, and N-ethyl methylamine was used. Formula: C21H28BrN3O2; Molecular Weight: 434.4; Mass/charge ratio: 435.1 (100.0%), (99.5%), 434.1 (24.1%), 436.1 (23.7%), 437.1 (3.1%); Elemental analysis: C, 58.07; H, 6.50; Br, 18.40; N, 9.67; O, 7.37.
Synthesised according to the procedure disclosed in Example 283 where X is 4-chloro indole, Z is bicyclo[2.2.2]octan-1-ylmethyl amine, and N-ethyl methylamine was used. Formula: C22H28ClN3O2; Molecular Weight: 401.9; Mass/charge ratio: 401.2 (100.0%), 403.2 (35.4%), 402.2 (25.3%), 404.2 (8.4%), 405.2 (1.1%); Elemental analysis: C, 65.74; H, 7.02; Cl, 8.82; N, 10.45; O, 7.96.
Synthesised according to the procedure disclosed in Example 283 where X is 4-bromo indole, Z is bicyclo[2.2.2]octan-1-ylmethyl amine, and N-ethyl methylamine was used. Formula: C22H28BrN3O2; Molecular Weight: 446.4; Mass/charge ratio: (100.0%), 445.1 (99.2%), 446.1 (25.1%), 448.1 (24.8%), 449.1 (3.4%); Elemental analysis: C, 59.20; H, 6.32; Br, 17.90; N, 9.41; O, 7.17.
| Number | Date | Country | Kind |
|---|---|---|---|
| 08005532 | Mar 2008 | EP | regional |
| Number | Name | Date | Kind |
|---|---|---|---|
| 3705175 | Magdanyi | Dec 1972 | A |
| 7402602 | Bigg et al. | Jul 2008 | B2 |
| 7919503 | Boes | Apr 2011 | B2 |
| Number | Date | Country |
|---|---|---|
| 9929660 | Jun 1999 | WO |
| 0158869 | Aug 2001 | WO |
| 2004074275 | Sep 2004 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 20090312366 A1 | Dec 2009 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61041050 | Mar 2008 | US |
