Substituted pyridine compounds and methods of use

Abstract

Selected novel substituted pyridine compounds are effective for prophylaxis and treatment of diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Description

BACKGROUND OF THE INVENTION

The present invention comprises a new class of compounds useful in treating diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases and other maladies, such as pain, cancer, and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions involving inflammation. This invention also relates to intermediates and processes useful in the preparation of such compounds.

Interleukin-1 (IL-1) and Tumor Necrosis Factor α (TNF-α) are pro-inflammatory cytokines secreted by a variety of cells, including monocytes and macrophages, in response to many inflammatory stimuli (e.g., lipopolysaccharide—LPS) or external cellular stress (e.g., osmotic shock and peroxide).

Elevated levels of TNF-α and/or IL-1 over basal levels have been implicated in mediating or exacerbating a number of disease states including rheumatoid arthritis; Pagets disease; osteophorosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; pancreatic β cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; asthma; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption diseases; graft vs. host reaction; ischemia reperfusion injury; atherosclerosis; brain trauma; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection. HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses (including HSV-1, HSV-2), and herpes zoster are also exacerbated by TNF-α.

It has been reported that TNF-α plays a role in head trauma, stroke, and ischemia. For instance, in animal models of head trauma (rat), TNF-α levels increased in the contused hemisphere (Shohami et al., J. Cereb. Blood Flow Metab. 14, 615 (1994)). In a rat model of ischemia wherein the middle cerebral artery was occluded, the levels of TNF-α mRNA of TNF-α increased (Feurstein et al., Neurosci. Lett. 164, 125 (1993)). Administration of TNF-α into the rat cortex has been reported to result in significant neutrophil accumulation in capillaries and adherence in small blood vessels. TNF-α promotes the infiltration of other cytokines (IL-1β, IL-6) and also chemokines, which promote neutrophil infiltration into the infarct area (Feurstein, Stroke 25, 1481 (1994)). TNF-α has also been implicated to play a role in type II diabetes (Endocrinol. 130, 43-52, 1992; and Endocrinol. 136, 1474-1481, 1995).

TNF-α appears to play a role in promoting certain viral life cycles and disease states associated with them. For instance, TNF-α secreted by monocytes induced elevated levels of HIV expression in a chronically infected T cell clone (Clouse et al., J. Immunol. 142, 431 (1989)). Lahdevirta et al. ( Am. J. Med. 85, 289 (1988)) discussed the role of TNF-α in the HIV associated states of cachexia and muscle degradation.

TNF-α is upstream in the cytokine cascade of inflammation. As a result, elevated levels of TNF-α may lead to elevated levels of other inflammatory and proinflammatory cytokines, such as IL-1, IL-6, and IL-8.

Elevated levels of IL-1 over basal levels have been implicated in mediating or exacerbating a number of disease states including rheumatoid arthritis; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; ulcerative colitis; anaphylaxis; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption diseases; ischemia reperfusion injury; atherosclerosis; brain trauma; multiple sclerosis; sepsis; septic shock; and toxic shock syndrome. Viruses sensitive to TNF-α inhibition, e.g., HIV-1, HIV-2, HIV-3, are also affected by IL-1.

TNF-α and IL-1 appear to play a role in pancreatic β cell destruction and diabetes. Pancreatic β cells produce insulin which helps mediate blood glucose homeostasis. Deterioration of pancreatic β cells often accompanies type I diabetes. Pancreatic β cell functional abnormalities may occur in patients with type II diabetes. Type II diabetes is characterized by a functional resistance to insulin. Further, type II diabetes is also often accompanied by elevated levels of plasma glucagon and increased rates of hepatic glucose production. Glucagon is a regulatory hormone that attenuates liver gluconeogenesis inhibition by insulin. Glucagon receptors have been found in the liver, kidney and adipose tissue. Thus glucagon antagonists are useful for attenuating plasma glucose levels (WO 97/16442, incorporated herein by reference in its entirety). By antagonizing the glucagon receptors, it is thought that insulin responsiveness in the liver will improve, thereby decreasing gluconeogenesis and lowering the rate of hepatic glucose production.

In rheumatoid arthritis models in animals, multiple intra-articular injections of IL-1 have led to an acute and destructive form of arthritis (Chandrasekhar et al., Clinical Immunol Immunopathol. 55, 382 (1990)). In studies using cultured rheumatoid synovial cells, IL-1 is a more potent inducer of stromelysin than is TNF-α (Firestein, Am. J. Pathol. 140, 1309 (1992)). At sites of local injection, neutrophil, lymphocyte, and monocyte emigration has been observed. The emigration is attributed to the induction of chemokines (e.g., IL-8), and the up-regulation of adhesion molecules (Dinarello, Eur. Cytokine Netw. 5, 517-531 (1994)).

IL-1 also appears to play a role in promoting certain viral life cycles. For example, cytokine-induced increase of HIV expression in a chronically infected macrophage line has been associated with a concomitant and selective increase in IL-1 production (Folks et al., J. Immunol. 136, 40 (1986)). Beutler et al. ( J. Immunol. 135, 3969 (1985)) discussed the role of IL-1 in cachexia. Baracos et al. ( New Eng. J. Med. 308, 553 (1983)) discussed the role of IL-1 in muscle degeneration.

In rheumatoid arthritis, both IL-1 and TNF-α induce synoviocytes and chondrocytes to produce collagenase and neutral proteases, which leads to tissue destruction within the arthritic joints. In a model of arthritis (collagen-induced arthritis (CIA) in rats and mice), intra-articular administration of TNF-α either prior to or after the induction of CIA led to an accelerated onset of arthritis and a more severe course of the disease (Brahn et al., Lymphokine Cytokine Res. 11, 253 (1992); and Cooper, Clin. Exp. Immunol. 898, 244 (1992)).

IL-8 has been implicated in exacerbating and/or causing many disease states in which massive neutrophil infiltration into sites of inflammation or injury (e.g., ischemia) is mediated by the chemotactic nature of IL-8, including, but not limited to, the following: asthma, inflammatory bowel disease, psoriasis, adult respiratory distress syndrome, cardiac and renal reperfusion injury, thrombosis and glomerulonephritis. In addition to the chemotaxis effect on neutrophils, IL-8 also has the ability to activate neutrophils. Thus, reduction in IL-8 levels may lead to diminished neutrophil infiltration.

Several approaches have been taken to block the effect of TNF-α. One approach involves using soluble receptors for TNF-α (e.g., TNFR-55 or TNFR-75), which have demonstrated efficacy in animal models of TNF-α-mediated disease states. A second approach to neutralizing TNF-α using a monoclonal antibody specific to TNF-α, cA2, has demonstrated improvement in swollen joint count in a Phase II human trial of rheumatoid arthritis (Feldmann et al., Immunological Reviews, pp. 195-223 (1995)). These approaches block the effects of TNF-α and IL-1 by either protein sequestration or receptor antagonism.

The present invention also relates to a method of treating cancer which is mediated by Raf and Raf-inducable proteins. Raf proteins are kinases activated in response to extracellular mitogenic stimuli such as PDGF, EGF, acidic FGF, thrombin, insulin or endothelin, and also in response to oncoproteins such as v-src, v-sis, and v-fms. Raf functions downstream of ras in signal transduction from the cellular membrane to the nucleus. Compounds in the present invention may be oncolytics through the antagonism of Raf kinase. Antisense constructs which reduce cellular levels of c-Raf and hence Raf activity inhibit the growth of rodent fibroblasts in soft agar, while exhibiting little or no general cytotoxicity. This inhibition of growth in soft agar is highly predictive of tumor responsiveness in whole animals. Moreover Raf antisense constructs have shown efficacy in reducing tumor burden in animals. Examples of cancers where Raf kinase is implicated by overexpression include cancers of the brain, larynx, lung, lymphatic system, urinary tract and stomach, including hystocytic lymphoma, lung adenocarcinoma and small cell lung cancers. Other examples include cancers involving overexpression of upstream activators of Raf or Raf-activating oncogenes, including pancreatic and breast carcinoma.

Substituted imidazole and pyrrole compounds have been described for use in the treatment of cytokine mediated diseases by inhibition of proinflammatory cytokines, such as IL-1, IL-6, IL-8 and TNF. Substituted imidazoles for use in the treatment of cytokine mediated diseases have been described in U.S. Pat. No. 5,593,992; WO 93/14081; WO 96/18626; WO 96/21452; WO 96/21654; WO 96/40143; WO 97/05878; WO 97/05878; (each of which is incorporated herein by reference in its entirety). Substituted imidazoles for use in the treatment of inflammation has been described in U.S. Pat. No. 3,929,807 (which is incorporated herein by reference in its entirety). Substituted pyrrole compounds for use in the treatment of cytokine mediated diseases have been described in WO 97/05877; WO 97/05878; WO 97/16426; WO 97/16441; and WO 97/16442 (each of which is incorporated herein by reference in its entirety).

Substituted 2-aminopyridine compounds have been described as nitric oxide synthase inhibitors for use in the treatment of inflammation, neurodegenerative disorders and disorders of gastrointestinal motility in WO 96/18616 and WO 96/18617.

Diaryl substituted pyridine compounds have been described for use in the treatment of inflammation and inflammation related disorders in WO 96/24584 and U.S. Pat. No. 5,596,008.

U.S. Pat. No. 3,980,652, U.S. Pat. No. 3,991,057 and U.S. Pat. No. 4,002,629 describe piperazinyl substituted pyridine compounds for use as anti-inflammatory and cardiovascular agents.

JP 6135934 describes substituted pyridine compounds as phospholipase A2 inhibitors for use as antiphlogistic and anti-pancreatitis agents. GB 1,189,188 describes pyrimidin-2-ylamino substituted pyridine compounds as therapeutically valuable compounds for use as antiphlogistic agents.

BRIEF DESCRIPTION OF THE INVENTION

The present invention comprises a new class of compounds useful in the prophylaxis and treatment of disease, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases and other maladies, such as pain, cancer, and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions involving inflammation. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds, methods for the prophylaxis and treatment of TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, such as inflammatory, pain and diabetes diseases, using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of the compounds of the invention.

The compounds of the invention are represented by the following general structure:

wherein R 1 , R 5 , R 6 , R 7 , X and Y are defined below.

The foregoing merely summarizes certain aspects of the invention and is not intended, nor should it be construed, as limiting the invention in any way. All patents and other publications recited herein are hereby incorporated by reference in their entirety.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, there is provided compounds of the formula:

or a pharmaceutically acceptable salt thereof, wherein

X is O, S, S(O), S(O) 2 or NR 2 ; preferably, X is O, S or NR 2 ; more preferably, X is O or NR 2 ; most preferably, X is NR 2 ;

Y is —C(O)—NR 3 R 4 or —NR 4 —C(O)—R 3 ;

R 1 is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R 18 —Z 18 - or R 18 —Z 18 -alkyl;

preferably, R 1 is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C 1 -C 6 alkyl, halo, C 1 -C 6 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R 18 —Z 18 - or R 18 —Z 18 -C 1 -C 6 alkyl;

more preferably, R 1 is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R 18 —Z 18 - or R 18 —Z 18 -C 1 -C 4 alkyl;

provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R 1 is 1-3, preferably, 1-2, and provided when Y is —NR 4 —C(O)—R 3 and X is O or S, R 1 is other than a 2-pyrimidinyl radical;

more preferably, R 1 is a radical of the formula

wherein

R 22 , R 23 , R 24 , R 25 and R 26 are each independently a radical of hydrogen, C 1 -C 4 alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino, R 18 —Z 18 - or R 18 —Z 18 -C 1 -C 4 alkyl; provided at least one of R 21 , R 22 , R 23 , R 24 and R 25 is hydrogen; and provided that the combined total number of aryl and heteroaryl radicals in R 22 , R 23 , R 24 , R 25 and R 26 is 0-1;

R 2 is a hydrogen or alkyl radical; preferably, R 2 is a hydrogen or C 1 -C 4 alkyl radical; more preferably, R 2 is a hydrogen or C 1 -C 2 alkyl radical; more preferably, R 2 is a hydrogen or methyl radical; and most preferably, R 2 is a hydrogen radical;

R 3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R 19 —Z 19 - or R 19 —Z 19 -alkyl; preferably, R 3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C 1 -C 6 alkyl, halo, C 1 -C 6 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R 19 —Z 19 - or R 19 —Z 19 -C 1 -C 6 alkyl; more preferably, R 3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C 1 -C 6 alkyl, halo, C 1 -C 4 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R 19 —Z 19 - or R 19 —Z 19 -C 1 -C 4 alkyl;

provided that the total number of aryl and heteroaryl radicals in R 3 is 1-3, preferably, 1-2; and provided when Y is —C(O)—NR 3 R 4 , R 3 is other than a phenyl or naphthyl having an amino, nitro, cyano, carboxy or alkoxycarbonyl substituent bonded to the ring carbon atom adjacent to the ring carbon atom bonded to —NR 4 —;

more preferably, R 3 is a radical of the formula

wherein

U is C—R 13 or N;

V and W are each independently C—R 12 or N;

R 11 and R 13 are each independently a radical of hydrogen, C 1 -C 4 alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R 19 —Z 19 —; preferably R 11 and R 13 are each independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, cyano, azido, nitro, amidino, R 19 —O—, R 19 —S(O) 2 —, R 19 —O—C(O)—, R 19 —C(O)—, R 19 —NR 21 —C(O)— or R 19 —NR 21 —S(O) 2 —;

each R 12 is independently a radical of hydrogen, C 1 -C 6 alkyl, halo, C 1 -C 4 haloalkyl of 1-3 halo radicals, R 31 —Z 31 - or R 31 —Z 31 -C 1 -C 4 alkyl; preferably, each R 12 is independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, trifluoromethoxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, aminomethyl, (methylamino)methyl or (dimethylamino)methyl;

provided that the combined total number of aryl and heteroaryl radicals in R 11 , R 12 and R 13 is 0-1;

wherein each R 31 is independently a hydrogen, C 1 -C 4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C 1 -C 4 alkyl or heteroaryl-C 1 -C 4 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

each Z 31 is independently —O—, —NR 21 —, —NR 21 —C(O)—, —C(O)—NR 21 —, —NR 21 —S(O) 2 — or —S(O) 2 —NR 21 —;

R 4 is a hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl or R 20 —Z 20 -alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, R 4 is a radical of hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 haloalkyl of 1-3 halo radicals, C 2 -C 6 haloalkenyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C 1 -C 4 alkyl, heteroaryl-C 1 -C 4 alkyl or R 20 —Z 20 -C 1 -C 6 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, C 1 -C 5 alkanoylamino, C 1 -C 4 alkylsulfonylamino, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, (C 1 -C 4 alkoxy)carbonylamino, (C 1 -C 4 alkoxy)carbonyl, cyano, halo, azido, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl of 1-3 halo radicals or C 1 -C 4 haloalkoxy of 1-3 halo radicals;

more preferably, R 4 is a radical of hydrogen, C 1 -C 6 alkyl, aryl, heteroaryl, aryl-C 1 -C 4 alkyl, heteroaryl-C 1 -C 4 alkyl or R 20 —Z 20 -C 2 -C 4 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, acetylamino, halo, C 1 -C 4 alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, R 4 is a radical of hydrogen, C 1 -C 6 alkyl, aryl, heteroaryl, aryl-C 1 -C 4 alkyl, heteroaryl-C 1 -C 4 alkyl or R 20 —Z 20 -C 2 -C 4 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

more preferably, R 4 is a radical of hydrogen, methyl or ethyl radical;

wherein each R 18 is independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, each R 18 is independently a hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl 1-3 halo radicals, aryl, heteroaryl, aryl-C 1 -C 4 alkyl or heteroaryl-C 1 -C 4 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, C 1 -C 5 alkanoylamino, C 1 -C 4 alkylsulfonylamino, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, (C 1 -C 4 alkoxy)carbonylamino, (C 1 -C 4 alkoxy)carbonyl, cyano, halo, azido, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl of 1-3 halo radicals or C 1 -C 4 haloalkoxy of 1-3 halo radicals;

more preferably, each R 18 is independently a hydrogen, C 1 -C 4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C 1 -C 2 alkyl or heteroaryl-C 1 -C 2 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, acetylamino, cyano, halo, azido, C 1 -C 4 alkyl, trifluoromethyl or trifluoromethoxy;

each Z 18 is independently —O—, —S—, —S(O)—, —S(O) 2 —, —CO 2 —, —C(O)—, —NR 21 —, —NR 21 —C(O)—, —C(O)—NR 21 —, —NR 21 —S(O) 2 — or —S(O) 2 —NR 21 —; preferably, each Z 18 is independently —O—, —S—, —S(O) 2 —, —CO 2 —, —NR 21 —, —NR 21 —C(O)—, —C(O)—NR 21 —, —NR 21 —S(O) 2 — or —S(O) 2 —NR 21 —;

wherein each R 19 is independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, each R 19 is independently a hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C 1 -C 4 alkyl or heteroaryl-C 1 -C 4 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, C 1 -C 5 alkanoylamino, C 1 -C 4 alkylsulfonylamino, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, (C 1 -C 4 alkoxy)carbonylamino, (C 1 -C 4 alkoxy)carbonyl, cyano, halo, azido, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl of 1-3 halo radicals or C 1 -C 4 haloalkoxy of 1-3 halo radicals;

more preferably, each R 19 is independently a hydrogen, C 1 -C 4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C 1 -C 4 alkyl or heteroaryl-C 1 -C 4 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, acetylamino, cyano, halo, C 1 -C 4 alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R 19 is independently a hydrogen, C 1 -C 4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C 1 -C 4 alkyl or heteroaryl-C 1 -C 4 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R 19 is independently a hydrogen, methyl, ethyl, trifluoromethyl, phenyl, heteroaryl, phenylmethyl or heteroaryl-methyl radical, wherein the phenyl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, fluoro, chloro, methyl, ethyl, trifluorometyl or trifluoromethoxy;

each Z 19 is independently —O—, —S—, —S(O)—, —S(O) 2 —, —CO 2 —, —C(O)—, —NR 21 —, —NR 21 —C(O)—, —C(O)—NR 21 —, —NR 21 —S(O) 2 — or —S(O) 2 —NR 21 —; preferably, each Z 19 is independently —O—, —S(O) 2 —, —CO 2 —, —C(O)—, —NR 21 —C(O)—, —C(O)—NR 21 —, —NR 21 —S(O) 2 — or —S(O) 2 —NR 21 —; more preferably, each Z 19 is independently —O—, —S(O) 2 —, —O—C(O)—, —C(O)—, —NR 21 —C(O)— or —NR 21 —S(O) 2 —;

wherein each R 20 is independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthio, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;

preferably, each R 20 is independently a hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C 1 -C 4 alkyl or heteroaryl-C 1 -C 4 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, C 1 -C 5 alkanoylamino, C 1 -C 4 alkylsulfonylamino, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, (C 1 -C 4 alkoxy)carbonylamino, (C 1 -C 4 alkoxy)carbonyl, cyano, halo, azido, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl of 1-3 halo radicals or C 1 -C 4 haloalkoxy of 1-3 halo radicals;

more preferably, each R 20 is independently a hydrogen, C 1 -C 4 alkyl, heteroaryl, aryl-C 1 -C 2 alkyl or heteroaryl-C 1 -C 2 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylthiol, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, acetylamino, halo, C 1 -C 4 alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R 20 is independently a hydrogen, C 1 -C 4 alkyl, aryl, heteroaryl, aryl-C 1 -C 2 alkyl or heteroaryl-C 1 -C 2 alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy;

each Z 20 is independently —O—, —S—, —S(O)—, —S(O) 2 —, —CO 2 —, —C(O)—, —NR 21 —, —NR 21 —C(O)—, —C(O)—NR 21 —, —NR 21 —S(O) 2 — or —S(O) 2 —NR 21 —; preferably, each Z 20 is independently —O— or —NR 21 —;

wherein each R 21 is independently a hydrogen or alkyl radical; preferably, each R 21 is independently a hydrogen or C 1 -C 4 alkyl radical; more preferably, each R 21 is independently a hydrogen or methyl radical;

R 5 and R 6 are each independently a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical;

preferably, R 5 and R 6 are each independently a hydrogen, C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl of 1-3 halo radicals, C 1 -C 4 haloalkoxy of 1-3 halo radicals, C 1 -C 4 aminoalkyl, (C 1 -C 4 alkyl)amino-C 1 -C 4 alkyl, di(C 1 -C 4 alkyl)amino-C 1 -C 4 alkyl, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, C 1 -C 5 alkanoylamino, C 1 -C 4 alkylsulfonylamino, aminosulfonyl, C 1 -C 4 alkylaminosulfonyl, di(C 1 -C 4 alkyl)aminosulfonyl, hydroxy, C 1 -C 4 hydroxyalkyl, thiol, C 1 -C 4 alkylthiol, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkoxy, (C 1 -C 4 alkoxy)C 1 -C 4 alkyl, cyano, azido, nitro, carboxy, (C 1 -C 4 alkoxy)carbonyl, aminocarbonyl, (C 1 -C 4 alkyl)aminocarbonyl or di(C 1 -C 4 alkyl)aminocarbonyl radical;

more preferably, R 5 and R 6 are each independently a hydrogen, C 1 -C 4 alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C 1 -C 4 alkylamino, di(C 1 -C 4 alkyl)amino, C 1 -C 5 alkanoylamino, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, cyano, azido, nitro, carboxy, (C 1 -C 4 alkoxy)carbonyl, aminocarbonyl, (C 1 -C 4 alkyl)aminocarbonyl or di(C 1 -C 4 alkyl)aminocarbonyl radical;

more preferably, R 5 and R 6 are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C 1 -C 2 alkylamino, di(C 1 -C 2 alkyl)amino, hydroxy, methoxy or ethoxy radical; most preferably, R 5 and R 6 are each a hydrogen radical;

R 7 is a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical;

preferably, R 7 is a hydrogen, C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl of 1-3 halo radicals, C 1 -C 4 haloalkoxy of 1-3 halo radicals, C 1 -C 4 aminoalkyl, (C 1 -C 4 alkyl)amino-C 1 -C 4 alkyl, di(C 1 -C 4 alkyl)amino-C 1 -C 4 alkyl, aminosulfonyl, C 1 -C 4 alkylaminosulfonyl, di(C 1 -C 4 alkyl)aminosulfonyl, hydroxy, C 1 -C 4 hydroxyalkyl, thiol, C 1 -C 4 alkylthiol, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkoxy, (C 1 -C 4 alkoxy)C 1 -C 4 alkyl, cyano, azido, nitro, carboxy, (C 1 -C 4 alkoxy)carbonyl, aminocarbonyl, (C 1 -C 4 alkyl)aminocarbonyl or di(C 1 -C 4 alkyl)aminocarbonyl radical;

more preferably, R 7 is a hydrogen, C 1 -C 4 alkyl halo, trifluoromethyl, trifluoromethoxy, hydroxy, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, carboxy, (C 1 -C 4 alkoxy)carbonyl, aminocarbonyl, (C 1 -C 4 alkyl)aminocarbonyl or di(C 1 -C 4 alkyl)aminocarbonyl radical;

more preferably, R 7 is a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, methoxy or ethoxy radical; most preferably, R 7 is a hydrogen radical.

The compounds of this invention may have in general several asymmetric centers and are typically depicted in the form of racemic mixtures. This invention is intended to encompass racemic mixtures, partially racemic mixtures and separate enantiomers and diasteromers.

Compounds of interest include the following:

2-cyclohexyloxy-5-(2-chlorophenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2-methylphenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-cyclohexyloxy-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2,4-dimethylphenoxy)-5-(2-chlorophenylcarbonylamino) pyridine;

2-(2,4-dimethylphenoxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenoxy)-5-(2-methylphenylcarbonylamino) pyridine;

2-(2,6-dimethyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino) pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2-chlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenoxy)-5-(2-chlorophenylcarbonylamino) pyridine;

2-(2-methylphenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methylphenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(4-chlorophenoxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(2-methylphenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-fluorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenoxy)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(1-naphthyloxy)-5-(2-methylphenylcarbonylamino) pyridine;

2-(1-naphthyloxy)-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-(1-naphthyloxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methyl-3-pyridyloxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-((3,5-dimethyl-4-isoxazolyl)carbonylamino)pyridine;

2-(2-methyl-4-chlorophenylthiol)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylthiol)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-cyclohexylamino-5-(2,6-dichlorophenylcarbonylamino) pyridine;

2-cyclohexylamino-5-(2,6-dimethylphenylcarbonylamino) pyridine;

2-(2-methylcyclohexylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methylcyclohexylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2-fluorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2-chlorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2,6-dichlorophenylcarbonylamino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl carbonylamino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2,6-dimethylphenyl carbonylamino)pyridine; and

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl aminocarbonyl)pyridine.

As utilized herein, the following terms shall have the following meanings:

“Alkyl”, alone or in combination, means a straight-chain or branched-chain alkyl radical containing preferably 1-15 carbon atoms (C 1 -C 15 ), more preferably 1-8 carbon atoms (C 1 -C 8 ), even more preferably 1-6 carbon atoms (C 1 -C 6 ), yet more preferably 1-4 carbon atoms (C 1 -C 4 ), still more preferably 1-3 carbon atoms (C 1 -C 3 ), and most preferably 1-2 carbon atoms (C 1 -C 2 ). Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, hexyl, octyl and the like.

“Hydroxyalkyl”, alone or in combination, means an alkyl radical as defined above wherein at least one hydrogen radical is replaced with a hydroxyl radical, preferably 1-3 hydrogen radicals are replaced by hydroxyl radicals, more preferably 1-2 hydrogen radicals are replaced by hydroxyl radicals, and most preferably one hydrogen radical is replaced by a hydroxyl radical. Examples of such radicals include hydroxymethyl, 1-, 2-hydroxyethyl, 1-, 2-, 3-hydroxypropyl, 1,3-dihydroxy-2-propyl, 1,3-dihydroxybutyl, 1,2,3,4,5,6-hexahydroxy-2-hexyl and the like.

“Alkenyl”, alone or in combination, means a straight-chain or branched-chain hydrocarbon radical having one or more double bonds, preferably 1-2 double bonds and more preferably one double bond, and containing preferably 2-15 carbon atoms (C 2 -C 15 ), more preferably 2-8 carbon atoms (C 2 -C 8 ), even more preferably 2-6 carbon atoms (C 2 -C 6 ), yet more preferably 2-4 carbon atoms (C 2 -C 4 ), and still more preferably 2-3 carbon atoms (C 2 -C 3 ). Examples of such alkenyl radicals include ethenyl, propenyl, 2-methylpropenyl, 1,4-butadienyl and the like.

“Alkoxy”, alone or in combination, means a radical of the type “R—O—” wherein “R” is an alkyl radical as defined above and “O” is an oxygen atom. Examples of such alkoxy radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butyoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like.

“Alkoxycarbonyl”, alone or in combination, means a radical of the type “R—O—C(O)—” wherein “R—O—” is an alkoxy radical as defined above and “C(O)” is a carbonyl radical.

“Alkoxycarbonylamino”, alone or in combination, means a radical of the type “R—O—C(O)—NH—” wherein “R—O—C(O)” is an alkoxycarbonyl radical as defined above, wherein the amino radical may optionally be substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl and the like.

“Alkylthio”, alone or in combination, means a radical of the type “R—S—” wherein “R” is an alkyl radical as defined above and “S” is a sulfur atom. Examples of such alkylthio radicals include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, iso-butylthio, sec-butylthio, tert-butylthio and the like.

“Alkylsulfinyl”, alone or in combination, means a radical of the type “R—S(O)—” wherein “R” is an alkyl radical as defined above and “S(O)” is a mono-oxygenated sulfur atom. Examples of such alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, iso-butylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl and the like.

“Alkylsulfonyl”, alone or in combination, means a radical of the type “R—S(O) 2 —” wherein “R” is an alkyl radical as defined above and “S(O) 2 ” is a di-oxygenated sulfur atom. Examples of such alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, iso-butylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl and the like.

“Aryl”, alone or in combination, means a phenyl or biphenyl radical, which is optionally benzo fused or heterocyclo fused and which is optionally substituted with one or more substituents selected from alkyl, alkoxy, halogen, hydroxy, amino, azido, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, alkanoylamino, amido, amidino, alkoxycarbonylamino, N-alkylamidino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, N-alkylamido, N,N-dialkylamido, aralkoxycarbonylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, oxo and the like. Examples of aryl radicals are phenyl, o-tolyl, 4-methoxyphenyl, 2-(tert-butoxy)phenyl, 3-methyl-4-methoxyphenyl, 2-CF 3 -phenyl, 2-fluorophenyl, 2-chlorophenyl, 3-nitrophenyl, 3-aminophenyl, 3-acetamidophenyl, 2-amino-3-(aminomethyl)phenyl, 6-methyl-3-acetamidophenyl, 6-methyl-2-aminophenyl, 6-methyl-2,3-diaminophenyl, 2-amino-3-methylphenyl, 4,6-dimethyl-2-aminophenyl, 4-hydroxyphenyl, 3-methyl-4-hydroxyphenyl, 4-(2-methoxyphenyl)phenyl, 2-amino-1-naphthyl, 2-naphthyl, 3-amino-2-naphthyl, 1-methyl-3-amino-2-naphthyl, 2,3-diamino-1-naphthyl, 4,8-dimethoxy-2-naphthyl and the like.

“Aralkyl” and “arylalkyl”, alone or in combination means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced by an aryl radical as defined above, such as benzyl, 1-, 2-phenylethyl, dibenzylmethyl, hydroxyphenylmethyl, methylphenylmethyl, diphenylmethyl, dichlorophenylmethyl, 4-methoxyphenylmethyl and the like.

“Aralkoxy”, alone or in combination, means an alkoxy radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced by an aryl radical as defined above, such as benzyloxy, 1-, 2-phenylethoxy, dibenzylmethoxy, hydroxyphenylmethoxy, methylphenylmethoxy, dichlorophenylmethoxy, 4-methoxyphenylmethoxy and the like.

“Aralkoxycarbonyl”, alone or in combination, means a radical of the type “R—O—C(O)—” wherein “R—O—” is an aralkoxy radical as defined above and “—C(O)—” is a carbonyl radical.

“Alkanoyl”, alone or in combination, means a radical of the type “R—C(O)—” wherein “R” is an alkyl radical as defined above and “—C(O)—” is a carbonyl radical. Examples of such alkanoyl radicals include acetyl, trifluoroacetyl, hydroxyacetyl, propionyl, butyryl, valeryl, 4-methylvaleryl, and the like.

“Alkanoylamino”, alone or in combination, means a radical of the type “R—C(O)—NH—” wherein “R—C(O)—” is an alkanoyl radical as defined above, wherein the amino radical may optionally be substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl and the like.

“Aminocarbonyl”, alone or in combination, means an amino substituted carbonyl (carbamoyl) radical, wherein the amino radical may optionally be mono- or di-substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkanoyl, alkoxycarbonyl, aralkoxycarbonyl and the like.

“Aminosulfonyl”, alone or in combination, means an amino substituted sulfonyl radical.

“Benzo”, alone or in combination, means the divalent radical C 6 H 4 =derived from benzene. “Benzo fused” forms a ring system in which benzene and a cycloalkyl or aryl group have two carbons in common, for example tetrahydronaphthylene and the like.

“Bicyclic” as used herein is intended to include both fused ring systems, such as naphthyl and β-carbolinyl, and substituted ring systems, such as biphenyl, phenylpyridyl and diphenylpiperazinyl.

“Cycloalkyl”, alone or in combination, means a saturated or partially saturated, preferably one double bond, monocyclic, bicyclic or tricyclic carbocyclic alkyl radical, preferably monocyclic, containing preferably 5-12 carbon atoms (C 5 -C 12 ), more preferably 5-10 carbon atoms (C 5 -C 10 ), even more preferably 5-7 carbon atoms (C 5 -C 7 ), which is optionally benzo fused or heterocyclo fused and which is optionally substituted as defined herein with respect to the definition of aryl. Examples of such cycloalkyl radicals include cyclopentyl, cyclohexyl, dihydroxycyclohexyl, ethylenedioxycyclohexyl, cycloheptyl, octahydronaphthyl, tetrahydronaphthyl, octahydroquinolinyl, dimethoxytetrahydronaphthyl, 2,3-dihydro-1H-indenyl, azabicyclo[3.2.1]octyl and the like.

“Heteroatoms” means nitrogen, oxygen and sulfur heteroatoms.

“Heterocyclo fused” forms a ring system in which a heterocyclyl or heteroaryl group of 5-6 ring members and a cycloalkyl or aryl group have two carbons in common, for example indole, isoquinoline, tetrahydroquinoline, methylenedioxybenzene and the like.

“Heterocyclyl” means a saturated or partially unsaturated, preferably one double bond, monocyclic or bicyclic, preferably monocyclic, heterocycle radical containing at least one, preferably 1 to 4, more preferably 1 to 3, even more preferably 1-2, nitrogen, oxygen or sulfur atom ring member and having preferably 3-8 ring members in each ring, more preferably 5-8 ring members in each ring and even more preferably 5-6 ring members in each ring. “Heterocyclyl” is intended to include sulfone and sulfoxide derivatives of sulfur ring members and N-oxides of tertiary nitrogen ring members, and carbocyclic fused, preferably 3-6 ring carbon atoms and more preferably 5-6 ring carbon atoms, and benzo fused ring systems. “Heterocyclyl” radicals may optionally be substituted on at least one, preferably 1-4, more preferably 1-3, even more preferably 1-2, carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo, thioxo, aryl, aralkyl, heteroaryl, heteroaralkyl, amidino, N-alkylamidino, alkoxycarbonylamino, alkylsulfonylamino and the like, and/or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, alkoxycarbonyl, heteroaralkyl, aryl or aralkyl radicals. More preferably, “heterocyclyl”, alone or in combination, is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals. Examples of such heterocyclyl radicals include pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiamorpholinyl, 4-benzyl-piperazin-1-yl, pyrimidinyl, tetrahydrofuryl, pyrazolidonyl, pyrazolinyl, pyridazinonyl, pyrrolidonyl, tetrahydrothienyl and its sulfoxide and sulfone derivatives, 2,3-dihydroindolyl, tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydro-1-oxo-isoquinolinyl, 2,3-dihydrobenzofuryl, benzopyranyl, methylenedioxyphenyl, ethylenedioxyphenyl and the like.

“Heteroaryl” means a monocyclic or bicyclic, preferably monocyclic, aromatic heterocycle radical, having at least one, preferably 1 to 4, more preferably 1 to 3, even more preferably 1-2, nitrogen, oxygen or sulfur atom ring members and having preferably 5-6 ring members in each ring, which is optionally saturated carbocyclic fused, preferably 3-4 carbon atoms (C 3 -C 4 ) to form 5-6 ring membered rings and which is optionally substituted as defined above with respect to the definitions of aryl. Examples of such heteroaryl groups include imidazolyl, 1-benzyloxycarbonylimidazol-4-yl, pyrrolyl, pyrazolyl, pyridyl, 3-(2-methyl)pyridyl, 3-(4-trifluoromethyl)pyridyl, pyrimidinyl, 5-(4-trifluoromethyl)pyrimidinyl, pyrazinyl, triazolyl, furyl, thienyl, oxazolyl, thiazolyl, indolyl, quinolinyl, 5,6,7,8-tetrahydroquinolyl, 5,6,7,8-tetrahydroisoquinolinyl, quinoxalinyl, benzothiazolyl, benzofuryl, benzimidazolyl, benzoxazolyl and the like.

“Heteroaralkyl” and “heteroarylalkyl,” alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced by a heteroaryl radical as defined above, such as 3-furylpropyl, 2-pyrrolyl propyl, chloroquinolinylmethyl, 2-thienylethyl, pyridylmethyl, 1-imidazolylethyl and the like.

“Halogen” and “halo”, alone or in combination, means fluoro, chloro, bromo or iodo radicals.

“Haloalkyl”, alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-3, is replaced by a halogen radical, more preferably fluoro or chloro radicals. Examples of such haloalkyl radicals include 1,1,1-trifluoroethyl, chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, bis(trifluoromethyl)methyl and the like.

“Pharmacologically acceptable salt” means a salt prepared by conventional means, and are well known by those skilled in the art. The “pharmaceutically acceptable salts” include basic salts of inorganic and organic acids, including but not limited to hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, ethanesulfonic acid, malic acid, acetic acid, oxalic acid, tartaric acid, citric acid, lactic acid, fumaric acid, succinic acid, maleic acid, salicylic acid, benzoic acid, phenylacetic acid, mandelic acid and the like. When compounds of the invention include as acidic function such as a carboxy group, then suitable pharmaceutically acceptable cation pairs for the carboxy group are well known to those skilled in the art and include alkaline, alkaline earth, ammonium, quaternary ammonium cations and the like. For additional examples of “pharmacologically acceptable salts,” see infra and Berge et al, J. Pharm. Sci. 66, 1 (1977).

“Cytokine” means a secreted protein that affects the functions of other cells, particularly as it relates to the modulation of interactions between cells of the immune system or cells involved in the inflammatory response. Examples of cytokines include but are not limited to interleukin 1 (IL-1), preferably IL-1β, interleukin 6 (IL-6), interleukin 8 (IL-8) and TNF, preferably TNF-α (tumor necroses factor-α).

“TNF, IL-1, IL-6 and/or IL-8 mediated disease or disease state” means all disease states wherein TNF, IL-1, IL-6, and/or IL-8 plays a role, either directly as TNF, IL-1, IL-6, and/or IL-8 itself, or by TNF, IL-1, IL-6, and/or IL-8 inducing another cytokine to be released. For example, a disease state in which IL-1 plays a major role, but in which the production of or action of IL-1 is a result of TNF, would be considered mediated by TNF.

“Leaving group” generally refers to groups readily displaceable by a nucleophile, such as an amine, a thiol or an alcohol nucleophile. Such leaving groups are well known in the art. Examples of such leaving groups include, but are not limited to, N-hydroxysuccinimide, N-hydroxybenzotriazole, halides, triflates, tosylates and the like. Preferred leaving groups are indicated herein where appropriate.

“Protecting group” generally refers to groups well known in the art which are used to prevent selected reactive groups, such as carboxy, amino, hydroxy, mercapto and the like, from undergoing undesired reactions, such as nucleophilic, electrophilic, oxidation, reduction and the like. Preferred protecting groups are indicated herein where appropriate. Examples of amino protecting groups include, but are not limited to, aralkyl, substituted aralkyl, cycloalkenylalkyl and substituted cycloalkenyl alkyl, allyl, substituted allyl, acyl, alkoxycarbonyl, aralkoxycarbonyl, silyl and the like. Examples of aralkyl include, but are not limited to, benzyl, ortho-methylbenzyl, trityl and benzhydryl, which can be optionally substituted with halogen, alkyl, alkoxy, hydroxy, nitro, acylamino, acyl and the like, and salts, such as phosphonium and ammonium salts. Examples of aryl groups include phenyl, naphthyl, indanyl, anthracenyl, 9-(9-phenylfluorenyl), phenanthrenyl, durenyl and the like. Examples of cycloalkenylalkyl or substituted cycloalkylenylalkyl radicals, preferably have 6-10 carbon atoms, include, but are not limited to, cyclohexenyl methyl and the like. Suitable acyl, alkoxycarbonyl and aralkoxycarbonyl groups include benzyloxycarbonyl, t-butoxycarbonyl, iso-butoxycarbonyl, benzoyl, substituted benzoyl, butyryl, acetyl, tri-fluoroacetyl, tri-chloro acetyl, phthaloyl and the like. A mixture of protecting groups can be used to protect the same group, such as a primary amino group can be protected by both an aralkyl group and an aralkoxycarbonyl group. Amino protecting groups can also form a heterocyclic ring with the nitogen to which they are attached, for example, 1,2-bis(methylene)benzene, phthalimidyl, succinimidyl, maleimidyl and the like and where these heterocyclic groups can further include adjoining aryl and cycloalkyl rings. In addition, the heterocyclic groups can be momo-, di- or tri-substituted, such as nitrophthalimidyl, Amino groups may also be protected against undesired reactions, such as oxidation, through the formation of an addition salt, such as hydrochloride, toluenesulfonic acid, triflouroacetic acid and the like. Many of the amino protecting groups are also suitable for protecting carboxy, hydroxy and mercapto groups. For example, aralkyl groups. Alkyl groups are also suitable groups for protecting hydroxy and mercapto groups, such as tert-butyl.

Silyl protecting groups are silicon atoms optionally substituted by one or more alkyl, aryl and aralkyl groups. Suitable silyl protecting groups include, but are not limited to, trimethylsilyl, triethylsilyl, tri-isopropylsilyl, tert-butyldimethylsilyl, dimethylphenylsilyl, 1,2-bis(dimethylsilyl)benzene, 1,2-bis(dimethylsilyl)ethane and diphenylmethylsilyl. Silylation of an amino groups provide mono- or di-silylamino groups. Silylation of aminoalcohol compounds can lead to a N,N,O-tri-silyl derivative. Remove of the silyl function from a silyl ether function is readily accomplished by treatment with, for example, a metal hydroxide or ammonium flouride reagent, either as a discrete reaction step or in situ during a reaction with the alcohol group. Suitable silylating agents are, for example, trimethylsilyl chloride, tert-butyl-dimethylsilyl chloride, phenyldimethylsilyl chloride, diphenylmethyl silyl chloride or their combination products with imidazole or DMF. Methods for silylation of amines and removal of silyl protecting groups are well known to those skilled in the art. Methods of preparation of these amine derivatives from corresponding amino acids, amino acid amides or amino acid esters are also well known to those skilled in the art of organic chemistry including amino acid/amino acid ester or aminoalcohol chemistry.

Protecting groups are removed under conditions which will not affect the remaining portion of the molecule. These methods are well known in the art and include acid hydrolysis, hydrogenolysis and the like. A preferred method involves removal of a protecting group, such as removal of a benzyloxycarbonyl group by hydrogenolysis utilizing palladium on carbon in a suitable solvent system such as an alcohol, acetic acid, and the like or mixtures thereof. A t-butoxycarbonyl protecting group can be removed utilizing an inorganic or organic acid, such as HCl or trifluoroacetic acid, in a suitable solvent system, such as dioxane or methylene chloride. The resulting amino salt can readily be neutralized to yield the free amine. Carboxy protecting group, such as methyl, ethyl, benzyl, tert-butyl, 4-methoxyphenylmethyl and the like, can be removed under hydrolysis and hydrogenolysis conditions well known to those skilled in the art.

The symbols used above have the following meanings:

Procedures for preparing the compounds of this invention are set forth below. It should be noted that the general procedures are shown as it relates to preparation of compounds having unspecified stereochemistry. However, such procedures are generally applicable to those compounds of a specific stereochemistry, e.g., where the stereochemistry about a group is (S) or (R). In addition, the compounds having one stereochemistry (e.g., (R)) can often be utilized to produce those having opposite stereochemistry (i.e., (S)) using well-known methods, for example, by inversion.

Preparation of Compounds of Formula I

The compounds of the present invention represented by Formula I above can be prepared utilizing the following general procedures. Hetero - aromatic Nitrogen Compounds; Pyrroles and Pyridines: Schofield, Kenneth; Plenum Press, New York, N.Y.; (1967) and Advances in Nitrogen Heterocycles: JAI Press, Greenwich, Conn.; (1995) describe procedures and references that may be useful in preparing compounds of the present invention.

2-Halo-5-nitro-pyridine analogs (2) can be treated with the appropriate amine, alcohol, phenol, or thiol (R 1 —X—H) in the presence of base or Cu(I) in an appropriate solvent, such as THF, DMF, DME, DMSO and the like, at a temperature from −20° C. to 120° C. to form 2-substituted-5-nitropyridines (3) (Scheme I). Reduction of the nitro group can be performed by treatment of (3) with hydrogen gas in the presence of palladium on carbon of Raney nickel, or alternatively, by treatment with SnCl 2 in an alcoholic solvent and in the presence or absence of HCl to obtain 2-substituted-5-aminopyridines (4). The aminopyridines (4) may be alkylated using alkylhalides and an appropriate base or by reductive alkylation employing the appropriate aldehyde or ketone in the presence of a reducing agent, such as sodium triacetoxy borohydride, borane.THF and the like, to form the substituted aminopyridines (5). Either (4) or (5) may be acylated with an appropriate acid halide (e.g., R 3 C(O)Cl or R 3 C(O)Br) in the presence of a base, such as pyridine, DMAP and the like, or alternatively may be acylated with an anhydride, either mixed or symmetrical, or alternatively may be acylated by treatment with the appropriate acid (R 3 CO 2 H) in the presence of a coupling agent such as a carbodiimide reagent to form the final product (1). Alternatively, substituted 2-bromo-5-nitropyridine analogs may be reduced to, substituted 2-bromo-5-aminopyridine analogs by the action of SnBr 2 in methanolic solvent. Subsequent acylation with an appropriate activated ester (i.e.: R 3 CO 2 H in the presence of diisopropylcarbodiimide in methylene chloride as solvent) produces 2-bromopyridine-5-carboxamide compounds of structure (5a). Coupling of (5a) with an appropriate phenol in the presence of Cu(Ac) 2 and K 2 CO 3 in DMF at 140° C. provides compounds of formula (1) where X=O.

6-Substituted-2-halo-5-nitro-pyridine analogs (6) may be prepared from 2,6-dichloro-5-nitropyridine according to the methods outlined in Scheme II. Treatment with one equivalent of an appropriate nucleophile of R 7 or a precursor thereof (such as, HO − , RO − , AcS − , NC − , RS − and the like) provide (6). Subsequent reaction to form (7) (treatment with R 1 —X—H in the presence of base or Cu(I) in an appropriate solvent, such as THF, DMF, DME, DMSO and the like, at a temperature from −20° C. to 120° C.) and (8) (reduction of the nitro group and substitution with R 4 ) is as described in Scheme I (cf. Colbry, N. L. et al.; J. Heterocyclic Chem., 21: 1521-1525 (1984); Matsumoto, Jun-ichi, et al.; J. Heterocyclic Chem., 21 673-679 (1984). (8) may be reacted with an acid halide or an activated

ester as shown in Scheme I to provide compounds of formula (1). Where R 7 =CN, compounds of formula (8) may be hydrolyzed to acids (R 7 =CO 2 H) of formula (9) using acidic media such as HBr and the like. Utilizing the appropriate N-protecting groups, acids of formula (9) may be transformed into esters, amides and alcohols. Compounds of formula (9) and derivatives described above may be be reacted with an acid halide or an activated ester as shown in Scheme I to provide compounds of formula (1). Compounds of formula (8), where R 7 =—CN, may be reduced to the primary amine (R 7 =—CH 2 NH 2 ) using reagents such as BH 3 or hydrogen gas in the presence of palladium on carbon or Raney nickel. Subsequent manipulation and reaction of the primary amine may be performed in the presence of the pyridine-5-amine substituent due to it's greater reactivity. Specifically, compounds of formula (8) where R 7 =—CH 2 NH 2 may be alkylated by treatment with an appropriate aldehyde or ketone in the presence of a reducing agent, such as sodium triacetoxy borohydride, or may be acylated by treatment with an appropriate activated ester, chloroformate, isocyanate and the like, or may be sulfonylated by treatment with an appropriate sulfonyl halide. Alternatively, substituted 3-aminopyridine intermediates may be prepared from the corresponding nicotinamide compound using Hofmann's reaction.

When R 6 and/or R 7 is an alkyl group, such as methyl, in compound (7), containing the appropriate protecting groups of or avoiding the presence of base sensitive groups, can be treated with strong base such as NaNH 2 , PhLi, NaH or the like at temperatures from −78° C. to 22° C. then treated with electrophiles, such as alkyl halides, aldehydes, ketones and the like (cf. Fuerst, Feustel; CHEMTECH; 10: 693-699 (1958); Nishigaki, S. et al.; Chem. Pharm. Bull.; 17: 1827-1831 (1969); Kaiser, Edwin M.; Tetrahedron; 39: 2055-2064 (1983)). Alternatively, the alkyl group may be halogenated and the haloalkyl group may be reacted with a nucleophile, such as an amino group, alkoxy, alkylthiol and the like.

6-Chloronicotinoyl chloride analogs (10) are treated with the appropriate amine (R 3 R 4 NH) in the presence of base in an appropriate solvent, such as dichloromethane, acetonitrile, DMF, THF and the like, at a temperature from −20° C. to 120° C. to form nicotinamides (11) as shown in Scheme III. Alternatively, 6-chloronicotinic acid analogs (12) may be coupled with the appropriate amine via an anhydride, either mixed or symmetrical, or alternatively by treatment with the appropriate amine in the presence of a coupling agent such as a carbodiimide reagent to form the amide (11). 6-Chloronicotinamide analogs (11) are treated with the appropriate R 1 —X—H in the presence of absence of base, or Cu(I) in an appropriate solvent, such as pyridine, ethylene glycol, DMF, DME, DMSO and the like, at a temperature from −20° C. to 180° C. to form the final product (13).

Substituted halopyridines may be readily prepared from the corresponding pyridones using phosphorus oxychloride or pentachloride.

Amines of formula NHR 1 R 2 and NHR 3 R 4 are commercially available or can be readily prepared by those skilled in the art from commercially available starting materials. For example, an amide, nitro or cyano group can be reduced under reducing conditions, such as in the presence of a reducing agent like lithium aluminum hydride and the like, to form the corresponding amine. Alkylation and acylation of amino groups are well known in the art. Chiral and achiral substituted amines can be prepared from chiral amino acids and amino acid amides (for example, alkyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl and the like) using methods well known in the art, such as H. Brunner, P. Hankofer, U. Holzinger, B. Treittinger and H. Schoeneberger, Eur. J. Med. Chem. 25, 35-44, 1990; M. Freifelder and R. B. Hasbrouck, J. Am. Chem. Soc. 82, 696-698, 1960; Dornow and Fust, Chem. Ber. 87, 985 1954; M. Kojima and J. Fujita, Bull. Chem. Soc. Jpn. 55, 1454-1459, 1982; W. Wheeler and D. O'Bannon, Journal of Labelled Compounds and Radiopharmaceuticals XXXI, 306, 1992; and S. Davies, N. Garrido, O. Ichihara and I. Walters, J. Chem. Soc., Chem. Commun. 1153, 1993.

Alkyl sulfonic acids, aryl sulfonic acids, heterocyclyl sulfonic acids, heteroaryl sulfonic acids, alkylmercaptans, arylmercaptans, heterocyclymercaptans, heteroarylmercaptans, alkylhalides, arylhalides, heterocycloylhalides, heteroarylhalides, and the like are commercially available or can be readily prepared from starting materials commercially available using standard methods well known in the art.

Thioether derivatives can be converted into the corresponding sulfone or sulfoxide by oxidizing the thioether derivative with a suitable oxidation agent in a suitable solvent. Suitable oxidation agents include, for example, hydrogen peroxide, sodium meta-perborate, oxone (potassium peroxy monosulfate), meta-chloroperoxybenzoic acid, periodic acid and the like, including mixtures thereof. Suitable solvents include acetic acid (for sodium meta-perborate) and, for other peracids, eithers such as THF and dioxane, and acetonitire, DMF and the like, including mixtures thereof.

The chemical reactions described above are generally disclosed in terms of their broadest application to the preparation of the compounds of this invention. Occasionally, the reactions may not be applicable as described to each compound included within the disclosed scope. The compounds for which this occurs will be readily recognized by those skilled in the art. In all such cases, either the reactions can be successfully performed by conventional modifications known to those skilled in the art, e.g., by appropriate protection of interfering groups, by changing to alternative conventional reagents, by routine modification of reaction conditions, and the like, or other reactions disclosed herein or otherwise conventional, will be applicable to the preparation of the corresponding compounds of this invention. In all preparative methods, all starting materials are known or readily prepared from known starting materials.

Prodrugs of the compounds of this invention are also contemplated by this invention. A prodrug is an active or inactive compound that is modified chemically through in vivo physicological action, such as hydrolysis, metabolism and the like, into a compound of this invention following administration of the prodrug to a patient. The suitability and techniques involved in making and using prodrugs are well known by those skilled in the art. For a general discussion of prodrugs involving esters see Svensson and Tunek Drug Metabolism Reviews 165 (1988) and Budgaard Design of Prodrugs, Elsevier (1985). Examples of a masked carboxylate anion include a variety of esters, such as alkyl (for example, methyl, ethyl), cycloalkyl (for example, cyclohexyl), aralkyl (for example, benzyl, p-methoxybenzyl), and alkylcarbonyloxyalkyl (for example, pivaloyloxymethyl). Amines have been masked as arylcarbonyloxymethyl substituted derivatives which are cleaved by esterases in vivo releasing the free drug and formaldehyde (Bungaard J. Med. Chem. 2503 (1989)). Also, drugs containing an acidic NH group, such as imidazole, imide, indole and the like, have been masked with N-acyloxymethyl groups (Bundgaard Design of Prodrugs, Elsevier (1985)). Hydroxy groups have been masked as esters and ethers. EP 039,051 (Sloan and Little, 4/11/81) discloses Mannich-base hydroxamic acid prodrugs, their preparation and use.

Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. The following Examples illustrate the preparation of compounds of the present invention and intermediates useful in preparing the compounds of the present invention.

EXAMPLE 1

Preparation of 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine

Step A: 2-(4-Chloro-2-methyl-phenoxy)-5-nitropyridine

4-Chloro-2-methylphenol (101 mg, 0.71 mmol) was dissolved in tetrahydrofuran (2.1 mL) and the solution was treated with sodium hydride (60% dispersed in mineral oil, 31 mg, 0.78 mmol). After stirring for 30 minutes at 22° C., 2-chloro-5-nitropyridine (101 mg, 0.64 mmol) was added and the reaction mixture was heated to reflux for 1 hour. The solution was cooled to ambient temperature, quenched with saturation aqueous NH 4 Cl and concentrated in vacuo. The residue was redissolved in ethyl acetate then washed 2× with saturated NaHCO 3 , saturated NaCl, dried over anhydrous Na 2 SO 4 and concentrated in vacuo.

Step B: 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine

2-(4-chloro-2-methyl-phenoxy)-5-nitropyridine (203 mg, 0.77 mmol) was dissolved in 95% ethanol (3 mL) and treated with 20% palladium hydroxide on carbon (50 mg). The reaction mixture was shaken in a hydrogen atmosphere. (40 psi) for 1 hour. The solution was filtered through celite and concentrated in vacuo. MS (m/z): 234/236 (M+H) + ; C 12 H 11 N 2 OCl requires 234.7.

EXAMPLE 2

The compounds listed in Table 1 were prepared from 2-chloro-5-nitropyridine and the appropriate alcohol, amine or thiol in the same manner as 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine was prepared.

TABLE 1
MS
(m/z)
2-(4-Chloro-2-methylphenoxy)-5-amino-pyridine 235
2-(4-Chloro-2,6-dimethylphenoxy)-5-amino-pyridine 249
2-(2-Methyl-pyridin-3-yloxy)-5-amino-pyridine 201
2-(4-Fluoro-2-methylphenoxy)-5-amino-pyridine 218
2-(2-Isopropylphenoxy)-5-amino-pyridine 228
2-(1-Naphthyloxy)-5-amino-pyridine 236
2-(Cyclohexyloxy)-5-amino-pyridine 192
2-(2-Methylphenoxy)-5-amino-pyridine 200
2-(2,4-Dimethylphenoxy)-5-amino-pyridine 214
2-(4-Chlorophenoxy)-5-amino-pyridine 222
2-(Phenoxy)-5-amino-pyridine     186
2-(2-Methylcyclohexylamino)-5-amino-pyridine 205
2-(Cyclohexylamino)-5-amino-pyridine 191
2-(2-Methylanilino)-5-amino-pyridine 199
2-(4-Chloro-2-methylanilino)-5-amino-pyridine 233
2-(2,4-Dimethylanilino)-5-amino-pyridine 212
2-(4-Chloro-2-methylthiophenoxy)-5-amino-pyridine 251

EXAMPLE 3

Preparation of 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine

Step A: 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-nitropyridine

Sodium hydride (60% in mineral oil, 1.08 g, 27 mmol) was washed 3× with hexanes then a solution of 4-chloro-2-methylphenol (3.50 g, 24.5 mmol) dissolved in tetrahydrofuran (40 mL) was added. The solution was stirred for 20 minutes then 2-chloro-3-methyl-5-nitropyridine (4.02 g, 23.3 mmol) was added and the reaction mixture was heated to reflux for 3 hours. After cooling, the mixture was concentrated in vacuo then dissolved in ethyl acetate and washed with water, 3× with saturated NaHCO 3 and saturated NaCl then dried over Na 2 So 4 and concentrated in vacuo.

Step B: 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine

2-(4-chloro-2-methyl-phenoxy)-3-methyl-5-nitropyridine (5.8 g, 20.8 mmol) was dissolved in 95% ethanol (50 mL) and treated with 20% palladium hydroxide on carbon (350 mg). The reaction mixture was shaken in a hydrogen atmosphere (40 psi) for 1 hour. The solution was filtered through celite and concentrated in vacuo followed by chromatography on SiO 2 using 1:1 ethyl acetate/hexanes as eluent. MS (m/z): 248/250 (M+H) + ; C 13 H 13 N 2 OCl requires 248.7.

EXAMPLE 4

The compounds listed in Table 2 were prepared from substituted 2-chloro-5-nitropyridine and 4-chloro-2-methylphenol in the same manner as 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine was prepared.

TABLE 2
MS
(m/z)
2-(4-Chloro-2-methyl-phenoxy)-4-methyl-5-amino- 249
pyridine
6-(4-Chloro-2-methyl-phenoxy)-2-methyl-3-amino- 249
pyridine
6-(4-Chloro-2-methyl-phenoxy)-2,3-diamino-pyridine 250

EXAMPLE 5

Preparation of N-(2-(4-Chloro-2-methyl-phenoxy)-pyridin-5-yl)-benzamide

2-(4-Chloro-2-methyl-phenoxy)-5-aminopyridine (211 mg, 0.90 mmol) was dissolved in methylene chloride (2.7 mL) then treated with triethylamine (0.19 mL, 1.35 mmol) followed by benzoyl chloride (0.13 mL, 1.12 mmol). The reaction mixture was stirred for 3 hours at 22° C. then saturated aqueous NaHCO 3 was added and the mixture was stirred for another hour. The organic layer was separated and washed 2x with 6% aqueous NaHCO 3 dried over Na 2 SO 4 and concentrated in vacuo. The residue was chromatographed on silica gel using 1:1 ethyl acetate/hexane as eluent. The product was recovered as a white solid. MS (m/z): 338/340 (M+H) + ; C 19 H 15 N 2 O 2 Cl requires 338.8.

EXAMPLE 6

The compounds listed in Table 3 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride in the same manner as N-(2-(4-Chloro-2-methyl-phenoxy)-pyridin-5-yl)-benzamide was prepared.

TABLE 3
MS
(m/z)
2-(4-Chloro-2-methyl-phenoxy)-5-(3- 340
pyridylcarbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 408
dichlorophenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-(4- 340
pyridylcarbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((4- 369
methoxyphenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((4- 409
pentylphenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-(2- 389
naphthylcarbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-(2- 345
thienylcarbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((3,5-dimethyl- 358
4-isoxazolyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((5- 383
benzo[1,3]dioxol-yl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((5-tert-butyl- 399
2-methy1-2H-pyrazol-3-yl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 395
benzo[b]thiophenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 369
methoxyphenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((3,5- 408
dichlorophenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 367
dimethylphenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 353
methylphenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 384
nitrophenyl)carbonylamino)pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 397
acetoxyphenyl)carbonylamino)pyridine
2-(4-chloro-2,6-dimethy1phenoxy)-5-((2,6- 422
dichlorophenyl)carbonylamino)pyridine
2-(4-chloro-2,6-dimethylphenoxy)-5-((2,6- 381
dimethylphenyl)carbonylamino)pyridine
2-(2-methyl-pyridin-3-yloxy)-5-((2,6- 374
dichlorophenyl)carbonylamino)pyridine
2-(2-methyl-pyridin-3-yloxy)-5-((2,6 333
dimethylphenyl)carbonylamino)pyridine
2-(2-methyl-pyridin-3-yloxy)-5-((2- 319
methylphenyl)carbonylamino)pyridine
2-(4-fluoro-2-methylphenoxy)-5-((2,6- 391
dichlorophenyl)carbonylamino)pyridine
2-(4-fluoro-2-methylphenoxy)-5-((2,6- 350
dimethylphenyl)carbonylamino)pyridine
2-(4-fluoro-2-methylphenoxy)-5-((2- 336
methylphenyl)carbonylamino)pyridine
2-(4-fluoro-2-methylphenoxy)-5-((2- 390
trifluoromethylphenyl)carbonylamino)pyridine
2-(4-fluoro-2-methylphenoxy)-5-((2- 340
fluorophenyl)carbonylamino)pyridine
2-(2-isopropylphenoxy)-5-((2,6-  401
dichlorophenyl)carbonylamino)pyridine
2-(2-isopropylphenoxy)-5-((2,6-  360
dimethylphenyl)carbonylamino)pyridine
2-(2-isopropylphenoxy)-5-((2-    346
methylphenyl)carbonylamino)pyridine
2-(1-naphthyloxy)-5-((2,6-       409
dichlorophenyl)carbonylamino)pyridine
2-(1-naphthyloxy)-5-((2,6        368
dimethylphenyl)carbonylamino)pyridine
2-(1-naphthyloxy)-5-((2-         354
methylphenyl)carbonylamino)pyridine
2-(cyclohexyloxy)-5-((2,6-       365
dichlorophenyl)carbonylamino)pyridine
2-(cyclohexyloxy)-5-((2,6-       324
dimethylphenyl)carbonylamino)pyridine
2-(cyclohexyloxy)-5-((2-         331
chlorophenyl)carbonylamino)pyridine
2-(cyclohexyloxy)-5-((2-         310
methylphenyl)carbonylamino)pyridine
2-(2-methylphenoxy)-5-((2,6-     373
dichiorophenyl)carbonylamino)pyridine
2-(2-methylphenoxy)-5-((2,6-     332
dimethylphenyl)carbonylamino)pyridine
2-(2-methylphenoxy)-5-((2-       339
chlorophenyl)carbonylamino)pyridine
2-(2-methylphenoxy)-5-((2-       318
methylphenyl)carbonylamino)pyridine
2-(2,4-dimethylphenoxy)-5-((2,6- 387
dichlorophenyl)carbonylamino)pyridine
2-(2,4-dimethylphenoxy)-5-((2,6- 346
dimethylphenyl)carbonylamino)pyridine
2-(2,4-dimethylphenoxy)-5-((2-   353
chlorophenyl)carbonylamino)pyridine
2-(2,4-dimethylphenoxy)-5-((2-   332
methylphenyl)carbonylamino)pyridine
2-(4-chlorophenoxy)-5-((2,6-     394
dichlorophenyl)carbonylamino)pyridine
2-(4-chlorophenoxy)-5-((2,6-     353
dimethylphenyl)carbonylamino)pyridine
2-(2-methylcyclohexylamino)-5-((2,6- 378
dichlorophenyl)carbonylamino)pyridine
2-(2-methylcyclohexylamino)-5-((2- 323
methylphenyl)carbonylamino)pyridine
2-(cyclohexylamino)-5-((2,6-     364
dichlorophenyl)carbonylamino)pyridine
2-(cyclohexylamino)-5-((2,6-     323
dimethylphenyl)carbonylamino)pyridine
2-(cyclohexylamino)-5-((2-       309
methylphenyl)carbonylamino)pyridine
2-(2-methylanilino)-5-((2,6-     372
dichlorophenyl)carbonylamino)pyridine
2-(2-methylanilino)-5-((2,6-     331
dimethylphenyl)carbonylamino)pyridine
2-(2-methylanilino)-5-((2-       317
methylphenyl)carbonylamino)pyridine
2-(4-chloro-2-methylanilino)-5-((2,6- 407
dichlorophenyl)carbonylamino)pyridine
2-(4-chloro-2-methylanilino)-5-((2,6- 366
dimethylphenyl)carbonylamino)pyridine
2-(4-chloro-2-methylanilino)-5-((2- 352
methylphenyl)carbonylamino)pyridine
2-(2,4-dimethylanilino)-5-((2,6- 386
dichlorophenyl)carbonylamino)pyridine
2-(2,4-dimethylanilino)-5-((2,6- 345
dimethylphenyl)carbonylamino)pyridine
2-(2,4-dimethylanilino)-5-((2-   331
methylphenyl)carbonylamino)pyridine
2-(2,4-dimethylanilino)-5-((2-   352
chlorophenyl)carbonylamino)pyridine
2-(2,4-dimethylanilino)-5-((2-   335
fluorophenyl)carbonylamino)pyridine
2-(4-chloro-2-methyl-thiophenyl)-5-((2,6- 424
dichlorophenyl)carbonylamino)pyridine
2-(4-chloro-2-methyl-thiophenyl)-5-((2,6- 383
dimethylphenyl)carbonylamino)pyridine
2-(4-chloro-2-methyl-thiophenyl)-5-((2- 369
methylphenyl)carbonylamino)pyridine

EXAMPLE 7

The compounds listed in Table 4 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride in the same manner as N-(2-(4-Chloro-2-methyl-phenoxy)-pyridin-5-yl)-benzamide was prepared.

TABLE 4
MS
(m/z)
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 422
dichlorophenyl)carbonylamino)-3-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 387
chlorophenyl)carbonylamino)-3-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 367
methylphenyl)carbonylamino)-3-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 332
dimethylphenyl)carbonylamino)-3-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 422
dichlorophenyl)carbonylamino)-4-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2-fluoro-6- 439
trifluoromethylphenyl)carbonylamino)-4-methyl-
pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,4,6- 479
triisopropylphenyl)carbonylamino)-4-methyl-
pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 367
methylphenyl)carbonylamino)6-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 387
chlorophenyl)carbonylamino)-6-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 422
dichlorophenyl)carbonylamino)6-methyl-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 423
dichlorophenyl)carbonylamino)-6-amino-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 388
chlorophenyl)carbonylamino)-6-amino-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2,6- 382
dimethylphenyl)carbonylamino)-6-amino-pyridine
2-(4-Chloro-2-methyl-phenoxy)-5-((2- 368
methylphenyl)carbonylamino)-6-amino-pyridine

EXAMPLE 8

Preparation of 2-Amino-N-(6-(4-chloro-2-methyl-phenoxy)pyridin-3-yl)-benzamide

N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-2-nitrobenzamide (301 mg, 0.7 mol) was dissolved in 95% ethanol (4 mL) and treated with 20% palladium hydroxide on carbon (Pearlman's catalyst, 50 mg) and subjected to a hydrogen atmosphere (40 psi) for 2 hours. The catalyst was removed by filtration and the solvents were removed in vacuo. The product was purified by chromatography on SiO2 using 1:1 ethyl acetate/hexanes as eluent. MS (m/z): 353/355 (M+H) + ; C 19 H 16 N 3 O 2 Cl requires 353.8.

EXAMPLE 9

Preparation of N-(6-(4-(chloro-2-methyl-phenoxy)-pyridin-3-yl)-2-hydroxy-benzamide

Acetic acid 2-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-ylcarbamoyl)-phenyl ester (304 mg, 0.77 mmol) dissolved in tetrahydrofuran (3.8 mL) was treated with an aqueous lithium hydroxide solution (1.0 M, 3.8 mL, 3.8 mmol). The solution was stirred for 30 minutes at 22° C. then quenched with aqueous saturated NH 4 Cl. The mixture was diluted with ethyl acetate then the organics were washed with water, 2x saturated NaHCO 3 , saturated NaCl, dried over Na 2 SO 4 and concentrated in vacuo. MS (m/z): 354/356 (M+H) + ; C 19 H 15 N 2 O 3 Cl requires 354.8.

EXAMPLE 10

Preparation of 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine

Step A: 2-(Cyclohexylamino)-5-nitro-pyridine

Sodium hydride (60% dispersion in mineral oil, 1.99 g, 49.8 mmol) was washed 3x with hexanes then a solution of cyclohexylamine (3.8 mL, 33.2 mmol) dissolved in tetrahydrofuran (50 mL) was added. After stirring for 30 minutes at 22° C. 2-chloro-5-nitropyridine (5.00 g, 31.5 mmol) was added and the reaction mixture was heated to reflux for 3 hours. The solution was cooled to ambient temperature, quenched with saturated aqueous NH 4 Cl and concentrated in vacuo. The residue was redissolved in ethyl acetate then washed 2x with saturated NaHCO 3 , saturated NaCl, dried over anhydrous Na 2 SO 4 and concentrated in vacuo. The product was recovered as a brown oil.

Step B: 2-(N-Cyclohexyl-N-methylamino)-5-nitro-pyridine

Sodium hydride (60% dispersion in mineral oil, 0.38 g, 9.48 mmol) was washed 3x with hexanes then a solution of 2-cyclohexylamino-5-nitropyridine (1.88 g, 8.5 mmol) dissolved in dimethylformamide (20 mL) was added. After stirring for 30 minutes at 22° C., the reaction mixture was cooled to 0° C. and methyl iodide (0.55 mL, 8.9 mmol) was added. The solution was stirred for 1.5 hours at 0° C. followed by quenching with saturated aqueous NH 4 Cl. The reaction mixture was diluted with ethyl acetate and extracted 5x with water (200 mL), saturated NaCl, dried over Na 2 SO 4 and concentrated in vacuo oil was chromatographed on SiO 2 using 2:1 hexanes/ethyl acetate as eluent.

Step C: 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine

Cyclohexyl-methyl-(5-nitro-pyridin-2-yl)-amine (1.72 g, 7.3 mmol) was dissolved in ethanol (80 mL) and treated with 20% palladium hydroxide on carbon (Pearlman's catalyst, 0.5 g) and the mixture was shaken under a hydrogen atmosphere (50 psi) for 6 hours. The catalyst was removed by filtration through celite then the filtrate was concentrated in vacuo and the resultant oil was chromotographed on SiO 2 using 1:1 ethyl acetate/hexanes as eluent. MS (m/z) 206 (M+H) • ; C 12 H 19 N 3 requires 205.3.

EXAMPLE 11

Preparation of 2-(N-(2.4-dimethylphenyl)-N-methylamino)-5-amino-pyridine

2-(N-(2,4-dimethylphenyl)-N-methylamino)-5-amino-pyridine was prepared from 1-amino-2,4-dimethylbenzene and 2-chloro-5-nitropyridine in the same manner as 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine was prepared.

EXAMPLE 12

Preparation of 2,6-Dichloro-N-(2-(N′-cyclohexyl-N′-methylamino)-pyridin-5-yl)-benzamide

2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine (26 mg, 0.13 mmol) dissolved in methylene chloride (0.25 mL) was treated with triethylamine (0.026 mL, 0.18 mmol) followed by a solution of 2,6-dichlorobenzoyl chloride (31 mg, 0.15 mol) dissolved in methylene chloride (0.15 mL). The reaction mixture was shaken at 22° C. for 18 hours followed by quenching with saturated aqueous Na 2 Cl and stirring for an additional 5 hours. The organic layer was separated and dried over Na 2 SO 4 then concentrated in vacuo. The crude product was purified by chromatography on SiO 2 using 1:1 ethyl acetate/hexane as eluent. MS (m/z): 378/380 (M+H) + ; C 19 H 21 N 3 OCl requires 377.

EXAMPLE 13

The compounds listed in Table 5 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride in the same manner as 2,6-Dichloro-N-(2-(N′-cyclohexyl-N′-methylamino)-pyridin-5-yl)-benzamide was prepared.

TABLE 5
MS
(m/z)
2-(N-cyclohexyl-N-methylamino)-5-((2,6- 378
dichlorophenyl)carbonylamino)pyridine
2-(N-cyclohexyl-N-methylamino)-5-((2- 344
chlorophenyl)carbonylamino)pyridine
2-(N-cyclohexyl-N-methylamino)-5-((2- 323
methylphenyl)carbonylamino)pyridine
2-(N-cyclohexyl-N-methylamino)-5-((2,6- 337
dimethylphenyl)carbonylamino)pyridine
2-(2,4-dimethylphenyl)-5-((2,6-  359
dimethylphenyl)carbonylamino)pyridine
2-(2,4-dimethylphenyl)-5-((2-    345
methylphenyl)carbonylamino)pyridine
2-(2,4-dimethylphenyl)-5-((2-    366
chlorophenyl)carbonylainino)pyridine
2-(2,4-dimethylphenyl)-5-((2-    349
fluorophenyl)carbonylamino)pyridine
2-(2,4-dimethylphenyl)-5-((2,6-  400
dichlorophenyl)carbonylamino)pyridine

EXAMPLE 14

Preparation of 2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine

2-(4-Chloro-2-methyl-phenoxy)-5-aminopyridine (2.15 g, 9.16 mmol) was combined with powdered sodium hydroxide (1.46 g, 36.6 mmol), potassium carbonate (1.27 g, 9.16 mmol), tetrabutyl ammonium bromide (60 mg, 0.18 mmol) and toluene (10 mL) was stirred for 1 hour at 35° C. A solution of dimethyl sulfate (0.91 mL, 9.6 mmol) dissolved in toluene (5 mL) was added slowly. The mixture was heated at 35° C. for 20 hours. After cooling, the solids were removed by filtration and the solvent was concentrated in vacuo. The desired material was purified by chromatography on SiO 2 using 30% ethyl acetate/hexanes as eluent. MS (m/z): 248/250 (M+H) + ; C 13 H 13 N 2 OCl requires 249.

EXAMPLE 15

Preparation of 2,6-Dichloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide

2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine (32 mg, 0.13 mmol) dissolved in methylene chloride (0.25 mL) was treated with triethylamine (0.026 mL, 0.18 mmol) followed by a solution of 2,6-dichlorobenzoyl chloride (31 mg, 0.15 mmol) dissolved in methylene chloride (0.15 mL). The reaction mixture was shaken at 22° C. for 18 hours followed by quenching with saturated aqueous NH 4 Cl and stirring for an additional 5 hours. The organic layer was separated and dried over Na 2 SO 4 then concentrated in vacuo. The crude product was purified by chromatography on SiO 2 using 1:1 ethyl acetate/hexane as eluent. MS (m/z): 422/424 (M+H) + ; C 20 H 15 N 2 O 2 Cl 3 requires 422.

EXAMPLE 16

Preparation of 2-Chloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide

2-Chloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared from 2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine and 2-chlorobenzoyl chloride in the same manner as 2,6-Dichloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared.

EXAMPLE 17

Preparation of 2-Methyl-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide

2-Methyl-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared from 2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino) pyridine and 2-methylbenzoyl chloride in the same manner as 2,6-Dichloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide was prepared.

EXAMPLE 18

General Procedure for the Synthesis of 2-substituted-5-acylamino-pyridines

A solution of the 2-substituted-5-aminopyridine (10 mmol), triethylamine (20 mmol) and an acid chloride (20 mmol) in ethanol free chloroform (250 mL) was shaken for 16 hours. The mixture was then diluted with saturated aqueous sodium hydrogencarbonate (50 mL) and dichloromethane (500 mL), and shaken for 30 min. The mixture was then filtered through anhydrous magnesium sulfate, washing with dichloromethane (250 mL). Concentration of the filtrate under reduced pressure afforded the desired 2-substituted-5-acylamino-pyridines.

The compounds listed in Table 6 were prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride according to the general procedure above.

	TABLE 6
			MS
	R 1 X	R 3	(m/z)
	4-chloro-2-	4-biphenyl	415
	methylphenoxy
	4-chloro-2-	3,4-dimethoxyphenyl	319
	methylphenoxy
	4-chloro-2-	2-(trifluoromethyl)phenyl	407
	methylphenoxy
	4-chloro-2-	2,4-difluorophenyl	375
	methylphenoxy
	4-chloro-2-	4-cyanophenyl	364
	methylphenoxy
	4-chloro-2-	3-(trifluoromethyl)phenyl	407
	methylphenoxy
	4-chloro-2-	3-cyanophenyl	364
	methylphenoxy
	4-chloro-2-	2-naphthyl	389
	methylphenoxy
	4-chloro-2-	2-methoxyphenyl	369
	methylphenoxy
	4-chloro-2-	3,4,5-trimethylphenyl	429
	methylphenoxy
	4-chloro-2-	4-nitrophenyl	384
	methylphenoxy
	4-chloro-2-	3,4-dichlorophenyl	408
	methylphenoxy
	4-chloro-2-	5-nitrofuran-2-yl	374
	me thylphenoxy
	4-chloro-2-	3-bromophenyl	418
	methylphenoxy
	4-chloro-2-	3-pyridyl	340
	methylphenoxy
	4-chloro-2-	2-ethoxynaphth-1-yl	433
	methylphenoxy
	4-chloro-2-	2,3-dichlorophenyl	408
	methylphenoxy
	4-chloro-2-	3-nitrophenyl	384
	methylphenoxy
	4-chloro-2-	6-chloropyrid-3-yl	374
	methylphenoxy
	4-chloro-2-	4-(trifluoromethoxy)phenyl	423
	methylphenoxy
	4-chloro-2-	2-fluoro-4-	425
	methylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2-	2-acetoxyphenyl	397
	methylphenoxy
	4-chloro-2-	5-methylisoxazol-3-yl	344
	methylphenoxy
	4-chloro-2-	2-(phenylthio)pyrid-3-yl	448
	methylphenoxy
	4-chloro-2-	2-(trifluoromethoxy)phenyl	423
	methylphenoxy
	4-chloro-2-	1-phenyl-5-propyl-pyrazin-	447
	methylphenoxy	4-yl
	4-chloro-2-	2-ethoxyphenyl	383
	methylphenoxy
	4-chloro-2-	3-chlorothien-2-yl	379
	methylphenoxy
	4-chloro-2-	3-bromothien-2-yl	424
	methylphenoxy
	4-chloro-2-	1-(2-(2-methyl)propyl)-3-	399
	methylphenoxy	methylpyrazol-5-yl
	4-chloro-2-	3,5-dichlorophenyl	408
	methylphenoxy
	4-chloro-2-	2-(propylthio)pyridin-3-yl	414
	methylphenoxy
	4-chloro-2-	2-(ethylthio)pyridin-3-yl	400
	methylphenoxy
	4-chloro-2-	3-bromopyridin-5-yl	419
	methylphenoxy
	4-chloro-2-	4-methyl-1,2,3-thiadiazol-	361
	methylphenoxy	5-yl
	4-chloro-2-	1-methyl-3-(2-(2-	399
	methylphenoxy	methyl)propyl)pyrazol-5-yl
	4-chloro-2-	3-chlorobenzo[b]thiophen-	429
	methylphenoxy	2-yl
	4-chloro-2-	4-chlorophenyl	373
	methylphenoxy
	4-chloro-2-	4-methyl-2-phenyl-1,2,3-	420
	methylphenoxy	triazol-5-yl
	4-chloro-2-	benzo[b]thiophen-2-yl	395
	methylphenoxy
	4-chloro-2-	3,4-dimethylphenyl	367
	methylphenoxy
	4-chloro-2-	2-(phenoxy)pyridin-3-yl	432
	methylphenoxy
	4-chloro-2-	2-(methylthio)pyridin-3-yl	386
	methylphenoxy
	4-chloro-2-	5-methyl-3-phenylisoxazol-	420
	methylphenoxy	4-yl
	4-chloro-2-	4-chloro-1,3-dimethyl	442
	methylphenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	4-chloro-2-	2-chloro-6-methylpyridin-	388
	methylphenoxy	4-yl
	4-chloro-2-	3,5-dimethylisoxazol-4-yl	358
	methylphenoxy
	4-chloro-2-	1-naphthyl	389
	methylphenoxy
	4-chloro-2-	2-fluorophenyl	357
	methylphenoxy
	4-chloro-2-	4-propylphenyl	381
	methylphenoxy
	4-chloro-2-	4-(trifluoromethyl)phenyl	407
	methylphenoxy
	4-chloro-2-	3-fluorophenyl	357
	methylphenoxy
	4-chloro-2-	2,6-difluorophenyl	375
	methylphenoxy
	4-chloro-2-	2-chlorophenyl	373
	methylphenoxy
	4-chloro-2-	3-(chloromethyl)phenyl	387
	methylphenoxy
	4-chloro-2-	4-(2-(2-methyl)	395
	methylphenoxy	propyl)phenyl
	4-chloro-2-	3-chlorophenyl	373
	methylphenoxy
	4-chloro-2-	2-nitrophenyl	384
	methylphenoxy
	4-chloro-2-	3,5-dimethoxyphenyl	399
	methylphenoxy
	4-chloro-2-	2,6-dichlorophenyl	408
	methylphenoxy
	4-chloro-2-	2,4-dichlorophenyl	408
	methylphenoxy
	4-chloro-2-	4-fluorophenyl	357
	methylphenoxy
	4-chloro-2-	4-butylphenyl	395
	methylphenoxy
	4-chloro-2-	2-methylphenyl	353
	methylphenoxy
	4-chloro-2-	phenyl	339
	methylphenoxy
	4-chloro-2-	4-ethylphenyl	367
	methylphenoxy
	4-chloro-2-	2,3-difluorophenyl	375
	methylphenoxy
	4-chloro-2-	2,6-dimethoxyphenyl	399
	methylphenoxy
	4-chloro-2-	2,5-difluorophenyl	375
	methylphenoxy
	4-chloro-2-	4-ethoxyphenyl	383
	methylphenoxy
	4-chloro-2-	2,4,6-trichlorophenyl	442
	methylphenoxy
	4-chloro-2-	3-methylphenyl	353
	methylphenoxy
	4-chloro-2-	2-fluoro-5-	425
	methylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2-	3-methoxyphenyl	369
	methylphenoxy
	4-chloro-2-	thien-2-yl	345
	methylphenoxy
	4-chloro-2-	2-bromophenyl	418
	methylphenoxy
	4-chloro-2-	4-bromophenyl	418
	methylphenoxy
	4-chloro-2-	4-fluoro-3-	425
	methylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2-	3-(trifluoromethoxy)phenyl	423
	methylphenoxy
	4-chloro-2-	9-fluorenon-4-yl	441
	methylphenoxy
	4-chloro-2-	isoxazol-5-yl	330
	methylphenoxy
	4-chloro-2-	benzofuroxan-5-yl	397
	methylphenoxy
	4-chloro-2-	2-chloropyrid-3-yl	374
	methylphenoxy
	4-chloro-2-	3,5-difluorophenyl	375
	methylphenoxy
	4-chloro-2-	2-(4-	446
	methylphenoxy	methylphenoxy)pyridin-3-yl
	4-chloro-2-	pyridin-4-yl	340
	methylphenoxy
	4-chloro-2-	anthraquinon-2-yl	469
	methylphenoxy
	4-chloro-2-	2-iodophenyl	465
	methylphenoxy
	1-naphthoxy	4-biphenyl	416
	1-naphthoxy	3,4-dimethoxyphenyl	400
	1-naphthoxy	2-(trifluoromethyl)phenyl	408
	1-naphthoxy	2,4-difluorophenyl	376
	1-naphthoxy	4-cyanophenyl	365
	1-naphthoxy	3-(trifluoromethyl)phenyl	408
	1-naphthoxy	3-cyanophenyl	365
	1-naphthoxy	2-naphthyl	390
	1-naphthoxy	2-methoxyphenyl	370
	1-naphthoxy	3,4,5-trimethylphenyl	430
	1-naphthoxy	4-nitrophenyl	385
	1-naphthoxy	3,4-dichlorophenyl	409
	1-naphthoxy	5-nitrofuran-2-yl	375
	1-naphthoxy	3-bromophenyl	419
	1-naphthoxy	3-pyridyl	341
	1-naphthoxy	2-ethoxynaphth-1-yl	334
	1-naphthoxy	2,3-dichlorophenyl	409
	1-naphthoxy	3-nitrophenyl	385
	1-naphthoxy	6-chloropyrid-3-yl	376
	1-naphthoxy	4-(trifluoromethoxy)phenyl	424
	1-naphthoxy	2-fluoro-4-	426
		(trifluoromethyl)phenyl
	1-naphthoxy	3-bromothiophenyl	425
	1-naphthoxy	2-acetoxyphenyl	398
	1-naphthoxy	5-methylisoxazol-3-yl	345
	1-naphthoxy	2-(phenylthio)pyrid-3-yl	449
	1-naphthoxy	2-(trifluoromethoxy)phenyl	424
	1-naphthoxy	1-phenyl-5-propylpyrazin-	448
		4-yl
	1-naphthoxy	2-ethoxyphenyl	384
	1-naphthoxy	3-chlorothien-2-yl	381
	1-naphthoxy	1-(2-(2-methyl)propyl)-3-	400
		methylpyrazol-5-yl
	1-naphthoxy	3,5-dichlorophenyl	409
	1-naphthoxy	2-(propylthio)pyridin-3-yl	415
	1-naphthoxy	2-(ethylthio)pyridin-3-yl	401
	1-naphthoxy	3-bromopyridin-5-yl	420
	1-naphthoxy	4-methyl-1,2,3-thiadiazol-	362
		5-yl
	1-naphthoxy	1-methyl-3-(2-(2-	400
		methyl)propyl)pyrazol-5-yl
	1-naphthoxy	3-chlorobenzo[b]thiophen-	431
		2-yl
	1-naphthoxy	4-chlorophenyl	375
	1-naphthoxy	4-methyl-2-phenyl-1,2,3-	421
		triazol-5-yl
	1-naphthoxy	benzo[b]thiophen-2-yl	396
	1-naphthoxy	3,4-dimethylphenyl	368
	1-naphthoxy	2-(phenoxy)pyridin-3-yl	433
	1-naphthoxy	2-(methylthio)pyridin-3-yl	387
	1-naphthoxy	5-methyl-3-phenylisoxazol-	421
		4-yl
	1-naphthoxy	4-chloro-1,3-dimethyl	444
		pyrazolo[3,4-b]pyridin-3-
		yl
	1-naphthoxy	2-chloro-6-methylpyridin-	390
		4-yl
	1-naphthoxy	3,5-dimethylisoxazol-4-yl	359
	1-naphthoxy	1-naphthyl	390
	1-naphthoxy	2-fluorophenyl	358
	1-naphthoxy	4-propylphenyl	382
	1-naphthoxy	4-(trifluoromethyl)phenyl	408
	1-naphthoxy	3-fluorophenyl	358
	1-naphthoxy	2,6-difluorophenyl	376
	1-naphthoxy	2-chlorophenyl	375
	1-naphthoxy	3-(chloromethyl)phenyl	389
	1-naphthoxy	4-(2-(2-	396
		methyl)propyl)phenyl
	1-naphthoxy	3-chlorophenyl	375
	1-naphthoxy	2-nitrophenyl	385
	1-naphthoxy	3,5-dimethoxyphenyl	400
	1-naphthoxy	2,6-dichlorophenyl	409
	1-naphthoxy	2,4-dichlorophenyl	409
	1-naphthoxy	4-fluorophenyl	358
	1-naphthoxy	4-butylphenyl	396
	1-naphthoxy	2-methylphenyl	354
	1-naphthoxy	phenyl	340
	1-naphthoxy	4-ethylphenyl	368
	1-naphthoxy	2,3-difluorophenyl	376
	1-naphthoxy	2,6-dimethoxyphenyl	400
	1-naphthoxy	3,4-difluorophenyl	376
	1-naphthoxy	2,5-difluorophenyl	376
	1-naphthoxy	4-ethoxyphenyl	384
	1-naphthoxy	2,4,6-trichlorophenyl	444
	1-naphthoxy	3-methylphenyl	354
	1-naphthoxy	2-fluoro-5-	426
		(trifluoromethyl)phenyl
	1-naphthoxy	3-methoxyphenyl	370
	1-naphthoxy	thien-2-yl	346
	1-naphthoxy	2-bromophenyl	419
	1-naphthoxy	4-bromophenyl	419
	1-naphthoxy	4-fluoro-3-	426
		(trifluoromethyl)phenyl
	1-naphthoxy	3-(trifluoromethoxy)phenyl	424
	1-naphthoxy	9-fluorenon-4-yl	442
	1-naphthoxy	isoxazol-5-yl	331
	1-naphthoxy	benzofuroxan-5-yl	398
	1-naphthoxy	2-chloropyrid-3-yl	376
	1-naphthoxy	3,5-difluorophenyl	376
	1-naphthoxy	2-(4-	447
		methylphenoxy)pyridin-3-yl
	1-naphthoxy	pyridin-4-yl	341
	1-naphthoxy	anthraquinon-2-yl	470
	1-naphthoxy	2-iodophenyl	466
	2-(2-propyl)phenoxy	4-biphenyl	408
	2-(2-propyl)phenoxy	3,4-dimethoxyphenyl	392
	2-(2-propyl)phenoxy	2-(trifluoromethyl)phenyl	400
	2-(2-propyl)phenoxy	2-4-difluorophenyl	368
	2-(2-propyl)phenoxy	4-cyanophenyl	357
	2-(2-propyl)phenoxy	3-(trifluoromethyl)phenyl	400
	2-(2-propyl)phenoxy	3-cyanophenyl	357
	2-(2-propyl)phenoxy	2-naphthyl	382
	2-(2-propyl)phenoxy	2-methoxyphenyl	362
	2-(2-propyl)phenoxy	3,4,5,-trimethylphenyl	422
	2-(2-propyl)phenoxy	4-nitrophenyl	377
	2-(2-propyl)phenoxy	3,4-dichlorophenyl	401
	2-(2-propyl)phenoxy	5-nitrofuran-2-yl	367
	2-(2-propyl)phenoxy	3-bromophenyl	411
	2-(2-propyl)phenoxy	3-pyridyl	333
	2-(2-propyl)phenoxy	2-ethoxynaphth-1-yl	426
	2-(2-propyl)phenoxy	2,3-dichlorophenyl	401
	2-(2-propyl)phenoxy	3-nitrophenyl	377
	2-(2-propyl)phenoxy	6-chloropyrid-3-yl	368
	2-(2-propyl)phenoxy	4-(trifluoromethoxy)phenyl	416
	2-(2-propyl)phenoxy	2-fluoro-4-	418
		(trifluoromethyl)phenyl
	2-(2-propyl)phenoxy	3-bromothiophenyl	417
	2-(2-propyl)phenoxy	2-acetoxyphenyl	390
	2-(2-propyl)phenoxy	5-methylisoxazol-3-yl	337
	2-(2-propyl)phenoxy	2-(phenylthio)pyrid-3-yl	442
	2-(2-propyl)phenoxy	2-(trifluoromethoxy)phenyl	416
	2-(2-propyl)phenoxy	1-phenyl-5-propylpyrazin-	441
		4-yl
	2-(2-propyl)phenoxy	2-ethoxyphenyl	376
	2-(2-propyl)phenoxy	3-chlorothien-2-yl	373
	2-(2-propyl)phenoxy	1-(2-(2-methyl)propyl)-3-	392
		methylpyrazol-5-yl
	2-(2-propyl)phenoxy	3,5-dichlorophenyl	401
	2-(2-propyl)phenoxy	2-(propylthio)pyridin-3-yl	407
	2-(2-propyl)phenoxy	2-(ethylthio)pyridin-3-yl	393
	2-(2-propyl)phenoxy	3-bromopyridin-5-yl	412
	2-(2-propyl)phenoxy	4-methyl-1,2,3-thiadiazol-	354
		5-yl
	2-(2-propyl)phenoxy	1-methyl-3-(2-(2-	392
		methyl)propyl)pyrazol-5-yl
	2-(2-propyl)phenoxy	3-chlorobenzo[b]thiophen-	423
		2-yl
	2-(2-propyl)phenoxy	4-chlorophenyl	367
	2-(2-propyl)phenoxy	4-methyl-2-phenyl-1,2,3-	413
		triazol-5-yl
	2-(2-propyl)phenoxy	benzo[b]thiophen-2-yl	388
	2-(2-propyl)phenoxy	3,4-dimethylphenyl	360
	2-(2-propyl)phenoxy	2-(phenoxy)pyridin-3-yl	425
	2-(2-propyl)phenoxy	2-(methylthio)pyridin-3-yl	379
	2-(2-propyl)phenoxy	5-methyl-3-phenylisoxazol-	413
		4-yl
	2-(2-propyl)phenoxy	4-chloro-1,3-	436
		dimethylpyrazolo[3,4-
		b]pyridin-3-yl
	2-(2-propyl)phenoxy	2-chloro-6-methylpyridin-	382
		4-yl
	2-(2-propyl)phenoxy	3,5-dimethylisoxazol-4-yl	351
	2-(2-propyl)phenoxy	1-naphthyl	382
	2-(2-propyl)phenoxy	2-fluorophenyl	350
	2-(2-propyl)phenoxy	4-propylphenyl	374
	2-(2-propyl)phenoxy	4-(trifluoromethyl)phenyl	400
	2-(2-propyl)phenoxy	3-fluorophenyl	350
	2-(2-propyl)phenoxy	2,6-difluorophenyl	368
	2-(2-propyl)phenoxy	2-chlorophenyl	367
	2-(2-propyl)phenoxy	3-(chloromethyl)phenyl	381
	2-(2-propyl)phenoxy	4-(2-(2-	388
		methyl)propyl)phenyl
	2-(2-propyl)phenoxy	3-chlorophenyl	367
	2-(2-propyl)phenoxy	2-nitrophenyl	377
	2-(2-propyl)phenoxy	3,5-dimethoxyphenyl	392
	2-(2-propyl)phenoxy	2,6-dichlorophenyl	401
	2-(2-propyl)phenoxy	2,4-dichlorophenyl	401
	2-(2-propyl)phenoxy	4-fluorophenyl	350
	2-(2-propyl)phenoxy	4-butylphenyl	388
	2-(2-propyl)phenoxy	2-methylphenyl	346
	2-(2-propyl)phenoxy	phenyl	332
	2-(2-propyl)phenoxy	4-ethylphenyl	360
	2-(2-propyl)phenoxy	2,3-difluorophenyl	368
	2-(2-propyl)phenoxy	2,6-dimethoxyphenyl	392
	2-(2-propyl)phenoxy	3,4-difluorophenyl	368
	2-(2-propyl)phenoxy	2,5-difluorophenyl	368
	2-(2-propyl)phenoxy	4-ethoxyphenyl	376
	2-(2-propyl)phenoxy	2,4,6-trichlorophenyl	436
	2-(2-propyl)phenoxy	3-methylphenyl	346
	2-(2-propyl)phenoxy	2-fluoro-5-	418
		(trifluoromethyl)phenyl
	2-(2-propyl)phenoxy	3-methoxyphenyl	362
	2-(2-propyl)phenoxy	thien-2-yl	338
	2-(2-propyl)phenoxy	2-bromophenyl	411
	2-(2-propyl)phenoxy	4-bromophenyl	411
	2 (2-propyl)phenoxy	4-fluoro-3-	418
		(trifluoromethyl)phenyl
	2-(2-propyl)phenoxy	3-(trifluoromethoxy)phenyl	416
	2-(2-propyl)phenoxy	9-fluorenon-4-yl	434
	2-(2-propyl)phenoxy	isoxazol-5-yl	323
	2-(2-propyl)phenoxy	benzofuroxan-5-yl	390
	2-(2-propyl)phenoxy	2-chloropyrid-3-yl	368
	2-(2-propyl)phenoxy	3,5-difluorophenyl	368
	2-(2-propyl)phenoxy	2-(4-	439
		methylphenoxy)pyridin-3-yl
	2-(2-propyl)phenoxy	pyridin-4-yl	333
	2-(2-propyl)phenoxy	anthraquinon-2-yl	462
	2-(2-propyl)phenoxy	2-iodophenyl	458
	3-fluoro-5-	4-biphenyl	398
	methylphenoxy
	3-fluoro-5-	3,4-dimethoxyphenyl	382
	methylphenoxy
	3-fluoro-5-	2-(trifluoromethyl)phenyl	390
	methylphenoxy
	3-fluoro-5-	2,4-difluorophenyl	358
	methylphenoxy
	3-fluoro-5-	4-cyanophenyl	347
	methylphenoxy
	3-fluoro-5-	3-(trifluoromethyl)phenyl	390
	methylphenoxy
	3-fluoro-5-	3-cyanophenyl	347
	methylphenoxy
	3-fluoro-5-	2-naphthyl	372
	methylphenoxy
	3-fluoro-5-	2-methoxyphenyl	352
	methylphenoxy
	3-fluoro-5-	3,4,5,-trimethylphenyl	412
	methylphenoxy
	3-fluoro-5-	4-nitrophenyl	367
	methylphenoxy
	3-fluoro-5-	3,4-dichlorophenyl	391
	methylphenoxy
	3-fluoro-5-	5-nitrofuran-2-yl	357
	methylphenoxy
	3-fluoro-5-	3-bromophenyl	401
	methylphenoxy
	3-fluoro-5-	3-pyridyl	323
	methylphenoxy
	3-fluoro-5-	2-ethoxynaphth-1-yl	416
	methylphenoxy
	3-fluoro-5-	2,3-dichlorophenyl	391
	methylphenoxy
	3-fluoro-5-	3-nitrophenyl	367
	methylphenoxy
	3-fluoro-5-	6-chloropyrid-3-yl	358
	methylphenoxy
	3-fluoro-5-	4-(trifluoromethoxy)phenyl	406
	methylphenoxy
	3-fluoro-5-	2-fluoro-4-	408
	methylphenoxy	(trifluoromethyl)phenyl
	3-fluoro-5-	3-bromothienyl	407
	methylphenoxy
	3-fluoro-5-	2-acetoxyphenyl	380
	methylphenoxy
	3-fluoro-5-	5-methylisoxazol-3-yl	327
	methylphenoxy
	3-fluoro-5-	2-(phenylthio)pyrid-3-yl	431
	methylphenoxy
	3-fluoro-5-	2-(trifluoromethoxy)phenyl	406
	methylphenoxy
	3-fluoro-5-	1-phenyl-5-propylpyrazin-	430
	methylphenoxy	4-yl
	3-fluoro-5-	2-ethoxyphenyl	366
	methylphenoxy
	3-fluoro-5-	3-chlorothien-2-yl	363
	methylphenoxy
	3-fluoro-5-	1-(2-(2-methyl)propyl)-3-	382
	methylphenoxy	methylpyrazol-5-yl
	3-fluoro-5-	3,5-dichlorophenyl	391
	methylphenoxy
	3-fluoro-5-	2-(propylthio)pyridin-3-yl	397
	methylphenoxy
	3-fluoro-5-	2-(ethylthio)pyridin-3-yl	383
	methylphenoxy
	3-fluoro-5-	3-bromopyridin-5-yl	402
	methylphenoxy
	3-fluoro-5-	4-methyl-1,2,3-thiadiazol-	344
	methylphenoxy	5-yl
	3-fluoro-5-	1-methyl-3-(2-(2-	382
	methylphenoxy	methyl)propyl)pyrazol-5-yl
	3-fluoro-5-	3-chlorobenzo[b]thiophen-	413
	methylphenoxy	2-yl
	3-fluoro-5-	4-chlorophenyl	357
	methylphenoxy
	3-fluoro-5-	4-methyl-2-phenyl-1,2,3-	403
	methylphenoxy	triazol-5-yl
	3-fluoro-5-	benzo[b]thiophen-2-yl	378
	methylphenoxy
	3-fluoro-5-	3,4-dimethylphenyl	350
	methylphenoxy
	3-fluoro-5-	2-(phenoxy)pyridin-3-yl	415
	methylphenoxy
	3-fluoro-5-	2-(methylthio)pyridin-3-yl	369
	methylphenoxy
	3-fluoro-5-	5-methyl-3-phenylisoxazol-	403
	methylphenoxy	4-yl
	3-fluoro-5-	4-chloro-1,3-dimethyl	426
	methylphenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	3-fluoro-5-	2-chloro-6-methylpyridin-	372
	methylphenoxy	4-yl
	3-fluoro-5-	3,5-dimethylisoxazol-4-yl	341
	methylphenoxy
	3-fluoro-5-	1-naphthyl	372
	methylphenoxy
	3-fluoro-5-	2-fluorophenyl	340
	methylphenoxy
	3-fluoro-5-	4-propylphenyl	364
	methylphenoxy
	3-fluoro-5-	4-(trifluoromethyl)phenyl	390
	methylphenoxy
	3-fluoro-5-	3-fluorophenyl	340
	methylphenoxy
	3-fluoro-5-	2,6-difluorophenyl	358
	methylphenoxy
	3-fluoro-5-	2-chlorophenyl	357
	methylphenoxy
	3-fluoro-5-	3-(chloromethyl)phenyl	371
	methylphenoxy
	3-fluoro-5-	4-(2-(2-	378
	methylphenoxy	methyl)propyl)phenyl
	3-fluoro-5-	3-chlorophenyl	357
	methylphenoxy
	3-fluoro-5-	2-nitrophenyl	367
	methylphenoxy
	3-fluoro-5-	3,5-dimethoxyphenyl	382
	methylphenoxy
	3-fluoro-5-	2,6-dichlorophenyl	391
	methylphenoxy
	3-fluoro-5-	2,4-dichlorophenyl	391
	methylphenoxy
	3-fluoro-5-	4-fluorophenyl	340
	methylphenoxy
	3-fluoro-5-	4-butylphenyl	378
	methylphenoxy
	3-fluoro-5-	2-methylphenyl	336
	methylphenoxy
	3-fluoro-5-	phenyl	322
	methylphenoxy
	3-fluoro-5-	4-ethylphenyl	350
	methylphenoxy
	3-fluoro-5-	2,3-difluorophenyl	358
	methylphenoxy
	3-fluoro-5-	2,6-dimethoxyphenyl	382
	methylphenoxy
	3-fluoro-5-	3,4-difluorophenyl	358
	methylphenoxy
	3-fluoro-5-	2,5-difluorophenyl	358
	methylphenoxy
	3-fluoro-5-	4-ethoxyphenyl	366
	methylphenoxy
	3-fluoro-5-	2,4,6-trichlorophenyl	426
	methylphenoxy
	3-fluoro-5-	3-methylphenyl	336
	methylphenoxy
	3-fluoro-5-	2-fluoro-5-	408
	methylphenoxy	(trifluoromethyl)phenyl
	3-fluoro-5-	3-methoxyphenyl	352
	methylphenoxy
	3-fluoro-5-	thien-2-yl	328
	methylphenoxy
	3-fluoro-5-	2-bromophenyl	401
	methylphenoxy
	3-fluoro-5-	4-bromophenyl	401
	methylphenoxy
	3-fluoro-5-	4-fluoro-3-	408
	methylphenoxy	(trifluoromethyl)phenyl
	3-fluoro-5-	3-(trifluoromethoxy)phenyl	406
	methylphenoxy
	3-fluoro-5-	9-fluorenon-4-yl	424
	methylphenoxy
	3-fluoro-5-	isoxazol-5-yl	313
	methylphenoxy
	3-fluoro-5-	benzofuroxan-5-yl	380
	methylphenoxy
	3-fluoro-5-	2-chloropyrid-3-yl	358
	methylphenoxy
	3-fluoro-5-	3,5-difluorophenyl	358
	methylphenoxy
	3-fluoro-5-	2-(4-	429
	methylphenoxy	methylphenoxy)pyridin-3-yl
	3-fluoro-5-	pyridin-4-yl	323
	methylphenoxy
	3-fluoro-5-	anthraquinon-2-yl	452
	methylphenoxy
	3-fluoro-5-	2-iodophenyl	448
	methylphenoxy
	2-methylpyrid-3-yloxy	4-biphenyl	381
	2-methylpyrid-3-yloxy	3,4-dimethoxyphenyl	365
	2-methylpyrid-3-yloxy	2-(trifluoromethyl)phenyl	373
	2-methylpyrid-3-yloxy	2,4-difluorophenyl	341
	2-methylpyrid-3-yloxy	4-cyanophenyl	330
	2-methylpyrid-3-yloxy	3-(trifluoromethyl)phenyl	373
	2-methylpyrid-3-yloxy	3-cyanophenyl	330
	2-methylpyrid-3-yloxy	2-naphthyl	355
	2-methylpyrid-3-yloxy	2-methoxyphenyl	335
	2-methylpyrid-3-yloxy	3,4,5-trimethylphenyl	395
	2-methylpyrid-3-yloxy	4-nitrophenyl	350
	2-methylpyrid-3-yloxy	3,4-dichlorophenyl	374
	2-methylpyrid-3-yloxy	5-nitrofuran-2-yl	340
	2-methylpyrid-3-yloxy	3-bromophenyl	384
	2-methylpyrid-3-yloxy	3-pyridyl	306
	2-methylpyrid-3-yloxy	2-ethoxynaphth-1-yl	399
	2-methylpyrid-3-yloxy	2,3-dichlorophenyl	374
	2-methylpyrid-3-yloxy	3-nitrophenyl	350
	2-methylpyrid-3-yloxy	6-chloropyrid-3-yl	341
	2-methylpyrid-3-yloxy	4-(trifluoromethoxy)phenyl	389
	2-methylpyrid-3-yloxy	2-fluoro-4-	391
		(trifluoromethyl)phenyl
	2-methylpyrid-3-yloxy	3-bromothienyl	390
	2-methylpyrid-3-yloxy	2-acetoxyphenyl	363
	2-methylpyrid-3-yloxy	5-methylisoxazol-3-yl	310
	2-methylpyrid-3-yloxy	2-(phenylthio)pyrid-3-yl	414
	2-methylpyrid-3-yloxy	2-(trifluoromethoxy)phenyl	389
	2-methylpyrid-3-yloxy	1-phenyl-5-propylpyrazin	413
		4-yl
	2-methylpyrid-3-yloxy	2-ethoxyphenyl	349
	2-methylpyrid-3-yloxy	3-chlorothien-2-yl	346
	2-methylpyrid-3-yloxy	1-(2-(2-methyl)propyl)-3-	365
		methylpyrazol-5-yl
	2-methylpyrid-3-yloxy	3,5-dichlorophenyl	374
	2-methylpyrid-3-yloxy	2-(propylthio)pyridin-3-yl	380
	2-methylpyrid-3-yloxy	2-(ethylthio)pyridin-3-yl	366
	2-methylpyrid-3-yloxy	3-bromopyridin-5-yl	385
	2-methylpyrid-3-yloxy	4-methyl-1,2,3-thiadiazol-	327
		5-yl
	2-methylpyrid-3-yloxy	1-methyl-3-(2-(2-	365
		methyl)propyl)pyrazol-5-yl
	2-methylpyrid-3-yloxy	3-chlorobenzo[b]thiophen-	396
		2-yl
	2-methylpyrid-3-yloxy	4-chlorophenyl	340
	2-methylpyrid-3-yloxy	4-methyl-2-phenyl-1,2,3-	386
		triazol-5-yl
	2-methylpyrid-3-yloxy	benzo[b]thiophen-2-yl	361
	2-methylpyrid-3-yloxy	3,4-dimethylphenyl	333
	2-methylpyrid-3-yloxy	2-(phenoxy)pyridin-3-yl	398
	2-methylpyrid-3-yloxy	2-(methylthio)pyridin-3-yl	352
	2-methylpyrid-3-yloxy	5-methyl-3-phenylisoxazol-	386
		4-yl
	2-methylpyrid-3-yloxy	4-chloro-1,3-dimethyl	409
		pyrazolo[3,4-b]pyridin-3-
		yl
	2-methylpyrid-3-yloxy	2-chloro-6-methylpyridin-	355
		4-yl
	2-methylpyrid-3-yloxy	3,5-dimethylisoxazol-4-yl	324
	2-methylpyrid-3-yloxy	1-naphthyl	355
	2-methylpyrid-3-yloxy	2-fluorophenyl	323
	2-methylpyrid-3-yloxy	4-propylphenyl	347
	2-methylpyrid-3-yloxy	4-(trifluoromethyl)phenyl	373
	2-methylpyrid-3-yloxy	3-fluorophenyl	323
	2-methylpyrid-3-yloxy	2,6-difluorophenyl	341
	2-methylpyrid-3-yloxy	2-chlorophenyl	340
	2-methylpyrid-3-yloxy	3-(chloromethyl)phenyl	354
	2-methylpyrid-3-yloxy	4-(2-(2-	361
		methyl)propyl)phenyl
	2-methylpyrid-3-yloxy	3-chlorophenyl	340
	2-methylpyrid-3-yloxy	2-nitrophenyl	350
	2-methylpyrid-3-yloxy	3,5-dimethoxyphenyl	365
	2-methylpyrid-3-yloxy	2,6-dichlorophenyl	374
	2-methylpyrid-3-yloxy	2,4-dichlorophenyl	374
	2-methylpyrid-3-yloxy	4-fluorophenyl	323
	2-methylpyrid-3-yloxy	4-butylphenyl	361
	2-methylpyrid-3-yloxy	2-methylphenyl	319
	2-methylpyrid-3-yloxy	phenyl	305
	2-methylpyrid-3-yloxy	4-ethylphenyl	333
	2-methylpyrid-3-yloxy	2,3-difluorophenyl	341
	2-methylpyrid-3-yloxy	2,6-dimethoxyphenyl	365
	2-methylpyrid-3-yloxy	3,4-difluorophenyl	341
	2-methylpyrid-3-yloxy	2,5-difluorophenyl	341
	2-methylpyrid-3-yloxy	4-ethoxyphenyl	349
	2-methylpyrid-3-yloxy	2,4,6-trichlorophenyl	409
	2-methylpyrid-3-yloxy	3-methylphenyl	319
	2-methylpyrid-3-yloxy	2-fluoro-5-	391
		(trifluoromethyl)phenyl
	2-methylpyrid-3-yloxy	3-methoxyphenyl	335
	2-methylpyrid-3-yloxy	thien-2-yl	311
	2-methylpyrid-3-yloxy	2-bromophenyl	384
	2-methylpyrid-3-yloxy	4-bromophenyl	384
	2-methylpyrid-3-yloxy	4-fluoro-3-	391
		(trifluoromethyl)phenyl
	2-methylpyrid-3-yloxy	3-(trifluoromethoxy)phenyl	389
	2-methylpyrid-3-yloxy	9-fluorenon-4-yl	407
	2-methylpyrid-3-yloxy	isoxazol-5-yl	296
	2-methylpyrid-3-yloxy	benzofuroxan-5-yl	363
	2-methylpyrid-3-yloxy	2-chloropyrid-3-yl	341
	2-methylpyrid-3-yloxy	3,5-difluorophenyl	341
	2-methylpyrid-3-yloxy	2-(4-	412
		methylphenoxy)pyridin-3-yl
	2-methylpyrid-3-yloxy	pyridin-4-yl	306
	2-methylpyrid-3-yloxy	anthraquinon-2-yl	435
	2-methylpyrid-3-yloxy	2-iodophenyl	431
	4-chloro-2, 5-	3,4-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-2,5-	2-(trifluoromethyl)phenyl	421
	dimethylphenoxy
	4-chloro-2,5-	2,4-difluorophenyl	389
	dimethylphenoxy
	4-chloro-2,5-	3-(trifluoromethyl)phenyl	421
	dimethylphenoxy
	4-chloro-2,5-	2-naphthyl	403
	dimethylphenoxy
	4-chloro-2,5-	2-methoxyphenyl	484
	dimethylphenoxy
	4-chloro-2,5-	3,4,5-trimethylphenyl	443
	dimethylphenoxy
	4-chloro-2,5-	3,4-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-2,5-	3-bromophenyl	432
	dimethylphenoxy
	4-chloro-2,5-	3-pyridyl	354
	dimethylphenoxy
	4-chloro-2,5-	2-ethoxynaphth-1-yl	447
	dimethylphenoxy
	4-chloro-2,5-	2,3-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-2,5-	6-chloropyrid-3-yl	388
	dimethylphenoxy
	4-chloro-2,5-	4-(trifluoromethoxy)phenyl	437
	dimethylphenoxy
	4-chloro-2,5-	2-fluoro-4-	439
	dimethylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2,5-	3-bromothienyl	438
	dimethylphenoxy
	4-chloro-2,5-	2-acetoxyphenyl	411
	dimethylphenoxy
	4-chloro-2,5-	5-methylisoxazol-3-yl	358
	dimethylphenoxy
	4-chloro-2,5-	2-(phenylthio)pyrid-3-yl	462
	dimethylphenoxy
	4-chloro-2,5-	2-(trifluoromethoxy)phenyl	437
	dimethylphenoxy
	4-chloro-2,5-	1-phenyl-5-propylpyrazin-	461
	dimethylphenoxy	4-yl
	4-chloro-2,5-	2-ethoxyphenyl	397
	dimethylphenoxy
	4-chloro-2,5-	3-chlorothien-2-yl	393
	dimethylphenoxy
	4-chloro-2,5-	1-(2-(2-methyl)propyl) 3	413
	dimethylphenoxy	methylpyrazol-5-yl
	4-chloro-2,5-	3,5-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-2,5-	2-(propylthio)pyridin-3-yl	428
	dimethylphenoxy
	4-chloro-2,5-	2-(ethylthio)pyridin-3-yl	414
	dimethylphenoxy
	4-chloro-2,5-	3-bromopyridin-5-yl	433
	dimethylphenoxy
	4-chloro-2,5-	4-methyl-1,2,3-thiadiazol-	375
	dimethylphenoxy	5-yl
	4-chloro-2,5-	1-methyl-3-(2-(2-	413
	dimethylphenoxy	methyl)propyl)pyrazol-5-yl
	4-chloro-2,5-	3-chlorobenzo[b]thiophen-	443
	dimethylphenoxy	2-yl
	4-chloro-2,5-	4-chlorophenyl	387
	dimethylphenoxy
	4-chloro-2,5-	4-methyl-2-phenyl-1,2,3-	434
	dimethylphenoxy	triazol-5-yl
	4-chloro-2,5-	benzo[b]thiophen-2-yl	409
	dimethylphenoxy
	4-chloro-2,5-	3,4-dimethylphenyl	381
	dimethylphenoxy
	4-chloro-2,5-	2-(phenoxy)pyridin-3-yl	446
	dimethylphenoxy
	4-chloro-2,5-	2-(methylthio)pyridin-3-yl	400
	dimethylphenoxy
	4-chloro-2,5-	5-methyl-3-phenylisoxazol-	434
	dimethylphenoxy	4-yl
	4-chloro-2,5-	4-chloro-1,3-dimethyl	456
	dimethylphenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	4-chloro-2,5-	2-chloro-6-methylpyridin-	402
	dimethylphenoxy	4-yl
	4-chloro-2,5-	3,5-dimethylisoxazol-4-yl	372
	dimethylphenoxy
	4-chloro-2,5-	1-naphthyl	403
	dimethylphenoxy
	4-chloro-2,5-	2-fluorophenyl	371
	dimethylphenoxy
	4-chloro-2,5-	4-propylphenyl	395
	dimethylphenoxy
	4-chloro-2,5-	3-fluorophenyl	371
	dimethylphenoxy
	4-chloro-2,5-	2,6-difluorophenyl	389
	dimethylphenoxy
	4-chloro-2,5-	2-chlorophenyl	387
	dimethylphenoxy
	4-chloro-2,5-	3-(chloromethyl)phenyl	401
	dimethylphenoxy
	4-chloro-2,5-	4-(2-(2-	409
	dimethylphenoxy	methyl)propyl)phenyl
	4-chloro-2,5-	3-chlorophenyl	387
	dimethylphenoxy
	4-chloro-2,5-	3,5-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-2,5-	2,6-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-2,5-	2,4-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-2,5-	4-fluorophenyl	371
	dimethylphenoxy
	4-chloro-2,5-	4-butylphenyl	409
	dimethylphenoxy
	4-chloro-2,5-	2-methylphenyl	367
	dimethylphenoxy
	4-chloro-2,5-	phenyl	353
	dimethylphenoxy
	4-chloro-2,5-	4-ethylphenyl	381
	dimethylphenoxy
	4-chloro-2,5-	2,3-difluorophenyl	389
	dimethylphenoxy
	4-chloro-2,5-	2,6-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-2,5-	3,4-difluorophenyl	389
	dimethylphenoxy
	4-chloro-2,5-	2,5-difluorophenyl	389
	dimethylphenoxy
	4-chloro-2,5-	4-ethoxyphenyl	397
	dimethylphenoxy
	4-chloro-2,5-	2,4,6-trichlorophenyl	456
	dimethylphenoxy
	4-chloro-2,5-	3-methylphenyl	367
	dimethylphenoxy
	4-chloro-2,5-	2-fluoro-5-	439
	dimethylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2,5-	3-methoxyphenyl	383
	dimethylphenoxy
	4-chloro-2,5-	2-bromophenyl	432
	dimethylphenoxy
	4-chloro-2,5-	4-bromophenyl	432
	dimethylphenoxy
	4-chloro-2,5-	4-fluoro-3-	439
	dimethylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2,5-	3-(trifluoromethoxy)phenyl	437
	dimethylphenoxy
	4-chloro-2,5-	9-fluorenon-4-yl	455
	dimethylphenoxy
	4-chloro-2,5-	isoxazol-5-yl	344
	dimethylphenoxy
	4-chloro-2,5-	benzofuroxan-5-yl	411
	dimethylphenoxy
	4-chloro-2,5-	2-chloropyrid-3-yl	388
	dimethylphenoxy
	4-chloro-2,5-	2-(4-	460
	dimethylphenoxy	methylphenoxy)pyridin-3-yl
	4-chloro-2,5-	pyridin-4-yl	354
	dimethylphenoxy
	4-chloro-2,5-	anthraquinon-2-yl	483
	dimethylphenoxy
	4-chloro-2,5-	2-iodophenyl	479
	dimethylphenoxy
	4-chloro-2,5-	4-pentylphenyl	423
	dimethylphenoxy
	4-chloro-2,5-	2-(4-chlorophenylthio)	496
	dimethylphenoxy	pyridin-3-yl
	4-chloro-2,5-	2,6-dimethylphenyl	381
	dimethylphenoxy
	4-chloro-2,5-	2,5-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-2,5-	2,5-dichloropyridin-3-yl	423
	dimethylphenoxy
	4-chloro-2,5-	2-chloro-6-methoxypyridin-	418
	dimethylphenoxy	4-yl
	4-chloro-2,5-	2,3-dichloropyridin-5-yl	423
	dimethylphenoxy
	4-chloro-2,5-	1-naphthyl	417
	dimethylphenoxy
	4-chloro-2,5-	2,4-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-2,5-	3,5-bis(trifluoromethyl)	489
	dimethylphenoxy	phenyl
	4-chloro-2,5-	2-(4-	480
	dimethylphenoxy	chlorophenoxy)pyridin-3-yl
	4-chloro-2,5-	pentafluorophenyl	443
	dimethylphenoxy
	4-methoxyphenoxy	3,4-dimethoxyphenyl	380
	4-methoxyphenoxy	2-(trifluoromethyl)phenyl	388
	4-methoxyphenoxy	2,4-difluorophenyl	356
	4-methoxyphenoxy	3-(trifluoromethyl)phenyl	388
	4-methoxyphenoxy	2-naphthyl	370
	4-methoxyphenoxy	2-methoxyphenyl	350
	4-methoxyphenoxy	3,4,5-trimethylphenyl	410
	4-methoxyphenoxy	3,4-dichlorophenyl	389
	4-methoxyphenoxy	3-bromophenyl	399
	4-methoxyphenoxy	3-pyridyl	321
	4-methoxyphenoxy	2-ethoxynaphth-1-yl	414
	4-methoxyphenoxy	2,3-dichlorophenyl	389
	4-methoxyphenoxy	6-chloropyrid-3-yl	356
	4-methoxyphenoxy	4-(trifluoromethoxy)phenyl	404
	4-methoxyphenoxy	2-fluoro-4-	406
		(trifluoromethyl)phenyl
	4-methoxyphenoxy	3-bromothienyl	405
	4-methoxyphenoxy	2-acetoxyphenyl	378
	4-methoxyphenoxy	5-methylisoxazol-3-yl	325
	4-methoxyphenoxy	2-(phenylthio)pyrid-3-yl	429
	4-methoxyphenoxy	2-(trifluoromethoxy)phenyl	404
	4-methoxyphenoxy	1-phenyl-5-propylpyrazin-	428
		4-yl
	4-methoxyphenoxy	2-ethoxyphenyl	364
	4-methoxyphenoxy	3-chlorothien-2-yl	361
	4-methoxyphenoxy	1-(2-(2-methyl)propyl)-3-	380
		methylpyrazol-5-yl
	4-methoxyphenoxy	3,5-dichlorophenyl	389
	4-methoxyphenoxy	2-(propylthio)pyridin-3-yl	395
	4-methoxyphenoxy	2-(ethylthio)pyridin-3-yl	381
	4-methoxyphenoxy	3-bromopyridin-5-yl	400
	4-methoxyphenoxy	4-methyl-1,2,3-thiadiazol-	342
		5-yl
	4-methoxyphenoxy	1-methyl-3-(2-(2-	380
		methyl)propyl)pyrazol-5-yl
	4-methoxyphenoxy	3-chlorobenzo[b]thiophen-	411
		2-yl
	4-methoxyphenoxy	4-chlorophenyl	355
	4-methoxyphenoxy	4-methyl-2-phenyl-1,2,3-	401
		triazol-5-yl
	4-methoxyphenoxy	benzo[b]thiophen-2-yl	376
	4-methoxyphenoxy	3,4-dimethylphenyl	348
	4-methoxyphenoxy	2-(phenoxy)pyridin-3-yl	413
	4-methoxyphenoxy	2-(methylthio)pyridin-3-yl	367
	4-methoxyphenoxy	5-methyl-3-phenylisoxazol-	401
		4-yl
	4-methoxyphenoxy	4-chloro-1,3-dimethyl	424
		pyrazolo[3,4-b]pyridin-3-
		yl
	4-methoxyphenoxy	2-chloro-6-methylpyridin	370
		4-yl
	4-methoxyphenoxy	3,5-dimethylisoxazol-4-yl	339
	4-methoxyphenoxy	1-naphthyl	370
	4-methoxyphenoxy	2-fluorophenyl	338
	4-methoxyphenoxy	4-propylphenyl	362
	4-methoxyphenoxy	3-fluorophenyl	338
	4-methoxyphenoxy	2,6-difluorophenyl	356
	4-methoxyphenoxy	2-chlorophenyl	355
	4-methoxyphenoxy	3-(chloromethyl)phenyl	369
	4-methoxyphenoxy	4-(2-(2-	376
		methyl)propyl)phenyl
	4-methoxyphenoxy	3-chlorophenyl	355
	4-methoxyphenoxy	3,5-dimethoxyphenyl	380
	4-methoxyphenoxy	2,6-dichlorophenyl	389
	4-methoxyphenoxy	2,4-dichlorophenyl	389
	4-methoxyphenoxy	4-fluorophenyl	338
	4-methoxyphenoxy	4-butylphenyl	376
	4-methoxyphenoxy	2-methylphenyl	334
	4-methoxyphenoxy	phenyl	320
	4-methoxyphenoxy	4-ethylphenyl	348
	4-methoxyphenoxy	2,3-difluorophenyl	356
	4-methoxyphenoxy	2,6-dimethoxyphenyl	380
	4-methoxyphenoxy	3,4-difluorophenyl	356
	4-methoxyphenoxy	2,5-difluorophenyl	356
	4-methoxyphenoxy	4-ethoxyphenyl	364
	4-methoxyphenoxy	2,4,6-trichlorophenyl	424
	4-methoxyphenoxy	3-methylphenyl	334
	4-methoxyphenoxy	2-fluoro-5-	406
		(trifluoromethyl)phenyl
	4-methoxyphenoxy	3-methoxyphenyl	350
	4-methoxyphenoxy	2-bromophenyl	399
	4-methoxyphenoxy	4-bromophenyl	399
	4-methoxyphenoxy	4-fluoro-3-	406
		(trifluoromethyl)phenyl
	4-methoxyphenoxy	3-(trifluoromethoxy)phenyl	404
	4-methoxyphenoxy	9-fluorenon-4-yl	422
	4-methoxyphenoxy	isoxazol-5-yl	311
	4-methoxyphenoxy	benzofuroxan-5-yl	378
	4-methoxyphenoxy	2-chloropyrid-3-yl	356
	4-methoxyphenoxy	2-(4-	427
		methylphenoxy)pyridin-3-yl
	4-methoxyphenoxy	pyridin-4-yl	321
	4-methoxyphenoxy	anthraquinon-2-yl	450
	4-methoxyphenoxy	2-iodophenyl	446
	4-methoxyphenoxy	4-pentylphenyl	390
	4-methoxyphenoxy	2-(4-chlorophenylthio)	464
		pyridin-3-yl
	4-methoxyphenoxy	2,6-dimethylphenyl	348
	4-methoxyphenoxy	2,5-dimethoxyphenyl	380
	4-methoxyphenoxy	2,5-dichloropyridin-3-yl	390
	4-methoxyphenoxy	2-chloro-6-methoxypyridin-	386
		4-yl
	4-methoxyphenoxy	2,3-dichloropyridin-5-yl	390
	4-methoxyphenoxy	1-naphthyl	384
	4-methoxyphenoxy	2,4-dimethoxyphenyl	380
	4-methoxyphenoxy	3,5-bis(trifluoromethyl)	456
		phenyl
	4-methoxyphenoxy	2-(4-	448
		chlorophenoxy)pyridin-3-yl
	4-methoxyphenoxy	pentafluorophenyl	410
	2-(2-propoxy)phenoxy	3,4-dimethoxyphenyl	408
	2-(2-propoxy)phenoxy	2-(trifluoromethyl)phenyl	416
	2-(2-propoxy)phenoxy	2,4-difluorophenyl	384
	2-(2-propoxy)phenoxy	3-(trifluoromethyl)phenyl	416
	2-(2-propoxy)phenoxy	2-naphthyl	398
	2-(2-propoxy)phenoxy	2-methoxyphenyl	378
	2-(2-propoxy)phenoxy	3,4,5-trimethylphenyl	438
	2-(2-propoxy)phenoxy	3,4-dichlorophenyl	417
	2-(2-propoxy)phenoxy	3-bromophenyl	427
	2-(2-propoxy)phenoxy	3-pyridyl	349
	2-(2-propoxy)phenoxy	2-ethoxynaphth-1-yl	442
	2-(2-propoxy)phenoxy	2,3-dichlorophenyl	417
	2-(2-propoxy)phenoxy	6-chloropyrid-3-yl	384
	2-(2-propoxy)phenoxy	4-(trifluoromethoxy)phenyl	432
	2-(2-propoxy)phenoxy	2-fluoro-4-	434
		(trifluoromethyl)phenyl
	2-(2-propoxy)phenoxy	3-bromothienyl	433
	2-(2-propoxy)phenoxy	2-acetoxyphenyl	406
	2-(2-propoxy)phenoxy	5-methylisoxazol-3-yl	353
	2-(2-propoxy)phenoxy	2-(phenylthio)pyrid-3-yl	458
	2-(2-propoxy)phenoxy	2-(trifluoromethoxy)phenyl	432
	2-(2-propoxy)phenoxy	1-phenyl-5-propylpyrazin-	457
		4-yl
	2-(2-propoxy)phenoxy	2-ethoxyphenyl	392
	2-(2-propoxy)phenoxy	3-chlorothien-2-yl	389
	2-(2-propoxy)phenoxy	1-(2-(2-methyl)propyl)-3-	408
		methylpyrazol-5-yl
	2-(2-propoxy)phenoxy	3,5-dichlorophenyl	417
	2-(2-propoxy)phenoxy	2-(propylthio)pyridin-3-yl	423
	2-(2-propoxy)phenoxy	2-(ethylthio)pyridin-3-yl	409
	2-(2-propoxy)phenoxy	3-bromopyridin-5-yl	428
	2-(2-propoxy)phenoxy	4-methyl-1,2,3-thiadiazol-	370
		5-yl
	2 (2-propoxy)phenoxy	1-methyl-3-(2-(2-	408
		methyl)propyl)pyrazol-5-yl
	2-(2-propoxy)phenoxy	3-chlorobenzo[b]thiophen-	439
		2-yl
	2-(2-propoxy)phenoxy	4-chlorophenyl	383
	2 (2-propoxy)phenoxy	4-methyl-2-phenyl-1,2,3-	429
		triazol-5-yl
	2-(2-propoxy)phenoxy	benzo[b]thiophen-2-yl	404
	2-(2 propoxy)phenoxy	3,4-dimethylphenyl	376
	2-(2 propoxy)phenoxy	2-(phenoxy)pyridin-3-yl	441
	2-(2 propoxy)phenoxy	2-(methylthio)pyridin-3-yl	395
	2-(2-propoxy)phenoxy	5-methyl-3-phenylisoxazol	429
		4-yl
	2-(2-propoxy)phenoxy	4-chloro-1,3-dimethyl	452
		pyrazolo[3,4-b]pyridin-3-
		yl
	2-(2-propoxy)phenoxy	2-chloro-6-methylpyridin-	398
		4-yl
	2-(2-propoxy)phenoxy	3,5-dimethylisoxazol-4-yl	367
	2-(2-propoxy)phenoxy	1-naphthyl	398
	2-(2-propoxy)phenoxy	2-ethoxyphenyl	392
	2-(2-propoxy)phenoxy	3-chlorothien-2-yl	389
	2-(2-propoxy)phenoxy	1-(2-(2-methyl)propyl)-3-	408
		methylpyrazol-5-yl
	2-(2-propoxy)phenoxy	3,5-dichlorophenyl	417
	2-(2-propoxy)phenoxy	2-(propylthio)pyridin-3-yl	423
	2-(2-propoxy)phenoxy	2-(ethylthio)pyridin-3-yl	409
	2-(2-propoxy)phenoxy	3-bromopyridin-5-yl	428
	2-(2-propoxy)phenoxy	4-methyl-1,2,3-thiadiazol-	370
		5-yl
	2-(2-propoxy)phenoxy	1-methyl-3-(2-(2-	408
		methyl)propyl)pyrazol-5-yl
	2-(2-propoxy)phenoxy	3-chlorobenzo[b]thiophen-	439
		2-yl
	2-(2-propoxy)phenoxy	4-chlorophenyl	383
	2-(2-propoxy)phenoxy	4-methyl-2-phenyl-1,2,3-	429
		triazol-5-yl
	2-(2-propoxy)phenoxy	benzo[b]thiophen-2-yl	404
	2-(2-propoxy)phenoxy	3,4-dimethylphenyl	376
	2-(2-propoxy)phenoxy	2-(phenoxy)pyridin-3-yl	441
	2-(2-propoxy)phenoxy	2-(methylthio)pyridin-3-yl	395
	2-(2-propoxy)phenoxy	5-methyl-3-phenylisoxazol	429
		4-yl
	2-(2-propoxy)phenoxy	4-chloro-1,3-dimethyl	452
		pyrazolo[3,4-b]pyridin-3-
		yl
	2-(2-propoxy)phenoxy	2-chloro-6-methylpyridin	398
		4-yl
	2-(2-propoxy)phenoxy	3,5-dimethylisoxazol-4-yl	367
	2-(2-propoxy)phenoxy	1-naphthyl	398
	2-(2-propoxy)phenoxy	2-fluorophenyl	366
	2-(2-propoxy)phenoxy	4-propylphenyl	390
	2-(2-propoxy)phenoxy	3-fluorophenyl	366
	2-(2-propoxy)phenoxy	2,6-difluorophenyl	384
	2-(2-propoxy)phenoxy	2-chlorophenyl	383
	2-(2-propoxy)phenoxy	3-(chloromethyl)phenyl	397
	2-(2-propoxy)phenoxy	4-(2-(2-	404
		(methyl)propyl)phenyl
	2-(2-propoxy)phenoxy	3-chlorophenyl	383
	2-(2-propoxy)phenoxy	3,5-dimethoxyphenyl	408
	2-(2-propoxy)phenoxy	2,5-dichlorophenyl	417
	2-(2-propoxy)phenoxy	2,4-dichlorophenyl	417
	2-(2-propoxy)phenoxy	4-fluorophenyl	366
	2-(2-propoxy)phenoxy	4-butylphenyl	404
	2-(2-propoxy)phenoxy	2-methylphenyl	362
	2-(2-propoxy)phenoxy	phenyl	348
	2-(2-propoxy)phenoxy	4-ethylphenyl	376
	2-(2-propoxy)phenoxy	2,3-difluorophenyl	384
	2-(2-propoxy)phenoxy	2,6-dimethoxyphenyl	408
	2-(2-propoxy)phenoxy	3,4-difluorophenyl	384
	2-(2-propoxy)phenoxy	2,5-difluorophenyl	384
	2-(2-propoxy)phenoxy	4-ethoxyphenyl	392
	2-(2-propoxy)phenoxy	2,4,6-trichlorophenyl	452
	2-(2-propoxy)phenoxy	3-methylphenyl	362
	2-(2-propoxy)phenoxy	2-fluoro-5-	434
		(trifluoromethyl)phenyl
	2-(2-propoxy)phenoxy	3-methoxyphenyl	378
	2-(2-propoxy)phenoxy	2-bromophenyl	427
	2-(2-propoxy)phenoxy	4-bromophenyl	427
	2-(2-propoxy)phenoxy	4-fluoro-3-	434
		(trifluoromethyl)phenyl
	2-(2-propoxy)phenoxy	3-(trifluoromethoxy)phenyl	432
	2-(2-propoxy)phenoxy	9-fluorenon-4-yl	450
	2-(2-propoxy)phenoxy	isoxazol-5-yl	339
	2-(2-propoxy)phenoxy	benzofuroxan-5-yl	406
	2-(2-propoxy)phenoxy	2-chloropyrid-3-yl	384
	2-(2-propoxy)phenoxy	2-(4-	455
		methylphenoxy)pyridin-3-yl
	2-(2-propoxy)phenoxy	pyridin-4-yl	349
	2-(2-propoxy)phenoxy	anthraquinon-2-yl	478
	2-(2-propoxy)phenoxy	2-iodophenyl	474
	2-(2-propoxy)phenoxy	4-pentylphenyl	419
	2-(2-propoxy)phenoxy	2-(4-chlorophenylthio)	492
		pyridin-3-yl
	2-(2-propoxy)phenoxy	2,6-dimethylphenyl	376
	2-(2-propoxy)phenoxy	2,5-dimethoxyphenyl	408
	2-(2-propoxy)phenoxy	2,5-dichloropyridin-3-yl	418
	2-(2-propoxy)phenoxy	2-chloro-6-methoxypyridin-	414
		4-yl
	2-(2-propoxy)phenoxy	2,3-dichloropyridin-5-yl	418
	2-(2-propoxy)phenoxy	1-naphthyl	412
	2-(2-propoxy)phenoxy	2,4-dimethoxyphenyl	408
	2-(2-propoxy)phenoxy	3,5-bis(trifluoromethyl)	484
		phenyl
	2-(2-propoxy)phenoxy	2-(4-	476
		chlorophenoxy)pyridin-3-yl
	2-(2-propoxy)phenoxy	pentafluorophenyl	438
	4-fluorophenoxy	3,4-dimethoxyphenyl	368
	4-fluorophenoxy	2-(trifluoromethyl)phenyl	376
	4-fluorophenoxy	2,4-difluorophenyl	344
	4-fluorophenoxy	3-(trifluoromethyl)phenyl	376
	4-fluorophenoxy	2-naphthyl	358
	4-fluorophenoxy	2-methoxyphenyl	338
	4-fluorophenoxy	3,4,5-trimethylphenyl	398
	4-fluorophenoxy	3,4-dichlorophenyl	377
	4-fluorophenoxy	3-bromophenyl	387
	4-fluorophenoxy	3-pyridyl	309
	4-fluorophenoxy	2-ethoxynaphth-1-yl	402
	4-fluorophenoxy	2,3-dichlorophenyl	377
	4-fluorophenoxy	6-chloropyrid-3-yl	344
	4-fluorophenoxy	4-(trifluoromethoxy)phenyl	392
	4-fluorophenoxy	2-fluoro-4-	394
		(trifluoromethyl)phenyl
	4-fluorophenoxy	3-bromothienyl	393
	4-fluorophenoxy	2-acetoxyphenyl	366
	4-fluorophenoxy	5-methylisoxazol-3-yl	313
	4-fluorophenoxy	2-(phenylthio)pyrid-3-yl	417
	4-fluorophenoxy	2-(trifluoromethoxy)phenyl	392
	4-fluorophenoxy	1-phenyl-5-propylpyrazin-	416
		4-yl
	4-fluorophenoxy	2-ethoxyphenyl	352
	4-fluorophenoxy	3-chlorothien-2-yl	349
	4-fluorophenoxy	1-(2-(2-methyl)propyl)-3-	368
		methylpyrazol-5-yl
	4-fluorophenoxy	3,5-dichlorophenyl	377
	4-fluorophenoxy	2-(propylthio)pyridin-3-yl	383
	4-fluorophenoxy	2-(ethylthio)pyridin-3-yl	369
	4-fluorophenoxy	3-bromopyridin-5-yl	388
	4-fluorophenoxy	4-methyl-1,2,3-thiadiazol-	330
		5-yl
	4-fluorophenoxy	1-methyl-3-(2-(2-	368
		methyl)propyl)pyrazol-5-yl
	4-fluorophenoxy	3-chlorobenzo[b]thiophen-	399
		2-yl
	4-fluorophenoxy	4-chlorophenyl	343
	4-fluorophenoxy	4-methyl-2-phenyl-1,2,3-	389
		triazol-5-yl
	4-fluorophenoxy	benzo[b]thiophen-2-yl	364
	4-fluorophenoxy	3,4-dimethylphenyl	336
	4-fluorophenoxy	2-(phenoxy)pyridin-3-yl	401
	4-fluorophenoxy	2-(methylthio)pyridin-3-yl	355
	4-fluorophenoxy	5-methyl-3-phenylisoxazol-	389
		4-yl
	4-fluorophenoxy	4-chloro-1,3-dimethyl	412
		pyrazolo[3,4-b]pyridin-3-
		yl
	4-fluorophenoxy	2-chloro-6-methylpyridin-	358
		4-yl
	4-fluorophenoxy	3,5-dimethylisoxazol-4-yl	327
	4-fluorophenoxy	1-naphthyl	358
	4-fluorophenoxy	2-fluorophenyl	326
	4-fluorophenoxy	4-propylphenyl	350
	4-fluorophenoxy	3-fluorophenyl	326
	4-fluorophenoxy	2,6-difluorophenyl	344
	4-fluorophenoxy	2-chlorophenyl	343
	4-fluorophenoxy	3-(chloromethyl)phenyl	357
	4-fluorophenoxy	4-(2-(2-	364
		methyl)propyl)phenyl
	4-fluorophenoxy	3-chlorophenyl	343
	4-fluorophenoxy	3,5-dimethoxyphenyl	368
	4-fluorophenoxy	2,6-dichlorophenyl	377
	4-fluorophenoxy	2,4-dichlorophenyl	377
	4-fluorophenoxy	4-fluorophenyl	326
	4-fluorophenoxy	4-butylphenyl	364
	4-fluorophenoxy	2-methylphenyl	322
	4-fluorophenoxy	phenyl	308
	4-fluorophenoxy	4-ethylphenyl	336
	4-fluorophenoxy	2,3-difluorophenyl	344
	4-fluorophenoxy	2,6-dimethoxyphenyl	368
	4-fluorophenoxy	3,4-difluorophenyl	344
	4-fluorophenoxy	2,5-difluorophenyl	344
	4-fluorophenoxy	4-ethoxyphenyl	352
	4-fluorophenoxy	2,4,6-trichlorophenyl	412
	4-fluorophenoxy	3-methylphenyl	322
	4-fluorophenoxy	2-fluoro-5-	394
		(trifluoromethyl)phenyl
	4-fluorophenoxy	3-methoxyphenyl	338
	4-fluorophenoxy	2-bromophenyl	387
	4-fluorophenoxy	4-bromophenyl	387
	4-fluorophenoxy	4-fluoro-3-	394
		(trifluoromethyl)phenyl
	4-fluorophenoxy	3-(trifluoromethoxy)phenyl	392
	4-fluorophenoxy	9-fluorenon-4-yl	410
	4-fluorophenoxy	isoxazol-5-yl	299
	4-fluorophenoxy	benzofuroxan-5-yl	366
	4-fluorophenoxy	2-chloropyrid-3-yl	344
	4-fluorophenoxy	2-(4-	415
		methylphenoxy)pyridin-3-yl
	4-fluorophenoxy	pyridin-4-yl	309
	4-fluorophenoxy	anthraquinon-2-yl	438
	4-fluorophenoxy	2-iodophenyl	434
	4-fluorophenoxy	4-pentylphenyl	378
	4-fluorophenoxy	2-(4-chlorophenylthio)	452
		pyridin-3-yl
	4-fluorophenoxy	2,6-dimethylphenyl	336
	4-fluorophenoxy	2,5-dimethoxyphenyl	368
	4-fluorophenoxy	2,5-dichloropyridin-3-yl	378
	4-fluorophenoxy	2-chloro-6-methoxypyridin-	374
		4-yl
	4-fluorophenoxy	2,3-dichloropyridin-5-yl	378
	4-fluorophenoxy	1-naphthyl	372
	4-fluorophenoxy	2,4-dimethoxyphenyl	368
	4-fluorophenoxy	3,5-	444
		bis(trifluoromethyl)phenyl
	4-fluorophenoxy	2-(4-	436
		chlorophenoxy)pyridin-3-yl
	4-fluorophenoxy	pentafluorophenyl	398
	4-chlorophenoxy	3,4-dimethoxyphenyl	385
	4-chlorophenoxy	2-(trifluoromethyl)phenyl	393
	4-chlorophenoxy	2,4-difluorophenyl	361
	4-chlorophenoxy	3-(trifluoromethyl)phenyl	393
	4-chlorophenoxy	2-naphthyl	375
	4-chlorophenoxy	2-methoxyphenyl	355
	4-chlorophenoxy	3,4,5-triethylphenyl	415
	4-chlorophenoxy	3,4-dichlorophenyl	394
	4-chlorophenoxy	3-bromophenyl	404
	4-chlorophenoxy	3-pyridyl	326
	4-chlorophenoxy	2-ethoxynaphth-1-yl	419
	4-chlorophenoxy	2,3-dichlorophenyl	394
	4-chlorophenoxy	6-chloropyrid-3-yl	360
	4-chlorophenoxy	4-(trifluoromethoxy)phenyl	409
	4-chlorophenoxy	2-fluoro-4-	411
		(trifluoromethyl)phenyl
	4-chlorophenoxy	3-bromothienyl	410
	4-chlorophenoxy	2-acetoxyphenyl	383
	4-chlorophenoxy	5-methylisoxazol-3-yl	330
	4-chlorophenoxy	2-(phenylthio)pyrid-3-yl	434
	4-chlorophenoxy	2-(trifluoromethoxy)phenyl	409
	4-chlorophenoxy	1-phenyl-5-propylpyrazin-	433
		4-yl
	4-chlorophenoxy	2-ethoxyphenyl	369
	4-chlorophenoxy	3-chlorothien-2-yl	365
	4-chlorophenoxy	1-(2-(2-methyl)propyl)-3-	385
		methylpyrazol-5-yl
	4-chlorophenoxy	3,5-dichlorophenyl	394
	4-chlorophenoxy	2-(propylthio)pyridin-3-yl	400
	4-chlorophenoxy	2-(ethylthio)pyridin-3-yl	386
	4-chlorophenoxy	3-bromopyridin-5-yl	405
	4-chlorophenoxy	4-methyl-1,2,3-thiadiazol-	347
		5-yl
	4-chlorophenoxy	1-methyl-3-(2-(2-	385
		methyl)propyl)pyrazol-5-yl
	4-chlorophenoxy	3-chlorobenzo[b]thiophen-	415
		2-yl
	4-chlorophenoxy	4-chlorophenyl	359
	4-chlorophenoxy	4-methyl-2-phenyl-1,2,3-	406
		triazol-5-yl
	4-chlorophenoxy	benzo[b]thiophen-2-yl	381
	4-chlorophenoxy	3,4-dimethylphenyl	353
	4-chlorophenoxy	2-(phenoxy)pyridin-3-yl	418
	4-chlorophenoxy	2-(methylthio)pyridin-3-yl	372
	4-chlorophenoxy	5-methyl-3-phenylisoxazol-	406
		4-yl
	4-chlorophenoxy	4-chloro-1,3-dimethyl	428
		pyrazolo[3,4-b]pyridin-3-
		yl
	4-chlorophenoxy	2-chloro-6-methylpyridin-	374
		4-yl
	4-chlorophenoxy	3,5-dimethylisoxazol-4-yl	344
	4-chlorophenoxy	1-naphthyl	375
	4-chlorophenoxy	2-fluorophenyl	343
	4-chlorophenoxy	4-propylphenyl	367
	4-chlorophenoxy	3-fluorophenyl	343
	4-chlorophenoxy	2,6-difluorophenyl	361
	4-chlorophenoxy	2-chlorophenyl	359
	4-chlorophenoxy	3-(chloromethyl)phenyl	373
	4-chlorophenoxy	4-(2-(2-	381
		methyl)propyl)phenyl
	4-chlorophenoxy	3-chlorophenyl	359
	4-chlorophenoxy	3,5-dimethoxyphenyl	385
	4-chlorophenoxy	2,6-dichlorophenyl	394
	4-chlorophenoxy	2,4-dichlorophenyl	394
	4-chlorophenoxy	4-fluorophenyl	343
	4-chlorophenoxy	4-butylphenyl	381
	4-chlorophenoxy	2-methylphenyl	339
	4-chlorophenoxy	phenyl	325
	4-chlorophenoxy	4-ethylphenyl	353
	4-chlorophenoxy	2,3-difluorophenyl	361
	4-chlorophenoxy	2,6-dimethoxyphenyl	385
	4-chlorophenoxy	3,4-difluorophenyl	361
	4-chlorophenoxy	2,5-difluorophenyl	361
	4-chlorophenoxy	4-ethoxyphenyl	369
	4-chlorophenoxy	2,4,6-trichlorophenyl	428
	4-chlorophenoxy	3-methylphenyl	339
	4-chlorophenoxy	2-fluoro-5-	411
		(trifluoromethyl)phenyl
	4-chlorophenoxy	3-methoxyphenyl	355
	4-chlorophenoxy	2-bromophenyl	404
	4-chlorophenoxy	4-bromophenyl	404
	4-chlorophenoxy	4-fluoro-3-	411
		(trifluoromethyl)phenyl
	4-chlorophenoxy	3-(trifluoromethoxy)phenyl	409
	4-chlorophenoxy	9-fluorenon-4-yl	427
	4-chlorophenoxy	isoxazol-5-yl	316
	4-chlorophenoxy	benzofuroxan-5-yl	383
	4-chlorophenoxy	2-chloropyrid-3-yl	360
	4-chlorophenoxy	2-(4-	432
		methylphenoxy)pyridin-3-yl
	4-chlorophenoxy	pyridin-4-yl	326
	4-chlorophenoxy	anthraquinon-2-yl	455
	4-chlorophenoxy	2-iodophenyl	451
	4-chlorophenoxy	4-pentylphenyl	395
	4-chlorophenoxy	2-(4-chlorophenylthio)	468
		pyridin-3-yl
	4-chlorophenoxy	2,6-dimethylphenyl	353
	4-chlorophenoxy	2,5-dimethoxyphenyl	385
	4-chlorophenoxy	2,5-dichloropyridin-3-yl	395
	4-chlorophenoxy	2-chloro-6-methoxypyridin-	390
		4-yl
	4-chlorophenoxy	2,3-dichloropyridin-5-yl	395
	4-chlorophenoxy	1-naphthyl	389
	4-chlorophenoxy	2,4-dimethoxyphenyl	385
	4-chlorophenoxy	3,5-	461
		bis(trifluoromethyl)phenyl
	4-chlorophenoxy	2-(4-	452
		chlorophenoxy)pyridin-3-yl
	4-chlorophenoxy	pentafluorophenyl	415
	2,4-difluorophenoxy	3,4-dimethoxyphenyl	386
	2,4-difluorophenoxy	2-(trifluoromethyl)phenyl	394
	2,4-difluorophenoxy	2,4-difluorophenyl	362
	2,4-difluorophenoxy	3-(trifluoromethyl)phenyl	394
	2,4-difluorophenoxy	2-naphthyl	376
	2,4-difluorophenoxy	2-methoxyphenyl	356
	2,4-difluorophenoxy	3,4,5-trimethylphenyl	416
	2,4-difluorophenoxy	3,4-dichlorophenyl	395
	2,4-difluorophenoxy	3-bromophenyl	405
	2,4-difluorophenoxy	3-pyridyl	327
	2,4-difluorophenoxy	2-ethoxynaphth-1-yl	420
	2,4-difluorophenoxy	2,3-dichlorophenyl	395
	2,4-difluorophenoxy	6-chloropyrid-3-yl	362
	2,4-difluorophenoxy	4-(trifluoromethoxy)phenyl	410
	2,4-difluorophenoxy	2-fluoro-4-	412
		(trifluoromethyl)phenyl
	2,4-difluorophenoxy	3-bromothienyl	411
	2,4-difluorophenoxy	2-acetoxyphenyl	384
	2,4-difluorophenoxy	5-methylisoxazol-3-yl	331
	2,4-difluorophenoxy	2-(phenylthio)pyrid-3-yl	435
	2,4-difluorophenoxy	2-(trifluoromethoxy)phenyl	410
	2,4-difluorophenoxy	1-phenyl-5-propylpyrazin-	434
		4-yl
	2,4-difluorophenoxy	2-ethoxyphenyl	370
	2,4-difluorophenoxy	3-chlorothien-2-yl	367
	2,4-difluorophenoxy	1-(2-(2-methyl)propyl)-3-	386
		methylpyrazol-5-yl
	2,4-difluorophenoxy	3,5-dichlorophenyl	395
	2,4-difluorophenoxy	2-(propylthio)pyridin-3-yl	401
	2,4-difluorophenoxy	2-(ethylthio)pyridin-3-yl	387
	2,4-difluorophenoxy	3-bromopyridin-5-yl	406
	2,4-difluorophenoxy	4-methyl-1,2,3-thiadiazol-	348
		5-yl
	2,4-difluorophenoxy	1-methyl-3-(2-(2-	386
		methyl)propyl)pyrazol-5-yl
	2,4-difluorophenoxy	3-chlorobenzo[b]thiophen-	417
		2-yl
	2,4-difluorophenoxy	4-chlorophenyl	361
	2,4-difluorophenoxy	4-methyl-2-phenyl-1,2,3-	407
		triazol-5-yl
	2,4-difluorophenoxy	benzo[b]thiophen-2-yl	382
	2,4-difluorophenoxy	3,4-dimethylphenyl	354
	2,4-difluorophenoxy	2-(phenoxy)pyridin-3-yl	409
	2,4-difluorophenoxy	2-(methylthio)pyridin-3-yl	373
	2,4-difluorophenoxy	5-methyl-3-phenylisoxazol-	407
		4-yl
	2,4-difluorophenoxy	4-chloro-1,3-dimethyl	430
		pyrazolo[3,4-b]pyridin-3-
		yl
	2,4-difluorophenoxy	2-chloro-6-methylpyridin-	376
		4-yl
	2,4-difluorophenoxy	3,5-dimethylisoxazol-4-yl	345
	2,4-difluorophenoxy	1-naphthyl	376
	2,4-difluorophenoxy	2-fluorophenyl	344
	2,4-difluorophenoxy	4-propylphenyl	368
	2,4-difluorophenoxy	3-fluorophenyl	344
	2,4-difluorophenoxy	2,6-difluorophenyl	362
	2,4-difluorophenoxy	2-chlorophenyl	361
	2,4-difluorophenoxy	3-(chloromethyl)phenyl	375
	2,4-difluorophenoxy	4-(2-(2-	382
		methyl)propyl)phenyl
	2,4-difluorophenoxy	3-chlorophenyl	361
	2,4-difluorophenoxy	3,5-dimethoxyphenyl	386
	2,4-difluorophenoxy	2,6-dichlorophenyl	395
	2,4-difluorophenoxy	2, 4-dichlorophenyl	392
	2,4-difluorophenoxy	4-fluorophenyl	344
	2,4-difluorophenoxy	4-butylphenyl	382
	2,4-difluorophenoxy	2-methylphenyl	340
	2,4-difluorophenoxy	phenyl	326
	2,4-difluorophenoxy	4-ethylphenyl	354
	2,4-difluorophenoxy	2,3-difluorophenyl	362
	2,4-difluorophenoxy	2,6-dimethoxyphenyl	386
	2,4-difluorophenoxy	3,4-difluorophenyl	362
	2,4-difluorophenoxy	2,5-difluorophenyl	362
	2,4-difluorophenoxy	4-ethoxyphenyl	370
	2,4-difluorophenoxy	2,4,6-trichlorophenyl	430
	2,4-difluorophenoxy	3-methylphenyl	340
	2,4-difluorophenoxy	2-fluoro-5-	412
		(trifluoromethyl)phenyl
	2,4-difluorophenoxy	3-methoxyphenyl	356
	2,4-difluorophenoxy	2-bromophenyl	405
	2,4-difluorophenoxy	4-bromophenyl	405
	2,4-difluorophenoxy	4-fluoro-3-	412
		(trifluoromethyl)phenyl
	2,4-difluorophenoxy	3-(trifluoromethoxy)phenyl	410
	2,4-difluorophenoxy	9-fluorenon-4-yl	428
	2,4-difluorophenoxy	isoxazol-5-yl	317
	2,4-difluorophenoxy	benzofuroxan-5-yl	384
	2,4-difluorophenoxy	2-chloropyrid-3-yl	362
	2,4-difluorophenoxy	2-(4-	433
		methylphenoxy)pyridin-3-yl
	2,4-difluorophenoxy	pyridin-4-yl	327
	2,4-difluorophenoxy	anthraquinon-2-yl	456
	2,4-difluorophenoxy	2-iodophenyl	452
	2,4-difluorophenoxy	4-pentylphenyl	396
	2,4-difluorophenoxy	2-(4-chlorophenylthio)	470
		pyridin-3-yl
	2,4-difluorophenoxy	2,6-dimethylphenyl	354
	2,4-difluorophenoxy	2,5-dimethoxyphenyl	386
	2,4-difluorophenoxy	2,5-dichloropyridin-3-yl	396
	2,4-difluorophenoxy	2-chloro-6-methoxypyridin-	392
		4-yl
	2,4-difluorophenoxy	2,3-dichloropyridin-5-yl	396
	2,4-difluorophenoxy	1-naphthyl	390
	2,4-difluorophenoxy	2,4-dimethoxyphenyl	386
	2,4-difluorophenoxy	3,5-	462
		bis(trifluoromethyl)phenyl
	2,4-difluorophenoxy	2-(4-	454
		chlorophenoxy)pyridin-3-yl
	2,4-difluorophenoxy	pentafluorophenyl	416
	4-thiomethylphenoxy	3,4-dimethoxyphenyl	396
	4-thiomethylphenoxy	2-(trifluoromethyl)phenyl	404
	4-thiomethylphenoxy	2,4-difluorophenyl	372
	4-thiomethylphenoxy	3-(trifluoromethyl)phenyl	404
	4-thiomethylphenoxy	2-naphthyl	386
	4-thiomethylphenoxy	2-methoxyphenyl	366
	4-thiomethylphenoxy	3,4,5,-trimethylphenyl	426
	4-thiomethylphenoxy	3,4-dichlorophenyl	405
	4-thiomethylphenoxy	3-bromophenyl	415
	4-thiomethylphenoxy	3-pyridyl	337
	4-thiomethylphenoxy	2 ethoxynaphth-1-yl	430
	4-thiomethylphenoxy	2,3-dichlorophenyl	405
	4-thiomethylphenoxy	6-chloropyrid-3-yl	372
	4-thiomethylphenoxy	4-(trifluoromethoxy)phenyl	420
	4-thiomethylphenoxy	2-fluoro-4-	422
		(trifluoromethyl)phenyl
	4-thiomethylphenoxy	3-bromothienyl	421
	4-thiomethylphenoxy	2-acetoxyphenyl	394
	4-thiomethylphenoxy	5-methylisoxazol-3-yl	341
	4-thiomethylphenoxy	2-(phenylthio)pyrid-3-yl	446
	4-thiomethylphenoxy	2-(trifluoromethoxy)phenyl	420
	4-thiomethylphenoxy	1-phenyl-5-propylpyrazin-	445
		4-yl
	4-thiomethylphenoxy	2-ethoxyphenyl	380
	4-thiomethylphenoxy	3-chlorothien-2-yl	377
	4-thiomethylphenoxy	1-(2-(2-methyl)propyl)-3-	396
		methylpyrazol-5-yl
	4-thiomethylphenoxy	3,5-dichlorophenyl	405
	4-thiomethylphenoxy	2-(propylthio)pyridin-3-yl	412
	4-thiomethylphenoxy	2-(ethylthio)pyridin-3-yl	397
	4-thiomethylphenoxy	3-bromopyridin-5-yl	416
	4-thiomethylphenoxy	4-methyl-1,2,3-thiadiazol-	358
		5-yl
	4-thiomethylphenoxy	1-methyl-3-(2-(2-	396
		methyl)propyl)pyrazol-5-yl
	4-thiomethylphenoxy	3-chlorobenzo[b]thiophen-	427
		2-yl
	4-thiomethylphenoxy	4-chlorophenyl	371
	4-thiomethylphenoxy	4-methyl-2-phenyl-1,2,3-	417
		triazol-5-yl
	4-thiomethylphenoxy	benzo[b]thiophen-2-yl	392
	4-thiomethylphenoxy	3,4-dimethylphenyl	364
	4-thiomethylphenoxy	2-(phenoxy)pyridin-3-yl	429
	4-thiomethylphenoxy	2-(methylthio)pyridin-3-yl	383
	4-thiomethylphenoxy	5-methyl-3-phenylisoxazol-	417
		4-yl
	4-thiomethylphenoxy	4-chloro-1,3-dimethyl	440
		pyrazolo[3,4-b]pyridin-3-
		yl
	4-thiomethylphenoxy	2-chloro-6-methylpyridin-	386
		4-yl
	4-thiomethylphenoxy	3,5-dimethylisoxazol-4-yl	355
	4-thiomethylphenoxy	1-naphthyl	386
	4-thiomethylphenoxy	2-fluorophenyl	354
	4-thiomethylphenoxy	4-propylphenyl	378
	4-thiomethylphenoxy	3-fluorophenyl	354
	4-thiomethylphenoxy	2,6-difluorophenyl	372
	4-thiomethylphenoxy	2-chlorophenyl	371
	4-thiomethylphenoxy	3-(chloromethyl)phenyl	385
	4-thiomethylphenoxy	4-(2-(2-	392
		methyl)propyl)phenyl
	4-thiomethylphenoxy	3-chlorophenyl	371
	4-thiomethylphenoxy	3,5-dimethoxyphenyl	396
	4-thiomethylphenoxy	2,6-dichlorophenyl	405
	4-thiomethylphenoxy	2,4-dichlorophenyl	405
	4-thiomethylphenoxy	4-fluorophenyl	354
	4-thiomethylphenoxy	4-butylphenyl	392
	4-thiomethylphenoxy	2-methylphenyl	350
	4-thiomethylphenoxy	phenyl	336
	4-thiomethylphenoxy	4-ethylphenyl	364
	4-thiomethylphenoxy	2,3-difluorophenyl	372
	4-thiomethylphenoxy	2,6-dimethoxyphenyl	396
	4-thiomethylphenoxy	3,4-difluorophenyl	372
	4-thiomethylphenoxy	2,5-difluorophenyl	372
	4-thiomethylphenoxy	4-ethoxyphenyl	380
	4-thiomethylphenoxy	2,4,6-trichlorophenyl	440
	4-thiomethylphenoxy	3-methylphenyl	350
	4-thiomethylphenoxy	2-fluoro-5-	422
		(trifluoromethyl)phenyl
	4-thiomethylphenoxy	3-methoxyphenyl	366
	4-thiomethylphenoxy	2-bromophenyl	415
	4-thiomethylphenoxy	4-bromophenyl	415
	4-thiomethylphenoxy	4-fluoro-3-	422
		(trifluoromethyl)phenyl
	4-thiomethylphenoxy	3-(trifluoromethoxy)phenyl	420
	4-thiomethylphenoxy	9-fluorenon-4-yl	438
	4-thiomethylphenoxy	isoxazol-5-yl	327
	4-thiomethylphenoxy	benzofuroxan-5-yl	394
	4-thiomethylphenoxy	2-chloropyrid-3-yl	372
	4-thiomethylphenoxy	2-(4-	443
		methylphenoxy)pyridin-3-yl
	4-thiomethylphenoxy	pyridin-4-yl	337
	4-thiomethylphenoxy	anthraquinon-2-yl	466
	4-thiomethylphenoxy	2-iodophenyl	462
	4-thiomethylphenoxy	4-pentylphenyl	407
	4-thiomethylphenoxy	2-(4-chlorophenylthio)	480
		pyridin-3-yl
	4-thiomethylphenoxy	2,6-dimethylphenyl	364
	4-thiomethylphenoxy	2,5-dimethoxyphenyl	396
	4-thiomethylphenoxy	2,5-dichloropyridin-3-yl	406
	4-thiomethylphenoxy	2-chloro-6-methoxypyridin	402
		4-yl
	4-thiomethylphenoxy	2,3-dichloropyridin-5-yl	406
	4-thiomethylphenoxy	1-naphthyl	400
	4-thiomethylphenoxy	2,4-dimethoxyphenyl	396
	4-thiomethylphenoxy	3,5-	372
		bis(trifluoromethyl)phenyl
	4-thiomethylphenoxy	2-(4-	464
		chlorophenoxy)pyridin-3-yl
	4-thiomethylphenoxy	pentafluorophenyl	426
	4-(2-(2-	3,4-dimethoxyphenyl	406
	methyl)propyl)phenoxy
	4-(2-(2-	2-(trifluoromethyl)phenyl	414
	methyl)propyl)phenoxy
	4-(2-(2-	2,4-difluorophenyl	382
	methyl)propyl)phenoxy
	4-(2-(2-	3-(trifluoromethyl)phenyl	414
	methyl)propyl)phenoxy
	4-(2-(2-	2-naphthyl	396
	methyl)propyl)phenoxy
	4-(2-(2-	2-methoxyphenyl	376
	methyl)propyl)phenoxy
	4-(2-(2-	3,4,5-trimethylphenyl	436
	methyl)propyl)phenoxy
	4-(2-(2-	3,4-dichlorophenyl	415
	methyl)propyl)phenoxy
	4-(2-(2-	3-bromophenyl	425
	methyl)propyl)phenoxy
	4-(2-(2-	3-pyridyl	347
	methyl)propyl)phenoxy
	4-(2-(2-	2-ethoxynaphth-1-yl	441
	methyl)propyl)phenoxy
	4-(2-(2-	2,3-dichlorophenyl	415
	methyl)propyl)phenoxy
	4-(2-(2-	6-chloropyrid-3-yl	382
	methyl)propyl)phenoxy
	4-(2-(2-	4-(trifluoromethoxy)phenyl	430
	methyl)propyl)phenoxy
	4-(2-(2-	2-fluoro-4-	432
	methyl)propyl)phenoxy	(trifluoromethyl)phenyl
	4-(2-(2-	3-bromothienyl	431
	methyl)propyl)phenoxy
	4-(2-(2-	2-acetoxyphenyl	404
	methyl)propyl)phenoxy
	4-(2-(2-	5-methylisoxazol-3-yl	351
	methyl)propyl)phenoxy
	4-(2-(2-	2-(phenylthio)pyrid-3-yl	456
	methyl)propyl)phenoxy
	4-(2-(2-	2-(trifluoromethoxy)phenyl	430
	methyl)propyl)phenoxy
	4-(2-(2-	1-phenyl-5-propylpyrazin-	455
	methyl)propyl)phenoxy	4-yl
	4-(2-(2-	2-ethoxyphenyl	390
	methyl)propyl)phenoxy
	4-(2-(2-	3-chlorothien-2-yl	387
	methyl)propyl)phenoxy
	4-(2-(2-	1-(2-(2-methyl)propyl)-3-	406
	methyl)propyl)phenoxy	methylpyrazol-5-yl
	4-(2-(2-	3,5-dichlorophenyl	415
	methyl)propyl)phenoxy
	4-(2-(2-	2-(propylthio)pyridin-3-yl	422
	methyl)propyl)phenoxy
	4-(2-(2-	2-(ethylthio)pyridin-3-yl	407
	methyl)propyl)phenoxy
	4-(2-(2-	3-bromopyridin-5-yl	426
	methyl)propyl)phenoxy
	4-(2-(2-	4-methyl-1,2,3-thiadiazol-	368
	methyl)propyl)phenoxy	5-yl
	4-(2-(2-	1-methyl-3-(2-(2-	406
	methyl)propyl)phenoxy	methyl)propyl)pyrazol-5-yl
	4-(2-(2-	3-chlorobenzo[b]thiophen-	437
	methyl)propyl)phenoxy	2-yl
	4-(2-(2-	4-chlorophenyl	381
	methyl)propyl)phenoxy
	4-(2-(2-	4-methyl-2-phenyl-1,2,3-	427
	methyl)propyl)phenoxy	triazol-5-yl
	4-(2-(2-	benzo[b]thiophen-2-yl	402
	methyl)propyl)phenoxy
	4-(2-(2-	3,4-dimethylphenyl	374
	methyl)propyl)phenoxy
	4-(2-(2-	2-(phenoxy)pyridin-3-yl	439
	methyl)propyl)phenoxy
	4-(2-(2-	2-(methylthio)pyridin-3-yl	393
	methyl)propyl)phenoxy
	4-(2-(2-	5-methyl-3-phenylisoxazol-	427
	methyl)propyl)phenoxy	4-yl
	4-(2-(2-	4-chloro-1,3-dimethyl	450
	methyl)propyl)phenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	4-(2-(2-	2-chloro-6-methylpyridin-	396
	methyl)propyl)phenoxy	4-yl
	4-(2-(2-	3,5-dimethylisoxazol-4-yl	365
	methyl)propyl)phenoxy
	4-(2-(2-	1-naphthyl	396
	methyl)propyl)phenoxy
	4-(2-(2-	2-fluorophenyl	364
	methyl)propyl)phenoxy
	4-(2-(2-	4-propylphenyl	388
	methyl)propyl)phenoxy
	4-(2-(2-	3-fluorophenyl	364
	methyl)propyl)phenoxy
	4-(2-(2-	2,6-difluorophenyl	382
	methyl)propyl)phenoxy
	4-(2-(2-	2-chlorophenyl	381
	methyl)propyl)phenoxy
	4-(2-(2-	3-(chloromethyl)phenyl	395
	methyl)propyl)phenoxy
	4-(2-(2-	4-(2-(2-	402
	methyl)propyl)phenoxy	methyl)propyl)phenyl
	4-(2-(2-	3-chlorophenyl	381
	methyl)propyl)phenoxy
	4-(2-(2-	3,5-dimethoxyphenyl	406
	methyl)propyl)phenoxy
	4-(2-(2-	2,6-dichlorophenyl	415
	methyl)propyl)phenoxy
	4-(2-(2-	2,4-dichlorophenyl	415
	methyl)propyl)phenoxy
	4-(2-(2-	4-fluorophenyl	364
	methyl)propyl)phenoxy
	4-(2-(2-	4-butylphenyl	402
	methyl)propyl)phenoxy
	4-(2-(2-	2-methylphenyl	360
	methyl)propyl)phenoxy
	4-(2-(2-	phenyl	346
	methyl)propyl)phenoxy
	4-(2-(2-	4-ethylphenyl	374
	methyl)propyl)phenoxy
	4-(2-(2-	2,3-difluorophenyl	382
	methyl)propyl)phenoxy
	4-(2-(2-	2,6-dimethoxyphenyl	406
	methyl)propyl)phenoxy
	4-(2-(2-	3,4-difluorophenyl	382
	methyl)propyl)phenoxy
	4-(2-(2-	2,5-difluorophenyl	382
	methyl)propyl)phenoxy
	4-(2-(2-	4-ethoxyphenyl	390
	methyl)propyl)phenoxy
	4-(2-(2-	2,4,6-trichlorophenyl	450
	methyl)propyl)phenoxy
	4-(2-(2-	3-methylphenyl	360
	methyl)propyl)phenoxy
	4-(2-(2-	2-fluoro-5-	432
	methyl)propyl)phenoxy	(trifluoromethyl)phenyl
	4-(2-(2-	3-methoxyphenyl	376
	methyl)propyl)phenoxy
	4-(2-(2-	2-bromophenyl	425
	methyl)propyl)phenoxy
	4-(2-(2-	4-bromophenyl	425
	methyl)propyl)phenoxy
	4-(2-(2-	4-fluoro-3-	432
	methyl)propyl)phenoxy	(trifluoromethyl)phenyl
	4-(2-(2-	3-(trifluoromethoxy)phenyl	430
	methyl)propyl)phenoxy
	4-(2-(2-	9-fluorenon-4-yl	448
	methyl)propyl)phenoxy
	4-(2-(2-	isoxazol-5-yl	338
	methyl)propyl)phenoxy
	4-(2-(2-	benzofuroxan-5-yl	404
	methyl)propyl)phenoxy
	4-(2-(2-	2-chloropyrid-3-yl	382
	methyl)propyl)phenoxy
	4-(2-(2-	2-(4-	454
	methyl)propyl)phenoxy	methylphenoxy)pyridin-3-yl
	4-(2-(2-	pyridin-4-yl	347
	methyl)propyl)phenoxy
	4-(2-(2-	anthraquinon-2-yl	476
	methyl)propyl)phenoxy
	4-(2-(2-	2-iodophenyl	472
	methyl)propyl)phenoxy
	4-(2-(2-	4-pentylphenyl	417
	methyl)propyl)phenoxy
	4-(2-(2-	2-(4-chlorophenylthio)	490
	methyl)propyl)phenoxy	pyridin-3-yl
	4-(2-(2-	2,6-dimethylphenyl	374
	methyl)propyl)phenoxy
	4-(2-(2-	2,5-dimethoxyphenyl	406
	methyl)propyl)phenoxy
	4-(2-(2-	2,5-dichloropyridin-3-yl	416
	methyl)propyl)phenoxy
	4-(2-(2-	2-chloro-6-methoxypyridin-	412
	methyl)propyl)phenoxy	4-yl
	4-(2-(2-	2,3-dichloropyridin-5-yl	416
	methyl)propyl)phenoxy
	4-(2-(2-	1-naphthyl	410
	methyl)propyl)phenoxy
	4-(2-(2-	2,4-dimethoxyphenyl	406
	methyl)propyl)phenoxy
	4-(2-(2-	3,5-bis(trifluoromethyl)	482
	methyl)propyl)phenoxy	phenyl
	4-(2-(2-	2-(4-	474
	methyl)propyl)phenoxy	chlorophenoxy)pyridin-3-yl
	4-(2-(2-	pentafluorophenyl	436
	methyl)propyl)phenoxy
	2,3-dimethylphenoxy	3,4-dimethoxyphenyl	378
	2,3-dimethylphenoxy	2-(trifluoromethyl)phenyl	386
	2,3-dimethylphenoxy	2,4-difluorophenyl	354
	2,3-dimethylphenoxy	3-(trifluoromethyl)phenyl	386
	2,3-dimethylphenoxy	2-naphthyl	368
	2,3-dimethylphenoxy	2-methoxyphenyl	348
	2,3-dimethylphenoxy	3,4,5-trimethylphenyl	408
	2,3-dimethylphenoxy	3,4-dichlorophenyl	387
	2,3-dimethylphenoxy	3-bromophenyl	397
	2,3-dimethylphenoxy	3-pyridyl	319
	2,3-dimethylphenoxy	2-ethoxynaphth-1-yl	412
	2,3-dimethylphenoxy	2,3-dichlorophenyl	387
	2,3-dimethylphenoxy	6-chloropyrid-3-yl	354
	2,3-dimethylphenoxy	4-(trifluoromethoxy)phenyl	402
	2,3-dimethylphenoxy	2-fluoro-4-	404
		(trifluoromethyl)phenyl
	2,3-dimethylphenoxy	3-bromothienyl	403
	2,3-dimethylphenoxy	2-acetoxyphenyl	376
	2,3-dimethylphenoxy	5-methylisoxazol-3-yl	323
	2,3-dimethylphenoxy	2-(phenylthio)pyrid-3-yl	427
	2,3-dimethylphenoxy	2-(trifluoromethoxy)phenyl	402
	2,3-dimethylphenoxy	1-phenyl-5-propylpyrazin-	426
		4-yl
	2,3-dimethylphenoxy	2-ethoxyphenyl	362
	2,3-dimethylphenoxy	3-chlorothien-2-yl	359
	2,3-dimethylphenoxy	1-(2-(2-methyl)propyl)-3-	378
		methylpyrazol-5-yl
	2,3-dimethylphenoxy	3,5-dichlorophenyl	387
	2,3-dimethylphenoxy	2-(propylthio)pyridin-3-yl	393
	2,3-dimethylphenoxy	2-(ethylthio)pyridin-3-yl	379
	2,3-dimethylphenoxy	3-bromopyridin-5-yl	398
	2,3-dimethylphenoxy	4-methyl-1,2,3-thiadiazol-	340
		5-yl
	2,3-dimethylphenoxy	1-methyl-3-(2-(2-	378
		methyl)propyl)pyrazol-5-yl
	2,3-dimethylphenoxy	3-chlorobenzo[b]thiophen-	409
		2-yl
	2,3-dimethylphenoxy	4-chlorophenyl	353
	2,3-dimethylphenoxy	4-methyl-2-phenyl-1,2,3-	399
		triazol-5-yl
	2,3-dimethylphenoxy	benzo[b]thiophen-2-yl	374
	2,3-dimethylphenoxy	3,4-dimethylphenyl	346
	2,3-dimethylphenoxy	2-(phenoxy)pyridin-3-yl	411
	2,3-dimethylphenoxy	2-(methylthio)pyridin-3-yl	365
	2,3-dimethylphenoxy	5-methyl-3-phenylisoxazol-	399
		4-yl
	2,3-dimethylphenoxy	4-chloro-1,3-dimethyl	422
		pyrazolo[3,4-b]pyridin-3-
		yl
	2,3-dimethylphenoxy	2-chloro-6-methylpyridin-	368
		4-yl
	2,3-dimethylphenoxy	3,5-dimethylisoxazol-4-yl	337
	2,3-dimethylphenoxy	1-naphthyl	368
	2,3-dimethylphenoxy	2-fluorophenyl	336
	2,3-dimethylphenoxy	4-propylphenyl	360
	2,3-dimethylphenoxy	3-fluorophenyl	336
	2,3-dimethylphenoxy	2,6-difluorophenyl	354
	2,3-dimethylphenoxy	2-chlorophenyl	353
	2,3-dimethylphenoxy	3-(chloromethyl)phenyl	368
	2,3-dimethylphenoxy	4-(2-(2-methyl)propyl)	374
		phenyl
	2,3-dimethylphenoxy	3-chlorophenyl	353
	2,3-dimethylphenoxy	3,5-dimethoxyphenyl	378
	2,3-dimethylphenoxy	2,6-dichlorophenyl	387
	2,3-dimethylphenoxy	2,4-dichlorophenyl	387
	2,3-dimethylphenoxy	4-fluorophenyl	336
	2,3-dimethylphenoxy	4-butylphenyl	374
	2,3-dimethylphenoxy	2-methylphenyl	332
	2,3-dimethylphenoxy	phenyl	318
	2,3-dimethylphenoxy	4-ethylphenyl	346
	2,3-dimethylphenoxy	2,3-difluorophenyl	354
	2,3-dimethylphenoxy	2,6-dimethoxyphenyl	378
	2,3-dimethylphenoxy	3,4-difluorophenyl	354
	2,3-dimethylphenoxy	2,5-difluorophenyl	354
	2,3-dimethylphenoxy	4-ethoxyphenyl	362
	2,3-dimethylphenoxy	2,4,6-trichlorophenyl	422
	2,3-dimethylphenoxy	3-methylphenyl	332
	2,3-dimethylphenoxy	2-fluoro-5-	404
		(trifluoromethyl)phenyl
	2,3-dimethylphenoxy	3-methoxyphenyl	348
	2,3-dimethylphenoxy	2-bromophenyl	397
	2,3-dimethylphenoxy	4-bromophenyl	397
	2,3-dimethylphenoxy	4-fluoro-3-	404
		(trifluoromethyl)phenyl
	2,3-dimethylphenoxy	3-(trifluoromethoxy)phenyl	402
	2,3-dimethylphenoxy	9-fluorenon-4-yl	420
	2,3-dimethylphenoxy	isoxazol-5-yl	609
	2,3-dimethylphenoxy	benzofuroxan-5-yl	376
	2,3-dimethylphenoxy	2-chloropyrid-3-yl	354
	2,3-dimethylphenoxy	2-(4-	425
		methylphenoxy)pyridin-3-yl
	2,3-dimethylphenoxy	pyridin-4-yl	319
	2,3-dimethylphenoxy	anthraquinon-2-yl	448
	2,3-dimethylphenoxy	2-iodophenyl	444
	2,3-dimethylphenoxy	4-pentylphenyl	388
	2,3-dimethylphenoxy	2-(4-chlorophenylthio)	462
		pyridin-3-yl
	2,3-dimethylphenoxy	2,6-dimethylphenyl	346
	2,3-dimethylphenoxy	2,5-dimethoxyphenyl	378
	2,3-dimethylphenoxy	2,5-dichloropyridin-3-yl	388
	2,3-dimethylphenoxy	2-chloro-6-methoxypyridin-	384
		4-yl
	2,3-dimethylphenoxy	2,3-dichloropyridin-5-yl	388
	2,3-dimethylphenoxy	1-naphthyl	382
	2,3-dimethylphenoxy	2,4-dimethoxyphenyl	378
	2,3-dimethylphenoxy	3,5-bis(trifluoromethyl)	454
		phenyl
	2,3-dimethylphenoxy	2-(4-	446
		chlorophenoxy)pyridin-3-yl
	2,3-dimethylphenoxy	pentafluorophenyl	408
	3,5-(bis-2-	3,4-dimethoxyphenyl	434
	propyl)phenoxy
	3,5-(bis-2-	2-(trifluoromethyl)phenyl	442
	propyl)phenoxy
	3,5-(bis-2-	2,4-difluorophenyl	410
	propyl)phenoxy
	3,5-(bis-2-	3-(trifluoromethyl)phenyl	442
	propyl)phenoxy
	3,5-(bis-2-	2-naphthyl	425
	propyl)phenoxy
	3,5-(bis-2-	2-methoxyphenyl	404
	propyl)phenoxy
	3,5-(bis-2-	3,4,5-trimethylphenyl	465
	propyl)phenoxy
	3,5-(bis-2-	3,4-dichlorophenyl	443
	propyl)phenoxy
	3,5-(bis-2-	3-bromophenyl	453
	propyl)phenoxy
	3,5-(bis-2-	3-pyridyl	375
	propyl)phenoxy
	3,5-(bis-2-	2-ethoxynaphth-1-yl	469
	propyl)phenoxy
	3,5-(bis-2-	2,3-dichlorophenyl	443
	propyl)phenoxy
	3,5-(bis-2-	6-chloropyrid-3-yl	410
	propyl)phenoxy
	3,5-(bis-2-	4(trifluoromethoxy)phenyl	458
	propyl)phenoxy
	3,5-(bis-2-	2-fluoro-4-	460
	propyl)phenoxy	(trifluoromethyl)phenyl
	3,5-(bis-2-	3-bromothienyl	459
	propyl)phenoxy
	3,5-(bis-2-	2-acetoxyphenyl	432
	propyl)phenoxy
	3,5-(bis-2-	5-methylisoxazol-3-yl	379
	propyl)phenoxy
	3,5-(bis-2-	2-(phenylthio)pyrid-3-yl	484
	propyl)phenoxy
	3,5-(bis-2-	2-(trifluoromethoxy)phenyl	458
	propyl)phenoxy
	3,5-(bis-2-	1-phenyl-5-propylpyrazin-	483
	propyl)phenoxy	4-yl
	3,5-(bis-2-	2-ethoxyphenyl	418
	propyl)phenoxy
	3,5-(bis-2-	3-chlorothiophen-2-yl	415
	propyl)phenoxy
	3,5-(bis-2-	1-(2-(2-methyl)propyl)-3-	435
	propyl)phenoxy	methylpyrazol-5-yl
	3,5-(bis-2-	3,5-dichlorophenyl	443
	propyl)phenoxy
	3,5-(bis-2-	2-(propylthio)pyridin-3-yl	450
	propyl)phenoxy
	3,5-(bis-2-	2-(ethylthio)pyridin-3-yl	436
	propyl)phenoxy
	3,5-(bis-2-	3-bromopyridin-5-yl	454
	propyl)phenoxy
	3,5-(bis-2-	4-methyl-1,2,3-thiadiazol-	396
	propyl)phenoxy	5-yl
	3,5-(bis-2-	1-methyl-3-(2-(2-	435
	propyl)phenoxy	methyl)propyl)pyrazol-5-yl
	3,5-(bis-2-	3-chlorobenzo[b]thiophen-	465
	propyl)phenoxy	2-yl
	3,5-(bis-2-	4-chlorophenyl	409
	propyl)phenoxy
	3,5-(bis-2-	4-methyl-2-phenyl-1,2,3-	456
	propyl)phenoxy	triazol-5-yl
	3,5-(bis-2-	benzo[b]thiophen-2-yl	431
	propyl)phenoxy
	3,5-(bis-2-	3,4-dimethylphenyl	402
	propyl)phenoxy
	3,5-(bis-2-	2-(phenoxy)pyridin-3-yl	468
	propyl)phenoxy
	3,5-(bis-2-	2-(methylthio)pyridin-3-yl	422
	propyl)phenoxy
	3,5-(bis-2-	5-methyl-3-phenylisoxazol-	456
	propyl)phenoxy	4-yl
	3,5-(bis-2-	4-chloro-1,3-dimethyl	478
	propyl)phenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	3,5-(bis-2-	2-chloro-6-methylpyridin-	424
	propyl)phenoxy	4-yl
	3,5-(bis-2-	3,5-dimethylisoxazol-4-yl	393
	propyl)phenoxy
	3,5-(bis-2-	1-naphthyl	425
	propyl)phenoxy
	3,5-(bis-2-	2-fluorophenyl	392
	propyl)phenoxy
	3,5-(bis-2-	4-propylphenyl	417
	propyl)phenoxy
	3,5-(bis-2-	3-fluorophenyl	392
	propyl)phenoxy
	3,5-(bis-2-	2,6-difluorophenyl	410
	propyl)phenoxy
	3,5-(bis-2-	2-chlorophenyl	409
	propyl)phenoxy
	3,5-(bis-2-	3-(chloromethyl)phenyl	423
	propyl)phenoxy
	3,5-(bis-2-	4-(2-(2-methyl)propyl)	431
	propyl)phenoxy	phenyl
	3,5-(bis-2-	3-chlorophenyl	409
	propyl)phenoxy
	3 5-(bis-2-	3,5-dimethoxyphenyl	434
	propyl)phenoxy
	3,5-(bis-2-	2,6-dichlorophenyl	443
	propyl)phenoxy
	3,5-(bis-2-	2,4-dichlorophenyl	443
	propyl)phenoxy
	3,5-(bis-2-	4-fluorophenyl	392
	propyl)phenoxy
	3,5-(bis-2-	4-butylphenyl	431
	propyl)phenoxy
	3,5-(bis-2-	2-methylphenyl	388
	propyl)phenoxy
	3,5-(bis-2-	phenyl	374
	propyl)phenoxy
	3,5-(bis-2-	4-ethylphenyl	402
	propyl)phenoxy
	3,5-(bis-2-	2,3-difluorophenyl	410
	propyl)phenoxy
	3,5-(bis-2-	2,6-dimethoxyphenyl	434
	propyl)phenoxy
	3,5-(bis-2-	3,4-difluorophenyl	410
	propyl)phenoxy
	3,5-(bis-2-	2,5-difluorophenyl	410
	propyl)phenoxy
	3,5-(bis-2-	4-ethoxyphenyl	418
	propyl)phenoxy
	3,5-(bis-2-	2,4,6-trichlorophenyl	478
	propyl)phenoxy
	3,5-(bis-2-	3-methylphenyl	388
	propyl)phenoxy
	3,5-(bis-2-	2-fluoro-5-	460
	propyl)phenoxy	(trifluoromethyl)phenyl
	3,5-(bis-2-	3-methoxyphenyl	404
	propyl)phenoxy
	3,5-(bis-2-	2-bromophenyl	453
	propyl)phenoxy
	3,5-(bis-2-	4-bromophenyl	453
	propyl)phenoxy
	3,5-(bis-2-	4-fluoro-3-	460
	propyl)phenoxy	(trifluoromethyl)phenyl
	3,5-(bis-2-	3-(trifluoromethoxy)phenyl	458
	propyl)phenoxy
	3,5-(bis-2-	9-fluorenon-4-yl	477
	propyl)phenoxy
	3,5-(bis-2-	isoxazol-5-yl	365
	propyl)phenoxy
	3,5-(bis-2-	benzofuroxan-5-yl	432
	propyl)phenoxy
	3,5-(bis-2-	2-chloropyrid-3-yl	410
	propyl)phenoxy
	3,5-(bis-2-	2-(4-	482
	propyl)phenoxy	methylphenoxy)pyridin-3-yl
	3,5-(bis-2-	pyridin-4-yl	375
	propyl)phenoxy
	3,5-(bis-2-	anthraquinon-2-yl	505
	propyl)phenoxy
	3,5-(bis-2-	2-iodophenyl	500
	propyl)phenoxy
	3,5-(bis-2-	4-pentylphenyl	445
	propyl)phenoxy
	3,5-(bis-2-	2-(4-chlorophenylthio)	518
	propyl)phenoxy	pyridin-3-yl
	3,5-(bis-2-	2,6-dimethylphenyl	402
	propyl)phenoxy
	3,5-(bis-2-	2,5-dimethoxyphenyl	434
	propyl)phenoxy
	3,5-(bis-2-	2,5-dichloropyridin-3-yl	444
	propyl)phenoxy
	3,5-(bis-2-	2-chloro-6-methoxypyridin-	440
	propyl)phenoxy	4-yl
	3,5-(bis-2-	2,3-dichloropyridin-5-yl	444
	propyl)phenoxy
	3,5-(bis-2-	1-naphthyl	439
	propyl)phenoxy
	3,5-(bis-2-	2,4-dimethoxyphenyl	434
	propyl)phenoxy
	3,5-(bis-2-	3,5-bis(trifluoromethyl)	510
	propyl)phenoxy	phenyl
	3,5-(bis-2-	2-(4-	502
	propyl)phenoxy	chlorophenoxy)pyridin-3-yl
	3,5-(bis-2-	pentafluorophenyl	464
	propyl)phenoxy
	3-trifluoromethyl	3,4-dimethoxyphenyl	418
	phenoxy
	3-trifluoromethyl	2-(trifluoromethyl)phenyl	426
	phenoxy
	3-trifluoromethyl	2,4-difluorophenyl	394
	phenoxy
	3-trifluoromethyl	3-(trifluoromethyl)phenyl	426
	phenoxy
	3-trifluoromethyl	2-naphthyl	408
	phenoxy
	3-trifluoromethyl	2-methoxyphenyl	388
	phenoxy
	3-trifluoromethyl	3,4,5-trimethylphenyl	448
	phenoxy
	3-trifluoromethyl	3,4-dichlorophenyl	427
	phenoxy
	3-trifluoromethyl	3-bromophenyl	437
	phenoxy
	3-trifluoromethyl	3-pyridyl	359
	phenoxy
	3-trifluoromethyl	2-ethoxynaphth-1-yl	452
	phenoxy
	3-trifluoromethyl	2,3-dichlorophenyl	427
	phenoxy
	3-trifluoromethyl	6-chloropyrid-3-yl	394
	phenoxy
	3-trifluoromethyl	4-(trifluoromethoxy)phenyl	442
	phenoxy
	3-trifluoromethyl	2-fluoro-4-	444
	phenoxy	(trifluoromethyl)phenyl
	3-trifluoromethyl	3-bromothienyl	443
	phenoxy
	3-trifluoromethyl	2-acetoxyphenyl	416
	phenoxy
	3-trifluoromethyl	5-methylisoxazol-3-yl	363
	phenoxy
	3-trifluoromethyl	2-(phenylthio)pyrid-3-yl	467
	phenoxy
	3-trifluoromethyl	2-(trifluoromethoxy)phenyl	442
	phenoxy
	3-trifluoromethyl	1-phenyl-5-propylpyrazin-	466
	phenoxy	4-yl
	3-trifluoromethyl	2-ethoxyphenyl	402
	phenoxy
	3-trifluoromethyl	3-chlorothien-2-yl	399
	phenoxy
	3-trifluoromethyl	1 (2-(2-methyl)propyl)-3-	418
	phenoxy	methylpyrazol-5-yl
	3-trifluoromethyl	3,5-dichlorophenyl	427
	phenoxy
	3-trifluoromethyl	2-(propylthio)pyridin-3-yl	433
	phenoxy
	3-trifluoromethyl	2-(ethylthio)pyridin-3-yl	419
	phenoxy
	3-trifluoromethyl	3-bromopyridin-5-yl	438
	phenoxy
	3-trifluoromethyl	4-methyl-1,2,3-thiadiazol-	380
	phenoxy	5-yl
	3-trifluoromethyl	1-methyl-3-(2-(2-	418
	phenoxy	methyl)propyl)pyrazol-5-yl
	3-trifluoromethyl	3-chlorobenzo[b]thiophen-	449
	phenoxy	2-yl
	3-trifluoromethyl	4-chlorophenyl	393
	phenoxy
	3-trifluoromethyl	4-methyl-2-phenyl-1,2,3-	439
	phenoxy	triazol-5-yl
	3-trifluoromethyl	benzo[b]thiophen-2-yl	414
	phenoxy
	3-trifluoromethyl	3,4-dimethylphenyl	386
	phenoxy
	3-trifluoromethyl	2-(phenoxy)pyridin-3-yl	451
	phenoxy
	3-trifluoromethyl	2-(methylthio)pyridin-3-yl	405
	phenoxy
	3-trifluoromethyl	5-methyl-3-phenylisoxazol-	439
	phenoxy	4-yl
	3-trifluoromethyl	4-chloro-1,3-dimethyl	462
	phenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	3-trifluoromethyl	2-chloro-6-methylpyridin-	408
	phenoxy	4-yl
	3-trifluoromethyl	3,5-dimethylisoxazol-4-yl	377
	phenoxy
	3-trifluoromethyl	1-naphthyl	408
	phenoxy
	3-trifluoromethyl	2-fluorophenyl	476
	phenoxy
	3-trifluoromethyl	4-propylphenyl	400
	phenoxy
	3-trifluoromethyl	3-fluorophenyl	376
	phenoxy
	3-trifluoromethyl	2,6-difluorophenyl	394
	phenoxy
	3-trifluoromethyl	2-chlorophenyl	393
	phenoxy
	3-trifluoromethyl	3-(chloromethyl)phenyl	407
	phenoxy
	3-trifluoromethyl	4-(2-(2-methyl)propyl)	414
	phenoxy	phenyl
	3-trifluoromethyl	3-chlorophenyl	393
	phenoxy
	3-trifluoromethyl	3,5-dimethoxyphenyl	418
	phenoxy
	3-trifluoromethyl	2,6-dichlorophenyl	427
	phenoxy
	3-trifluoromethyl	2,4-dichlorophenyl	427
	phenoxy
	3-trifluoromethyl	4-fluorophenyl	376
	phenoxy
	3-trifluoromethyl	4-butylphenyl	414
	phenoxy
	3-trifluoromethyl	2-methylphenyl	372
	phenoxy
	3-trifluoromethyl	phenyl	358
	phenoxy
	3-trifluoromethyl	4-ethylphenyl	386
	phenoxy
	3-trifluoromethyl	2,3-difluorophenyl	394
	phenoxy
	3-trifluoromethyl	2,6-dimethoxyphenyl	418
	phenoxy
	3-trifluoromethyl	3,4-difluorophenyl	394
	phenoxy
	3-trifluoromethyl	2,5-difluorophenyl	394
	phenoxy
	3-trifluoromethyl	4-ethoxyphenyl	402
	phenoxy
	3-trifluoromethyl	2,4,6-trichlorophenyl	462
	phenoxy
	3-trifluoromethyl	3-methylphenyl	372
	phenoxy
	3-trifluoromethyl	2-fluoro-5-	444
	phenoxy	(trifluoromethyl)phenyl
	3-trifluoromethyl	3-methoxyphenyl	388
	phenoxy
	3-trifluoromethyl	2-bromophenyl	437
	phenoxy
	3-trifluoromethyl	4-bromophenyl	437
	phenoxy
	3-trifluoromethyl	4-fluoro-3-	444
	phenoxy	(trifluoromethyl)phenyl
	3-trifluoromethyl	3-(trifluoromethoxy)phenyl	442
	phenoxy
	3-trifluoromethyl	9-fluorenon-4-yl	460
	phenoxy
	3-trifluoromethyl	isoxazol-5-yl	349
	phenoxy
	3-trifluoromethyl	benzofuroxan-5-yl	416
	phenoxy
	3-trifluoromethyl	2-chloropyrid-3-yl	394
	phenoxy
	3-trifluoromethyl	2-(4-	465
	phenoxy	methylphenoxy)pyridin-3-yl
	3-trifluoromethyl	pyridin-4-yl	359
	phenoxy
	3-trifluoromethyl	anthraquinon-2-yl	488
	phenoxy
	3-trifluoromethyl	2-iodophenyl	484
	phenoxy
	3-trifluoromethyl	4-pentylphenyl	428
	phenoxy
	3-trifluoromethyl	2-(4-chlorophenylthio)	502
	phenoxy	pyridin-3-yl
	3-trifluoromethyl	2,6-dimethylphenyl	386
	phenoxy
	3-trifluoromethyl	2,5-dimethoxyphenyl	418
	phenoxy
	3-trifluoromethyl	2,5-dichloropyridin-3-yl	428
	phenoxy
	3-trifluoromethyl	2-chloro-6-methoxypyridin-	424
	phenoxy	4-yl
	3-trifluoromethyl	2,3-dichloropyridin-5-yl	428
	phenoxy
	3-trifluoromethyl	1-naphthyl	422
	phenoxy
	3-trifluoromethyl	2,4-dimethoxyphenyl	418
	phenoxy
	3-trifluoromethyl	3,5-	494
	phenoxy	bis(trifluoromethyl)phenyl
	3-trifluoromethyl	2-(4-	486
	phenoxy	chlorophenoxy)pyridin-3-yl
	3-trifluoromethyl	pentafluorophenyl	448
	phenoxy
	2,6-dichlorophenoxy	3,4-dimethoxyphenyl	419
	2,6-dichlorophenoxy	2-(trifluoromethyl)phenyl	427
	2,6-dichlorophenoxy	2,4-difluorophenyl	395
	2,6-dichlorophenoxy	3-(trifluoromethyl)phenyl	427
	2,6-dichlorophenoxy	2-naphthyl	409
	2,6-dichlorophenoxy	2-methoxyphenyl	389
	2,6-dichlorophenoxy	3,4,5-trimethylphenyl	449
	2,6-dichlorophenoxy	3,4-dichlorophenyl	428
	2,6-dichlorophenoxy	3-bromophenyl	438
	2,6-dichlorophenoxy	3-pyridyl	361
	2,6-dichlorophenoxy	2-ethoxynaphth-1-yl	453
	2,6-dichlorophenoxy	2,3-dichlorophenyl	428
	2,6-dichlorophenoxy	6-chloropyrid-3-yl	395
	2,6-dichlorophenoxy	4-(trifluoromethoxy)phenyl	443
	2,6-dichlorophenoxy	2-fluoro-4-	445
		(trifluoromethyl)phenyl
	2,6-dichlorophenoxy	3-bromothienyl	444
	2,6-dichlorophenoxy	2-acetoxyphenyl	417
	2,6-dichlorophenoxy	5-methylisoxazol-3-yl	364
	2,6-dichlorophenoxy	2-(phenylthio)pyrid-3-yl	468
	2,6-dichlorophenoxy	2-(trifluoromethoxy)phenyl	443
	2,6-dichlorophenoxy	1-phenyl-5-propylpyrazin-	467
		4-yl
	2,6-dichlorophenoxy	2-ethoxyphenyl	403
	2,6-dichlorophenoxy	3-chlorothien-2-yl	400
	2,6-dichlorophenoxy	1-(2-(2-methyl)propyl)-3-	419
		methylpyrazol-5-yl
	2,6-dichlorophenoxy	3,5-dichlorophenyl	428
	2,6-dichlorophenoxy	2-(propylthio)pyridin-3-yl	434
	2,6-dichlorophenoxy	2-(ethylthio)pyridin-3-yl	420
	2,6-dichlorophenoxy	3-bromopyridin-5-yl	439
	2,6-dichlorophenoxy	4-methyl-1,2,3-thiadiazol-	381
		5-yl
	2,6-dichlorophenoxy	1-methyl-3-(2-(2-	419
		methyl)propyl)pyrazol-5-yl
	2,6-dichlorophenoxy	3-chlorobenzo[b]thiophen-	450
		2-yl
	2,6-dichlorophenoxy	4-chlorophenyl	394
	2,6-dichlorophenoxy	4-methyl-2-phenyl-1,2,3-	440
		triazol-5-yl
	2,6-dichlorophenoxy	benzo[b]thiophen-2-yl	415
	2,6-dichlorophenoxy	3,4-dimethylphenyl	387
	2,6-dichlorophenoxy	2-(phenoxy)pyridin-3-yl	452
	2,6-dichlorophenoxy	2-(methylthio)pyridin-3-yl	406
	2,6-dichlorophenoxy	5-methyl-3-phenylisoxazol-	440
		4-yl
	2,6-dichlorophenoxy	4-chloro-1,3-dimethyl	463
		pyrazolo[3,4-b]pyridin-3-
		yl
	2,6-dichlorophenoxy	2-chloro-6-methylpyridin-	409
		4-yl
	2,6-dichlorophenoxy	3,5-dimethylisoxazol-4-yl	378
	2,6-dichlorophenoxy	1-naphthyl	409
	2,6-dichlorophenoxy	2-fluorophenyl	377
	2,6-dichlorophenoxy	4-propylphenyl	401
	2,6-dichlorophenoxy	3-fluorophenyl	377
	2,6-dichlorophenoxy	2,6-difluorophenyl	395
	2,6-dichlorophenoxy	2-chlorophenyl	394
	2,6-dichlorophenoxy	3-(chloromethyl)phenyl	408
	2,6-dichlorophenoxy	4-(2-(2-methyl)propyl)	415
		phenyl
	2,6-dichlorophenoxy	3-chlorophenyl	694
	2,6-dichlorophenoxy	3,5-dimethoxyphenyl	419
	2,6-dichlorophenoxy	2,6-dichlorophenyl	428
	2,6-dichlorophenoxy	2,4-dichlorophenyl	428
	2,6-dichlorophenoxy	4-fluorophenyl	377
	2,6-dichlorophenoxy	4-butylphenyl	415
	2,6-dichlorophenoxy	2-methylphenyl	373
	2,6-dichlorophenoxy	phenyl	359
	2,6-dichlorophenoxy	4-ethylphenyl	387
	2,6-dichlorophenoxy	2,3-difluorophenyl	395
	2,6-dichlorophenoxy	2,6-dimethoxyphenyl	419
	2,6-dichlorophenoxy	3,4-difluorophenyl	395
	2,6-dichlorophenoxy	2,5-difluorophenyl	395
	2,6-dichlorophenoxy	4-ethoxyphenyl	403
	2,6-dichlorophenoxy	2,4,6-trichlorophenyl	463
	2,6-dichlorophenoxy	3-methylphenyl	373
	2,6-dichlorophenoxy	2-fluoro-5-	445
		(trifluoromethyl)phenyl
	2,6-dichlorophenoxy	3-methoxyphenyl	389
	2,6-dichlorophenoxy	2-bromophenyl	438
	2,6-dichlorophenoxy	4-bromophenyl	438
	2,6-dichlorophenoxy	4-fluoro-3-	445
		(trifluoromethyl)phenyl
	2,6-dichlorophenoxy	3-(trifluoromethoxy)phenyl	443
	2,6-dichlorophenoxy	9-fluorenon-4-yl	461
	2,6-dichlorophenoxy	isoxazol-5-yl	350
	2,6-dichlorophenoxy	benzofuroxan-5-yl	417
	2,6-dichlorophenoxy	2-chloropyrid-3-yl	395
	2,6-dichlorophenoxy	2-(4-	466
		methylphenoxy)pyridin-3-yl
	2,6-dichlorophenoxy	pyridin-4-yl	360
	2,6-dichlorophenoxy	anthraquinon-2-yl	489
	2,6-dichlorophenoxy	2-iodophenyl	485
	2,6-dichlorophenoxy	4-pentylphenyl	429
	2,6-dichlorophenoxy	2-(4-chlorophenylthio)	503
		pyridin-3-yl
	2,6-dichlorophenoxy	2,6-dimethylphenyl	387
	2,6-dichlorophenoxy	2,5-dimethoxyphenyl	419
	2,6-dichlorophenoxy	2,5-dichloropyridin-3-yl	429
	2,6-dichlorophenoxy	2-chloro-6-methoxypyridin-	425
		4-yl
	2,6-dichlorophenoxy	2,3-dichloropyridin-5-yl	429
	2,6-dichlorophenoxy	1-naphthyl	413
	2,6-dichlorophenoxy	2,4-dimethoxyphenyl	419
	2,6-dichlorophenoxy	3,5-	495
		bis(trifluoromethyl)phenyl
	2,6-dichlorophenoxy	2-(4-	487
		chlorophenoxy)pyridin-3-yl
	2,6-dichlorophenoxy	pentafluorophenyl	449
	2,4-dichlorophenoxy	3,4-dimethoxyphenyl	419
	2,4-dichlorophenoxy	2-(trifluoromethyl)phenyl	427
	2,4-dichlorophenoxy	2,4-difluorophenyl	395
	2,4-dichlorophenoxy	3-(trifluoromethyl)phenyl	427
	2,4-dichlorophenoxy	2-naphthyl	409
	2,4-dichlorophenoxy	2-methoxyphenyl	389
	2,4-dichlorophenoxy	3,4,5-trimethylphenyl	449
	2,4-dichlorophenoxy	3,4-dichlorophenyl	428
	2,4-dichlorophenoxy	3-bromophenyl	438
	2,4-dichlorophenoxy	3-pyridyl	361
	2,4-dichlorophenoxy	2-ethoxynaphth-1-yl	453
	2,4-dichlorophenoxy	2,3-dichlorophenyl	428
	2,4-dichlorophenoxy	6-chloropyrid-3-yl	395
	2,4-dichlorophenoxy	4-(trifluoromethoxy)phenyl	443
	2,4-dichlorophenoxy	2-fluoro-4-	445
		(trifluoromethyl)phenyl
	2,4-dichlorophenoxy	3-bromothienyl	444
	2,4-dichlorophenoxy	2-acetoxyphenyl	417
	2,4-dichlorophenoxy	5-methylisoxazol-3-yl	364
	2,4-dichlorophenoxy	2-(phenylthio)pyrid-3-yl	468
	2,4-dichlorophenoxy	2-(trifluoromethoxy)phenyl	443
	2,4-dichlorophenoxy	1-phenyl-5-propylpyrazin-	467
		4-yl
	2,4-dichlorophenoxy	2-ethoxyphenyl	403
	2,4-dichlorophenoxy	3-chlorothien-2-yl	400
	2,4-dichlorophenoxy	1-(2-(2-methyl)propyl)-3-	419
		methylpyrazol-5-yl
	2,4-dichlorophenoxy	3,5-dichlorophenyl	428
	2,4-dichlorophenoxy	2-(propylthio)pyridin-3-yl	434
	2,4-dichlorophenoxy	2-(ethylthio)pyridin-3-yl	420
	2,4-dichlorophenoxy	3-bromopyridin-5-yl	439
	2,4-dichlorophenoxy	4-methyl-1,2,3-thiadiazol-	381
		5-yl
	2,4-dichlorophenoxy	1-methyl-3-(2-(2-	419
		methyl)propyl)pyrazol-5-yl
	2,4-dichlorophenoxy	3-chlorobenzo[b]thiophen-	450
		2-yl
	2,4-dichlorophenoxy	4-chlorophenyl	394
	2,4-dichlorophenoxy	4-methyl-2-phenyl-1,2,3-	440
		triazol-5-yl
	2,4-dichlorophenoxy	benzo[b]thiophen-2-yl	415
	2,4-dichlorophenoxy	3,4-dimethylphenyl	387
	2,4-dichlorophenoxy	2-(phenoxy)pyridin-3-yl	452
	2,4-dichlorophenoxy	2-(methylthio)pyridin-3-yl	406
	2,4-dichlorophenoxy	5-methyl-3-phenylisoxazol-	440
		4-yl
	2,4-dichlorophenoxy	4-chloro-1,3-dimethyl	463
		pyrazolo[3,4-b]pyridin-3-
		yl
	2,4-dichlorophenoxy	2-chloro-6-methylpyridin-	409
		4-yl
	2,4-dichlorophenoxy	3,5-dimethylisoxazol-4-yl	378
	2,4-dichlorophenoxy	1-naphthyl	409
	2,4-dichlorophenoxy	2-fluorophenyl	377
	2,4-dichlorophenoxy	4-propylphenyl	401
	2,4-dichlorophenoxy	3-fluorophenyl	377
	2,4-dichlorophenoxy	2,6-difluorophenyl	395
	2,4-dichlorophenoxy	2-chlorophenyl	394
	2,4-dichlorophenoxy	3-(chloromethyl)phenyl	408
	2,4-dichlorophenoxy	4-(2-(2-	415
		methyl)propyl)phenyl
	2,4-dichlorophenoxy	3-chlorophenyl	694
	2,4-dichlorophenoxy	3,5-dimethoxyphenyl	419
	2,4-dichlorophenoxy	2,6-dichlorophenyl	428
	2,4-dichlorophenoxy	2,4-dichlorophenyl	428
	2,4-dichlorophenoxy	4-fluorophenyl	377
	2 4-dichlorophenoxy	4-butylphenyl	415
	2,4-dichlorophenoxy	2-methylphenyl	373
	2,4-dichlorophenoxy	phenyl	359
	2,4-dichlorophenoxy	4-ethylphenyl	387
	2,4-dichlorophenoxy	2,3-difluorophenyl	395
	2,4-dichlorophenoxy	2,6-dimethoxyphenyl	419
	2,4-dichlorophenoxy	3,4-difluorophenyl	395
	2,4-dichlorophenoxy	2,5-difluorophenyl	395
	2,4-dichlorophenoxy	4-ethoxyphenyl	403
	2,4-dichlorophenoxy	2,4,6-trichlorophenyl	463
	2,4-dichlorophenoxy	3-methylphenyl	373
	2,4-dichlorophenoxy	2-fluoro-5-	445
		(trifluoromethyl)phenyl
	2,4-dichlorophenoxy	3-methoxyphenyl	389
	2,4-dichlorophenoxy	2-bromophenyl	438
	2,4-dichlorophenoxy	4-bromophenyl	438
	2,4-dichlorophenoxy	4-fluoro-3-	445
		(trifluoromethyl)phenyl
	2,4-dichlorophenoxy	3-(trifluoromethoxy)phenyl	443
	2,4-dichlorophenoxy	9-fluorenon-4-yl	461
	2,4-dichlorophenoxy	isoxazol-5-yl	350
	2,4-dichlorophenoxy	benzofuroxan-5-yl	417
	2,4-dichlorophenoxy	2-chloropyrid-3-yl	395
	2,4-dichlorophenoxy	2-(4-	466
		methylphenoxy)pyridin-3-yl
	2,4-dichlorophenoxy	pyridin-4-yl	360
	2,4-dichlorophenoxy	anthraquinon-2-yl	489
	2,4-dichlorophenoxy	2-iodophenyl	485
	2,4-dichlorophenoxy	4-pentylphenyl	429
	2,4-dichlorophenoxy	2-(4-chlorophenylthio)	503
		pyridin-3-yl
	2,4-dichlorophenoxy	2,6-dimethylphenyl	387
	2,4-dichlorophenoxy	2,5-dimethoxyphenyl	419
	2,4-dichlorophenoxy	2,5-dichloropyridin-3-yl	429
	2,4-dichlorophenoxy	2-chloro-6-methoxypyridin-	425
		4-yl
	2,4-dichlorophenoxy	2,3-dichloropyridin-5-yl	429
	2,4-dichlorophenoxy	1-naphthyl	413
	2,4-dichlorophenoxy	2,4-dimethoxyphenyl	419
	2,4-dichlorophenoxy	3,5-	495
		bis(trifluoromethyl)phenyl
	2,4-dichlorophenoxy	2-(4-	487
		chlorophenoxy)pyridin-3-yl
	2,4-dichlorophenoxy	pentafluorophenyl	449
	4-chloro-3-	3,4-dimethoxyphenyl	319
	methylphenoxy
	4-chloro-3-	2-(trifluoromethyl)phenyl	407
	methylphenoxy
	4-chloro-3-	2,4-difluorophenyl	375
	methylphenoxy
	4-chloro-3-	3-(trifluoromethyl)phenyl	407
	methylphenoxy
	4-chloro-3-	2-naphthyl	389
	methylphenoxy
	4-chloro-3-	2-methoxyphenyl	369
	methylphenoxy
	4-chloro-3-	3,4,5-trimethylphenyl	429
	methylphenoxy
	4-chloro-3-	3,4-dichlorophenyl	408
	methylphenoxy
	4-chloro-3-	3-bromophenyl	418
	methylphenoxy
	4-chloro-3-	3-pyridyl	340
	methylphenoxy
	4-chloro-3-	2-ethoxynaphth-1-yl	433
	methylphenoxy
	4-chloro-3-	2,3-dichlorophenyl	408
	methylphenoxy
	4-chloro-3-	6-chloropyrid-3-yl	374
	methylphenoxy
	4-chloro-3-	4-(trifluoromethoxy)phenyl	423
	methylphenoxy
	4-chloro-3-	2-fluoro-4-	425
	methylphenoxy	(trifluoromethyl)phenyl
	4-chloro-3-	3-bromothienyl	424
	methylphenoxy
	4-chloro-3-	2-acetoxyphenyl	397
	methylphenoxy
	4-chloro-3-	5-methylisoxazol-3-yl	344
	methylphenoxy
	4-chloro-3-	2-(phenylthio)pyrid-3-yl	448
	methylphenoxy
	4-chloro-3-	2-(trifluoromethoxy)phenyl	423
	methylphenoxy
	4-chloro-3-	1-phenyl-5-propylpyrazin-	447
	methylphenoxy	4-yl
	4-chloro-3-	2-ethoxyphenyl	383
	methylphenoxy
	4-chloro-3-	3-chlorothien-2-yl	379
	methylphenoxy
	4-chloro-3-	1-(2-(2-methyl)propyl)-3-	399
	methylphenoxy	methylpyrazol-5-yl
	4-chloro-3-	3,5-dichlorophenyl	408
	methylphenoxy
	4-chloro-3-	2-(propylthio)pyridin-3-yl	414
	methylphenoxy
	4-chloro-3-	2-(ethylthio)pyridin-3-yl	400
	methylphenoxy
	4-chloro-3-	3-bromopyridin-5-yl	419
	methylphenoxy
	4-chloro-3-	4-methyl-1,2,3-thiadiazol-	361
	methylphenoxy	5-yl
	4-chloro-3-	1-methyl-3-(2-(2-	399
	methylphenoxy	methyl)propyl)pyrazol-5-yl
	4-chloro-3-	3-chlorobenzo[b]thiophen-	429
	methylphenoxy	2-yl
	4-chloro-3-	4-chlorophenyl	373
	methylphenoxy
	4-chloro-3-	4-methyl-2-phenyl-1,2,3-	420
	methylphenoxy	triazol-5-yl
	4-chloro-3-	benzo[b]thiophen-2-yl	395
	methylphenoxy
	4-chloro-3-	3,4-dimethylphenyl	367
	methylphenoxy
	4-chloro-3-	2-(phenoxy)pyridin-3-yl	432
	methylphenoxy
	4-chloro-3-	2-(methylthio)pyridin-3-yl	386
	methylphenoxy
	4-chloro-3-	5-methyl-3-phenylisoxazol-	420
	methylphenoxy	4-yl
	4-chloro-3-	4-chloro-1,3-dimethyl	442
	methylphenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	4-chloro-3-	2-chloro-6-methylpyridin-	388
	methylphenoxy	4-yl
	4-chloro-3-	3,5-dimethylisoxazol-4-yl	358
	methylphenoxy
	4-chloro-3-	1-naphthyl	389
	methylphenoxy
	4-chloro-3-	2-fluorophenyl	357
	methylphenoxy
	4-chloro-3-	4-propylphenyl	381
	methylphenoxy
	4-chloro-3-	4-(trifluoromethyl)phenyl	407
	methylphenoxy
	4-chloro-3-	3-fluorophenyl	357
	methylphenoxy
	4-chloro-3-	2,6-difluorophenyl	375
	methylphenoxy
	4-chloro-3-	2-chlorophenyl	373
	methylphenoxy
	4-chloro-3-	3-(chloromethyl)phenyl	387
	methylphenoxy
	4-chloro-3-	4-(2-(2-	395
	methylphenoxy	methyl)propyl)phenyl
	4-chloro-3-	3-chlorophenyl	373
	methylphenoxy
	4-chloro-3-	3,5-dimethoxyphenyl	399
	methylphenoxy
	4-chloro-3-	2,6-dichlorophenyl	408
	methylphenoxy
	4-chloro-3-	2,4-dichlorophenyl	408
	methylphenoxy
	4-chloro-3-	4-fluorophenyl	357
	methylphenoxy
	4-chloro-3-	4-butylphenyl	395
	methylphenoxy
	4-chloro-3-	2-methylphenyl	353
	methylphenoxy
	4-chloro-3-	phenyl	339
	methylphenoxy
	4-chloro-3-	4-ethylphenyl	367
	methylphenoxy
	4-chloro-3-	2,3-difluorophenyl	375
	methylphenoxy
	4-chloro-3-	2,6-dimethoxyphenyl	399
	methylphenoxy
	4-chloro-3-	3,4-difluorophenyl	375
	methylphenoxy
	4-chloro-3-	2,5-difluorophenyl	375
	methylphenoxy
	4-chloro-3-	4-ethoxyphenyl	383
	methylphenoxy
	4-chloro-3-	2,4,6-trichlorophenyl	442
	methylphenoxy
	4-chloro-3-	3-methylphenyl	353
	methylphenoxy
	4-chloro-3-	2-fluoro-5-	425
	methylphenoxy	(trifluoromethyl)phenyl
	4-chloro-3-	3-methoxyphenyl	369
	methylphenoxy
	4-chloro-3-	2-bromophenyl	418
	methylphenoxy
	4-chloro-3-	4-bromophenyl	418
	methylphenoxy
	4-chloro-3-	4-fluoro-3-	425
	methylphenoxy	(trifluoromethyl)phenyl
	4-chloro-3-	3-(trifluoromethoxy)phenyl	423
	methylphenoxy
	4-chloro-3-	9-fluorenon-4-yl	441
	methylphenoxy
	4-chloro-3-	isoxazol-5-yl	330
	methylphenoxy
	4-chloro-3-	benzofuroxan-5-yl	397
	methylphenoxy
	4-chloro-3-	2-chloropyrid-3-yl	374
	methylphenoxy
	4-chloro-3-	2-(4-	446
	methylphenoxy	methylphenoxy)pyridin-3-yl
	4-chloro-3-	pyridin-4-yl	340
	methylphenoxy
	4-chloro-3-	anthraquinon-2-yl	469
	methylphenoxy
	4-chloro-3-	2-iodophenyl	465
	methylphenoxy
	4-chloro-3-	4-pentylphenyl	409
	methylphenoxy
	4-chloro-3-	2-(4-chlorophenylthio)	482
	methylphenoxy	pyridin-3-yl
	4-chloro-3-	2,6-dimethylphenyl	367
	methylphenoxy
	4-chloro-3-	2,5-dimethoxyphenyl	399
	methylphenoxy
	4-chloro-3-	2,5-dichloropyridin-3-yl	409
	methylphenoxy
	4-chloro-3-	2-chloro-6-methoxypyridin	404
	methylphenoxy	4-yl
	4-chloro-3-	2,3-dichloropyridin-5-yl	409
	methylphenoxy
	4-chloro-3-	1-naphthyl	403
	methylphenoxy
	4-chloro-3-	2,4-dimethoxyphenyl	399
	methylphenoxy
	4-chloro-3-	3,5-	475
	methylphenoxy	bis(trifluoromethyl)phenyl
	4-chloro-3-	2-(4-	466
	methylphenoxy	chlorophenoxy)pyridin-3-yl
	4-chloro-3-	pentafluorophenyl	429
	methylphenoxy
	4-chloro-2-	3,4-dimethoxyphenyl	467
	cyclohexylphenoxy
	4-chloro-2-	2-(trifluoromethyl)phenyl	475
	cyclohexylphenoxy
	4-chloro-2-	2,4-difluorophenyl	443
	cyclohexylphenoxy
	4-chloro-2-	3-(trifluoromethyl)phenyl	475
	cyclohexylphenoxy
	4-chloro-2-	2-naphthyl	457
	cyclohexylphenoxy
	4-chloro-2-	2-methoxyphenyl	437
	cyclohexylphenoxy
	4-chloro-2-	3,4,5-trimethylphenyl	497
	cyclohexylphenoxy
	4-chloro-2-	3,4-dichlorophenyl	176
	cyclohexylphenoxy
	4-chloro-2-	3-bromophenyl	486
	cyclohexylphenoxy
	4-chloro-2-	3-pyridyl	408
	cyclohexylphenoxy
	4-chloro-2-	2-ethoxynaphth-1-yl	501
	cyclohexylphenoxy
	4-chloro-2-	2,3-dichlorophenyl	476
	cyclohexylphenoxy
	4-chloro-2-	6-chloropyrid-3-yl	442
	cyclohexylphenoxy
	4-chloro-2-	4-(trifluoromethoxy)phenyl	491
	cyclohexylphenoxy
	4-chloro-2-	2-fluoro-4-	493
	cyclohexylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2-	3-bromothienyl	492
	cyclohexylphenoxy
	4-chloro-2-	2-acetoxyphenyl	465
	cyclohexylphenoxy
	4-chloro-2-	5-methylisoxazol-3-yl	412
	cyclohexylphenoxy
	4-chloro-2-	2-(phenylthio)pyrid-3-yl	516
	cyclohexylphenoxy
	4-chloro-2-	2-(trifluoromethoxy)phenyl	491
	cyclohexylphenoxy
	4-chloro-2-	1-phenyl-5-propylpyrazin-	515
	cyclohexylphenoxy	4-yl
	4-chloro-2-	2-ethoxyphenyl	451
	cyclohexylphenoxy
	4-chloro-2-	3-chlorothien-2-yl	447
	cyclohexylphenoxy
	4-chloro-2-	1-(2-(2-methyl)propyl)-3-	467
	cyclohexylphenoxy	methylpyrazol-5-yl
	4-chloro-2-	3,5-dichlorophenyl	476
	cyclohexylphenoxy
	4-chloro-2-	2-(propylthio)pyridin-3-yl	482
	cyclohexylphenoxy
	4-chloro-2-	2-(ethylthio)pyridin-3-yl	468
	cyclohexylphenoxy
	4-chloro-2-	3-bromopyridin-5-yl	487
	cyclohexylphenoxy
	4-chloro-2-	4-methyl-1,2,3-thiadiazol-	429
	cyclohexylphenoxy	5-yl
	4-chloro-2-	1-methyl-3-(2-(2-	467
	cyclohexylphenoxy	methyl)propyl)pyrazol-5-yl
	4-chloro-2-	3-chlorobenzo[b]thiophen-	497
	cyclohexylphenoxy	2-yl
	4-chloro-2-	4-chlorophenyl	441
	cyclohexylphenoxy
	4-chloro-2-	4-methyl-2-phenyl-1,2,3-	488
	cyclohexylphenoxy	triazol-5-yl
	4-chloro-2-	benzo[b]thiophen-2-yl	463
	cyclohexylphenoxy
	4-chloro-2-	3,4-dimethylphenyl	435
	cyclohexylphenoxy
	4-chloro-2-	2-(phenoxy)pyridin-3-yl	500
	cyclohexylphenoxy
	4-chloro-2-	2-(methylthio)pyridin-3-yl	454
	cyclohexylphenoxy
	4-chloro-2-	5-methyl-3-phenylisoxazol-	488
	cyclohexylphenoxy	4-yl
	4-chloro-2-	4-chloro-1,3-dimethyl	510
	cyclohexylphenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	4-chloro-2-	2-chloro-6-methylpyridin-	456
	cyclohexylphenoxy	4-yl
	4-chloro-2-	3,5-dimethylisoxazol-4-yl	426
	cyclohexylphenoxy
	4-chloro-2-	1-naphthyl	457
	cyclohexylphenoxy
	4-chloro-2-	2-fluorophenyl	425
	cyclohexylphenoxy
	4-chloro-2-	4-propylphenyl	449
	cyclohexylphenoxy
	4-chloro-2-	3-fluorophenyl	425
	cyclohexylphenoxy
	4-chloro-2-	2,6-difluorophenyl	443
	cyclohexylphenoxy
	4-chloro-2-	2-chlorophenyl	441
	cyclohexylphenoxy
	4-chloro-2-	3-(chloromethyl)phenyl	455
	cyclohexylphenoxy
	4-chloro-2-	4-(2-(2-	463
	cyclohexylphenoxy	methyl)propyl)phenyl
	4-chloro-2-	3-chlorophenyl	441
	cyclohexylphenoxy
	4-chloro-2-	3,5-dimethoxyphenyl	467
	cyclohexylphenoxy
	4-chloro-2-	2,6-dichlorophenyl	476
	cyclohexylphenoxy
	4-chloro-2-	2,4-dichlorophenyl	476
	cyclohexylphenoxy
	4-chloro-2-	4-fluorophenyl	425
	cyclohexylphenoxy
	4-chloro-2-	4-butylphenyl	463
	cyclohexylphenoxy
	4-chloro-2-	2-methylphenyl	421
	cyclohexylphenoxy
	4-chloro-2-	phenyl	407
	cyclohexylphenoxy
	4-chloro-2-	4-ethylphenyl	435
	cyclohexylphenoxy
	4-chloro-2-	2,3-difluorophenyl	443
	cyclohexylphenoxy
	4-chloro-2-	2,6-dimethoxyphenyl	467
	cyclohexylphenoxy
	4-chloro-2-	3,4-difluorophenyl	443
	cyclohexylphenoxy
	4-chloro-2-	2,5-difluorophenyl	443
	cyclohexylphenoxy
	4-chloro-2-	4-ethoxyphenyl	451
	cyclohexylphenoxy
	4-chloro-2-	2,4,6-trichlorophenyl	510
	cyclohexylphenoxy
	4-chloro-2-	3-methylphenyl	421
	cyclohexylphenoxy
	4-chloro-2-	2-fluoro-5-	493
	cyclohexylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2-	3-methoxyphenyl	437
	cyclohexylphenoxy
	4-chloro-2-	2-bromophenyl	486
	cyclohexylphenoxy
	4-chloro-2-	4-bromophenyl	486
	cyclohexylphenoxy
	4-chloro-2-	4-fluoro-3-	493
	cyclohexylphenoxy	(trifluoromethyl)phenyl
	4-chloro-2-	3-(trifluoromethoxy)phenyl	491
	cyclohexylphenoxy
	4-chloro-2-	9-fluorenon-4-yl	503
	cyclohexylphenoxy
	4-chloro-2-	isoxazol-5-yl	398
	cyclohexylphenoxy
	4-chloro-2-	benzofuroxan-5-yl	465
	cyclohexylphenoxy
	4-chloro-2-	2-chloropyrid-3-yl	442
	cyclohexylphenoxy
	4-chloro-2-	2-(4-	514
	cyclohexylphenoxy	methylphenoxy)pyridin-3-yl
	4-chloro-2-	pyridin-4-yl	408
	cyclohexylphenoxy
	4-chloro-2-	anthraquinon-2-yl	537
	cyclohexylphenoxy
	4-chloro-2-	2-iodophenyl	533
	cyclohexylphenoxy
	4-chloro-2-	4-pentylphenyl	477
	cyclohexylphenoxy
	4-chloro-2-	2-(4-chlorophenylthio)	550
	cyclohexylphenoxy	pyridin-3-yl
	4-chloro-2-	2,6-dimethylphenyl	435
	cyclohexylphenoxy
	4-chloro-2-	2,5-dimethoxyphenyl	467
	cyclohexylphenoxy
	4-chloro-2-	2,5-dichloropyridin-3-yl	477
	cyclohexylphenoxy
	4-chloro-2-	2-chloro-6-methoxypyridin	472
	cyclohexylphenoxy	4-yl
	4-chloro-2-	2,3-dichloropyridin-5-yl	477
	cyclohexylphenoxy
	4-chloro-2-	1-naphthyl	471
	cyclohexylphenoxy
	4-chloro-2-	2,4-dimethoxyphenyl	467
	cyclohexylphenoxy
	4-chloro-2-	3,5-	546
	cyclohexylphenoxy	bis(trifluoromethyl)phenyl
	4-chloro-2-	2-(4-	534
	cyclohexylphenoxy	chlorophenoxy)pyridin-3-yl
	4-chloro-2-	pentafluorophenyl	497
	cyclohexylphenoxy
	4-chloro-3,5-	3,4-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-3,5-	2-(trifluoromethyl)phenyl	421
	dimethylphenoxy
	4-chloro-3,5-	2,4-difluorophenyl	389
	dimethylphenoxy
	4-chloro-3,5-	3-(trifluoromethyl)phenyl	421
	dimethylphenoxy
	4-chloro-3,5-	2-naphthyl	403
	dimethylphenoxy
	4-chloro-3,5-	2-methoxyphenyl	484
	dimethylphenoxy
	4-chloro-3,5-	3,4,5-trimethylphenyl	443
	dimethylphenoxy
	4-chloro-3,5-	3,4-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-3,5-	3-bromophenyl	432
	dimethylphenoxy
	4-chloro-3,5-	3-pyridyl	354
	dimethylphenoxy
	4-chloro-3,5-	2-ethoxynaphth-1-yl	447
	dimethylphenoxy
	4-chloro-3,5-	2,3-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-3,5-	6-chloropyrid-3-yl	388
	dimethylphenoxy
	4-chloro-3,5-	4-(trifluoromethoxy)phenyl	437
	dimethylphenoxy
	4-chloro-3,5-	2-fluoro-4-	439
	dimethylphenoxy	(trifluoromethyl)phenyl
	4-chloro-3,5-	3-bromothienyl	438
	dimethylphenoxy
	4-chloro-3,5-	2-acetoxyphenyl	411
	dimethylphenoxy
	4-chloro-3,5-	5-methylisoxazol-3-yl	358
	dimethylphenoxy
	4-chloro-3,5-	2-(phenylthio)pyrid-3-yl	462
	dimethylphenoxy
	4-chloro-3,5-	2-(trifluoromethoxy)phenyl	437
	dimethylphenoxy
	4-chloro-3,5-	1-phenyl-5-propylpyrazin-	461
	dimethylphenoxy	4-yl
	4-chloro-3,5-	2-ethoxyphenyl	397
	dimethylphenoxy
	4-chloro-3,5-	3-chlorothien-2-yl	393
	dimethylphenoxy
	4-chloro-3,5-	1-(2-(2-methyl)propyl)-3-	413
	dimethylphenoxy	methylpyrazol-5-yl
	4-chloro-3,5-	3,5-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-3,5-	2-(propylthio)pyridin-3-yl	428
	dimethylphenoxy
	4-chloro-3,5-	2-(ethylthio)pyridin-3-yl	414
	dimethylphenoxy
	4-chloro-3,5-	3-bromopyridin-5-yl	433
	dimethylphenoxy
	4-chloro-3,5-	4-methyl-1,2,3-thiadiazol-	375
	dimethylphenoxy	5-yl
	4-chloro-3,5-	1-methyl-3-(2-(2-	413
	dimethylphenoxy	methyl)propyl)pyrazol-5-yl
	4-chloro-3,5-	3-chlorobenzo[b]thiophen	443
	dimethylphenoxy	2-yl
	4-chloro-3,5-	4-chlorophenyl	387
	dimethylphenoxy
	4-chloro-3,5-	4-methyl-2-phenyl-1,2,3-	434
	dimethylphenoxy	triazol-5-yl
	4-chloro-3,5-	benzo[b]thiophen-2-yl	409
	dimethylphenoxy
	4-chloro-3,5-	3,4-dimethylphenyl	381
	dimethylphenoxy
	4-chloro-3,5-	2-(phenoxy)pyridin-3-yl	446
	dimethylphenoxy
	4-chloro-3,5-	2-(methylthio)pyridin-3-yl	400
	dimethylphenoxy
	4-chloro-3,5-	5-methyl-3-phenylisoxazol-	434
	dimethylphenoxy	4-yl
	4-chloro-3,5-	4-chloro-1,3-dimethyl	456
	dimethylphenoxy	pyrazolo[3,4-b]pyridin-3-
		yl
	4-chloro-3,5-	2-chloro-6-methylpyridin	402
	dimethylphenoxy	4-yl
	4-chloro-3,5-	3,5-dimethylisoxazol-4-yl	372
	dimethylphenoxy
	4-chloro-3,5-	1-naphthyl	403
	dimethylphenoxy
	4-chloro-3,5-	2-fluorophenyl	371
	dimethylphenoxy
	4-chloro-3,5-	4-propylphenyl	395
	dimethylphenoxy
	4-chloro-3,5-	3-fluorophenyl	371
	dimethylphenoxy
	4-chloro-3,5-	2,6-difluorophenyl	389
	dimethylphenoxy
	4-chloro-3,5-	2-chlorophenyl	387
	dimethylphenoxy
	4-chloro-3,5-	3-(chloromethyl)phenyl	401
	dimethylphenoxy
	4-chloro-3,5-	4-(2-(2-	409
	dimethylphenoxy	methyl)propyl)phenyl
	4-chloro-3,5-	3-chlorophenyl	387
	dimethylphenoxy
	4-chloro-3,5-	3,5-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-3,5-	2,6-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-3,5-	2,4-dichlorophenyl	422
	dimethylphenoxy
	4-chloro-3,5-	4-fluorophenyl	371
	dimethylphenoxy
	4-chloro-3,5-	4-butylphenyl	409
	dimethylphenoxy
	4-chloro-3,5-	2-methylphenyl	367
	dimethylphenoxy
	4-chloro-3,5-	phenyl	353
	dimethylphenoxy
	4-chloro-3,5-	4-ethylphenyl	381
	dimethylphenoxy
	4-chloro-3,5-	2,3-difluorophenyl	389
	dimethylphenoxy
	4-chloro-3,5-	2,6-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-3,5-	3,4-difluorophenyl	389
	dimethylphenoxy
	4-chloro-3,5-	2,5-difluorophenyl	389
	dimethylphenoxy
	4-chloro-3,5-	4-ethoxyphenyl	397
	dimethylphenoxy
	4-chloro-3,5-	2,4,6-trichlorophenyl	456
	dimethylphenoxy
	4-chloro-3,5-	3-methylphenyl	367
	dimethylphenoxy
	4-chloro-3,5-	2-fluoro-5-	439
	dimethylphenoxy	(trifluoromethyl)phenyl
	4-chloro-3,5-	3-methoxyphenyl	383
	dimethylphenoxy
	4-chloro-3,5-	2-bromophenyl	432
	dimethylphenoxy
	4-chloro-3,5-	4-bromophenyl	432
	dimethylphenoxy
	4-chloro-3,5-	4-fluoro-3-	439
	dimethylphenoxy	(trifluoromethyl)phenyl
	4-chloro-3,5-	3-(trifluoromethoxy)phenyl	437
	dimethylphenoxy
	4-chloro-3,5-	9-fluorenon-4-yl	455
	dimethylphenoxy
	4-chloro-3,5-	isoxazol-5-yl	344
	dimethylphenoxy
	4-chloro-3,5-	benzofuroxan-5-yl	411
	dimethylphenoxy
	4-chloro-3,5-	2-chloropyrid-3-yl	388
	dimethylphenoxy
	4-chloro-3,5-	2-(4-	460
	dimethylphenoxy	methylphenoxy)pyridin-3-yl
	4-chloro-3,5-	pyridin-4-yl	354
	dimethylphenoxy
	4-chloro-3,5-	anthraquinon-2-yl	483
	dimethylphenoxy
	4-chloro-3,5-	2-iodophenyl	479
	dimethylphenoxy
	4-chloro-3,5-	4-pentylphenyl	423
	dimethylphenoxy
	4-chloro-3,5-	2-(4-chlorophenylthio)	496
	dimethylphenoxy	pyridin-3-yl
	4-chloro-3,5-	2,6-dimethylphenyl	381
	dimethylphenoxy
	4-chloro-3,5-	2,5-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-3,5-	2,5-dichloropyridin-3-yl	423
	dimethylphenoxy
	4-chloro-3,5-	2-chloro-6-methoxypyridin	418
	dimethylphenoxy	4-yl
	4-chloro-3,5-	2,3-dichloropyridin-5-yl	423
	dimethylphenoxy
	4-chloro-3,5-	1-naphthyl	417
	dimethylphenoxy
	4-chloro-3,5-	2,4-dimethoxyphenyl	413
	dimethylphenoxy
	4-chloro-3,5-	3,5-	489
	dimethylphenoxy	bis(trifluoromethyl)phenyl
	4-chloro-3,5-	2-(4-	480
	dimethylphenoxy	chlorophenoxy)pyridin-3-yl
	4-chloro-3,5-	pentafluorophenyl	443
	dimethylphenoxy
	pyrid-3-yloxy	3,4-dimethoxyphenyl	351
	pyrid-3-yloxy	2-(trifluoromethyl)phenyl	359
	pyrid-3-yloxy	2,4-difluorophenyl	327
	pyrid-3-yloxy	3-(trifluoromethyl)phenyl	359
	pyrid-3-yloxy	2-naphthyl	341
	pyrid-3-yloxy	2-methoxyphenyl	321
	pyrid-3-yloxy	3,4,5-trimethylphenyl	381
	pyrid-3-yloxy	3,4-dichlorophenyl	360
	pyrid-3-yloxy	3-bromophenyl	370
	pyrid-3-yloxy	3-pyridyl	292
	pyrid-3-yloxy	2-ethoxynaphth-1-yl	385
	pyrid-3-yloxy	2,3-dichlorophenyl	360
	pyrid-3-yloxy	6-chloropyrid-3-yl	327
	pyrid-3-yloxy	4-(trifluoromethoxy)phenyl	375
	pyrid-3-yloxy	2-fluoro-4-	377
		(trifluoromethyl)phenyl
	pyrid-3-yloxy	3-bromothienyl	376
	pyrid-3-yloxy	2-acetoxyphenyl	349
	pyrid-3-yloxy	5-methylisoxazol-3-yl	296
	pyrid-3-yloxy	2-(phenylthio)pyrid-3-yl	400
	pyrid-3-yloxy	2-(trifluoromethoxy)phenyl	375
	pyrid-3-yloxy	1-phenyl-5-propylpyrazin	399
		4-yl
	pyrid-3-yloxy	2-ethoxyphenyl	335
	pyrid-3-yloxy	3-chlorothien-2-yl	332
	pyrid-3-yloxy	1-(2-(2-methyl)propyl)-3-	351
		methylpyrazol-5-yl
	pyrid-3-yloxy	3,5-dichlorophenyl	360
	pyrid-3-yloxy	2-(propylthio)pyridin-3-yl	366
	pyrid-3-yloxy	2-(ethylthio)pyridin-3-yl	352
	pyrid-3-yloxy	3-bromopyridin-5-yl	371
	pyrid-3-yloxy	4-methyl-1,2,3-thiadiazol-	313
		5-yl
	pyrid-3-yloxy	1-methyl-3-(2-(2-	351
		methyl)propyl)pyrazol-5-yl
	pyrid-3-yloxy	3-chlorobenzo[b]thiophen-	382
		2-yl
	pyrid-3-yloxy	4-chlorophenyl	326
	pyrid-3-yloxy	4-methyl-2-phenyl-1,2,3-	372
		triazol-5-yl
	pyrid-3-yloxy	benzo[b]thiophen-2-yl	347
	pyrid-3-yloxy	3,4-dimethylphenyl	319
	pyrid-3-yloxy	2-(phenoxy)pyridin-3-yl	384
	pyrid-3-yloxy	2-(methylthio)pyridin-3-yl	338
	pyrid-3-yloxy	5-methyl-3-phenylisoxazol	372
		4-yl
	pyrid-3-yloxy	4-chloro-1,3-dimethyl	395
		pyrazolo[3,4-b]pyridin-3-
		yl
	pyrid-3-yloxy	2-chloro-6-methylpyridin	341
		4-yl
	pyrid-3-yloxy	3,5-dimethylisoxazol-4-yl	310
	pyrid-3-yloxy	1-naphthyl	341
	pyrid-3-yloxy	2-fluorophenyl	309
	pyrid-3-yloxy	4-propylphenyl	333
	pyrid-3-yloxy	3-fluorophenyl	309
	pyrid-3-yloxy	2,6-difluorophenyl	327
	pyrid-3-yloxy	2-chlorophenyl	326
	pyrid-3-yloxy	3-(chloromethyl)phenyl	340
	pyrid-3-yloxy	4-(2-(2-	347
		methyl)propyl)phenyl
	pyrid-3-yloxy	3-chlorophenyl	326
	pyrid-3-yloxy	3,5-dimethoxyphenyl	351
	pyrid-3-yloxy	2,6-dichlorophenyl	360
	pyrid-3-yloxy	2,4-dichlorophenyl	360
	pyrid-3-yloxy	4-fluorophenyl	309
	pyrid-3-yloxy	4-butylphenyl	347
	pyrid-3-yloxy	2-methylphenyl	305
	pyrid-3-yloxy	phenyl	291
	pyrid-3-yloxy	4-ethylphenyl	319
	pyrid-3-yloxy	2,3-difluorophenyl	327
	pyrid-3-yloxy	2,6-dimethoxyphenyl	351
	pyrid-3-yloxy	3,4-difluorophenyl	327
	pyrid-3-yloxy	2,5-difluorophenyl	327
	pyrid-3-yloxy	4-ethoxyphenyl	335
	pyrid-3-yloxy	2,4,6-trichlorophenyl	395
	pyrid-3-yloxy	3-methylphenyl	305
	pyrid-3-yloxy	2-fluoro-5-	377
		(trifluoromethyl)phenyl
	pyrid-3-yloxy	3-methoxyphenyl	321
	pyrid-3-yloxy	2-bromophenyl	370
	pyrid-3-yloxy	4-bromophenyl	370
	pyrid-3-yloxy	4-fluoro-3-	377
		(trifluoromethyl)phenyl
	pyrid-3-yloxy	3-(trifluoromethoxy)phenyl	375
	pyrid-3-yloxy	9-fluorenon-4-yl	393
	pyrid-3-yloxy	isoxazol-5-yl	282
	pyrid-3-yloxy	benzofuroxan-5-yl	349
	pyrid-3-yloxy	2-chloropyrid-3-yl	327
	pyrid-3-yloxy	2-(4-	398
		methylphenoxy)pyridin-3-yl
	pyrid-3-yloxy	pyridin-4-yl	292
	pyrid-3-yloxy	anthraquinon-2-yl	421
	pyrid-3-yloxy	2-iodophenyl	417
	pyrid-3-yloxy	4-pentylphenyl	361
	pyrid-3-yloxy	2-(4-chlorophenylthio)	435
		pyridin-3-yl
	pyrid-3-yloxy	2,6-dimethylphenyl	319
	pyrid-3-yloxy	2,5-dimethoxyphenyl	354
	pyrid-3-yloxy	2,5-dichloropyridin-3-yl	361
	pyrid-3-yloxy	2-chloro-6-methoxypyridin-	357
		4-yl
	pyrid-3-yloxy	2,3-dichloropyridin-5-yl	361
	pyrid-3-yloxy	1-naphthyl	355
	pyrid-3-yloxy	2,4-dimethoxyphenyl	351
	pyrid-3-yloxy	3,5-	427
		bis(trifluoromethyl)phenyl
	pyrid-3-yloxy	2-(4-	419
		chlorophenoxy)pyridin-3-yl
	pyrid-3-yloxy	pentafluorophenyl	381
	4-bromophenoxy	3,4-dimethoxyphenyl	429
	4-bromophenoxy	2-(trifluoromethyl)phenyl	437
	4-bromophenoxy	2,4-difluorophenyl	405
	4-bromophenoxy	3-(trifluoromethyl)phenyl	437
	4-bromophenoxy	2-naphthyl	419
	4-bromophenoxy	2-methoxyphenyl	399
	4-bromophenoxy	3,4,5-trimethylphenyl	459
	4-bromophenoxy	3,4-dichlorophenyl	438
	4-bromophenoxy	3-bromophenyl	448
	4-bromophenoxy	3-pyridyl	370
	4-bromophenoxy	2-ethoxynaphth-1-yl	463
	4-bromophenoxy	2,3-dichlorophenyl	438
	4-bromophenoxy	6-chloropyrid-3-yl	405
	4-bromophenoxy	4-(trifluoromethoxy)phenyl	453
	4-bromophenoxy	2-fluoro-4-	455
		(trifluoromethyl)phenyl
	4-bromophenoxy	3-bromothienyl	454
	4-bromophenoxy	2-acetoxyphenyl	427
	4-bromophenoxy	5-methylisoxazol-3-yl	374
	4-bromophenoxy	2-(phenylthio)pyrid-3-yl	478
	4-bromophenoxy	2-(trifluoromethoxy)phenyl	453
	4-bromophenoxy	1-phenyl-5-propylpyrazin	477
		4-yl
	4-bromophenoxy	2-ethoxyphenyl	413
	4-bromophenoxy	3-chlorothien-2-yl	410
	4-bromophenoxy	1-(2-(2-methyl)propyl)-3-	429
		methylpyrazol-5-yl
	4-bromophenoxy	3,5-dichlorophenyl	438
	4-bromophenoxy	2-(propylthio)pyridin-3-yl	444
	4-bromophenoxy	2-(ethylthio)pyridin-3-yl	430
	4-bromophenoxy	3-bromopyridin-5-yl	449
	4-bromophenoxy	4-methyl-1,2,3-thiadiazol-	391
		5-yl
	4-bromophenoxy	1-methyl-3-(2-(2-	429
		methyl)propyl)pyrazol-5-yl
	4-bromophenoxy	3-chlorobenzo[b]thiophen-	460
		2-yl
	4-bromophenoxy	4-chlorophenyl	404
	4-bromophenoxy	4-methyl-2-phenyl-1,2,3-	450
		triazol-5-yl
	4-bromophenoxy	benzo[b]thiophen-2-yl	425
	4-bromophenoxy	3,4-dimethylphenyl	397
	4-bromophenoxy	2-(phenoxy)pyridin-3-yl	462
	4-bromophenoxy	2-(methylthio)pyridin-3-yl	416
	4-bromophenoxy	5-methyl-3-phenylisoxazol-	450
		4-yl
	4-bromophenoxy	4-chloro-1,3-dimethyl	473
		pyrazolo[3,4-b]pyridin-3-
		yl
	4-bromophenoxy	2-chloro-6-methylpyridin-	419
		4-yl
	4-bromophenoxy	3,5-dimethylisoxazol-4-yl	388
	4-bromophenoxy	1-naphthyl	419
	4-bromophenoxy	2-fluorophenyl	387
	4-bromophenoxy	4-propylphenyl	411
	4-bromophenoxy	3-fluorophenyl	387
	4-bromophenoxy	2,6-difluorophenyl	405
	4-bromophenoxy	2-chlorophenyl	414
	4-bromophenoxy	3-(chloromethyl)phenyl	418
	4-bromophenoxy	4-(2-(2-	425
		methyl)propyl)phenyl
	4-bromophenoxy	3-chlorophenyl	404
	4-bromophenoxy	3,5-dimethoxyphenyl	429
	4-bromophenoxy	2,6-dichlorophenyl	438
	4-bromophenoxy	2,4-dichlorophenyl	438
	4-bromophenoxy	4-fluorophenyl	387
	4-bromophenoxy	4-butylphenyl	425
	4-bromophenoxy	2-methylphenyl	383
	4-bromophenoxy	phenyl	369
	4-bromophenoxy	4-ethylphenyl	397
	4-bromophenoxy	2,3-difluorophenyl	405
	4-bromophenoxy	2,6-dimethoxyphenyl	429
	4-bromophenoxy	3,4-difluorophenyl	405
	4-bromophenoxy	2,5-difluorophenyl	405
	4-bromophenoxy	4-ethoxyphenyl	413
	4-bromophenoxy	2,4,6-trichlorophenyl	473
	4-bromophenoxy	3-methylphenyl	383
	4-bromophenoxy	2-fluoro-5-	455
		(trifluoromethyl)phenyl
	4-bromophenoxy	3-methoxyphenyl	399
	4-bromophenoxy	2-bromophenyl	448
	4-bromophenoxy	4-bromophenyl	448
	4-bromophenoxy	4-fluoro-3-	455
		(trifluoromethyl)phenyl
	4-bromophenoxy	3-(trifluoromethoxy)phenyl	453
	4-bromophenoxy	9-fluorenon-4-yl	471
	4-bromophenoxy	isoxazol-5-yl	360
	4-bromophenoxy	benzofuroxan-5-yl	427
	4-bromophenoxy	2-chloropyrid-3-yl	360
	4-bromophenoxy	2-(4-	476
		methylphenoxy)pyridin-3-yl
	4-bromophenoxy	pyridin-4-yl	370
	4-bromophenoxy	anthraquinon-2-yl	499
	4-bromophenoxy	2-iodophenyl	495
	4-bromophenoxy	4-pentylphenyl	439
	4-bromophenoxy	2-(4-	513
		chlorophenylthio)pyridin-
		3-yl
	4-bromophenoxy	2,6-dimethylphenyl	397
	4-bromophenoxy	2,5-dimethoxyphenyl	429
	4-bromophenoxy	2,5-dichloropyridin-3-yl	439
	4-bromophenoxy	2-chloro-6-methoxypyridin-	435
		4-yl
	4-bromophenoxy	2,3-dichloropyridin-5-yl	439
	4-bromophenoxy	1-naphthyl	433
	4-bromophenoxy	2,4-dimethoxyphenyl	429
	4-bromophenoxy	3,5-	505
		bis(trifluoromethyl)phenyl
	4-bromophenoxy	2-(4-	497
		chlorophenoxy)pyridin-3-yl
	4-bromophenoxy	pentafluorophenyl	459
	4-chloro-2-	4-biphenyl	431
	methylphenylthio
	4-chloro-2-	3,4-dimethoxyphenyl	415
	methylphenylthio
	4-chloro-2-	2-(trifluoromethyl)phenyl	423
	methylphenylthio
	4-chloro-2-	2,4-difluorophenyl	391
	methylphenylthio
	4-chloro-2-	4-cyanophenyl	380
	methylphenylthio
	4-chloro-2-	3-(trifluoromethyl)phenyl	423
	methylphenylthio
	4-chloro-2-	3-cyanophenyl	380
	methylphenylthio
	4-chloro-2-	2-naphthyl	405
	methylphenylthio
	4-chloro-2-	2-methoxyphenyl	385
	methylphenylthio
	4-chloro-2-	3,4,5-trimethylphenyl	445
	methylphenylthio
	4-chloro-2-	4-nitrophenyl	400
	methylphenylthio
	4-chloro-2-	3,4-dichlorophenyl	424
	methylphenylthio
	4-chloro-2-	5-nitrofuran-2-yl	390
	methylphenylthio
	4-chloro-2-	3-bromophenyl	434
	methylphenylthio
	4-chloro-2-	3-pyridyl	356
	methylphenylthio
	4-chloro-2-	2-ethoxynaphth-1-yl	449
	methylphenylthio
	4-chloro-2-	2,3-dichlorophenyl	424
	methylphenylthio
	4-chloro-2-	3-nitrophenyl	400
	methylphenylthio
	4-chloro-2-	6-chloropyrid-3-yl	390
	methylphenylthio
	4-chloro-2-	4-(trifluoromethoxy)phenyl	439
	methylphenylthio
	4-chloro-2-	2-fluoro-4-	441
	methylphenylthio	(trifluoromethyl)phenyl
	4-chloro-2-	3-bromothienyl	440
	methylphenylthio
	4-chloro-2-	2-acetoxyphenyl	413
	methylphenylthio
	4-chloro-2-	5-methylisoxazol-3-yl	360
	methylphenylthio
	4-chloro-2-	2-(phenylthio)pyrid-3-yl	464
	methylphenylthio
	4-chloro-2-	2-(trifluoromethoxy)phenyl	439
	methylphenylthio
	4-chloro-2-	1-phenyl-5-propylpyrazin-	463
	methylphenylthio	4-yl
	4-chloro-2-	2-ethoxyphenyl	399
	methylphenylthio
	4-chloro-2-	3-chlorothien-2-yl	395
	methylphenylthio
	4-chloro-2-	1-(2-(2-methyl)propyl)-3-	415
	methylphenylthio	methylpyrazol-5-yl
	4-chloro-2-	3,5-dichlorophenyl	424
	methylphenylthio
	4-chloro-2-	2-(propylthio)pyridin-3-yl	430
	methylphenylthio
	4-chloro-2-	2-(ethylthio)pyridin-3-yl	416
	methylphenylthio
	4-chloro-2-	3-bromopyridin-5-yl	435
	methylphenylthio
	4-chloro-2-	4-methyl-1,2,3-thiadiazol-	377
	methylphenylthio	5-yl
	4-chloro-2-	1-methyl-3-(2-(2-	415
	methylphenylthio	methyl)propyl)pyrazol-5-yl
	4-chloro-2-	3-chlorobenzo[b]thiophen-	445
	methylphenylthio	2-yl
	4-chloro-2-	4-chlorophenyl	389
	methylphenylthio
	4-chloro-2-	4-methyl-2-phenyl-1,2,3-	436
	methylphenylthio	triazol-5-yl
	4-chloro-2-	benzo[b]thiophen-2-yl	411
	methylphenylthio
	4-chloro-2-	3,4-dimethylphenyl	383
	methylphenylthio
	4-chloro-2-	2-(phenoxy)pyridin-3-yl	448
	methylphenylthio
	4-chloro-2-	2-(methylthio)pyridin-3-yl	402
	methylphenylthio
	4-chloro-2-	5-methyl-3-phenylisoxazol-	436
	methylphenylthio	4-yl
	4-chloro-2-	4-chloro-1,3-dimethyl	458
	methylphenylthio	pyrazolo[3,4-b]pyridin-3-
		yl
	4-chloro-2-	2-chloro-6-methylpyridin-	404
	methylphenylthio	4-yl
	4-chloro-2-	3,5-dimethylisoxazol-4-yl	374
	methylphenylthio
	4-chloro-2-	1-naphthyl	405
	methylphenylthio
	4-chloro-2-	2-fluorophenyl	373
	methylphenylthio
	4-chloro-2-	4-propylphenyl	397
	methylphenylthio
	4-chloro-2-	4-(trifluoromethyl)phenyl	423
	methylphenylthio
	4-chloro-2-	3-fluorophenyl	373
	methylphenylthio
	4-chloro-2-	2,6-difluorophenyl	391
	methylphenylthio
	4-chloro-2-	2-chlorophenyl	389
	methylphenylthio
	4-chloro-2-	3-(chloromethyl)phenyl	403
	methylphenylthio
	4-chloro-2-	4-(2-(2-	411
	methylphenylthio	methyl)propyl)phenyl
	4-chloro-2-	3-chlorophenyl	389
	methylphenylthio
	4-chloro-2-	2-nitrophenyl	400
	methylphenylthio
	4-chloro-2-	3,5-dimethoxyphenyl	415
	methylphenylthio
	4-chloro-2-	2,6-dichlorophenyl	424
	methylphenylthio
	4-chloro-2-	2,4-dichlorophenyl	424
	methylphenylthio
	4-chloro-2-	4-fluorophenyl	373
	methylphenylthio
	4-chloro-2-	4-butylphenyl	411
	methylphenylthio
	4-chloro-2-	2-methylphenyl	369
	methylphenylthio
	4-chloro-2-	phenyl	355
	methylphenylthio
	4-chloro-2-	4-ethylphenyl	383
	methylphenylthio
	4-chloro-2-	2,3-difluorophenyl	391
	methylphenylthio
	4-chloro-2-	2,6-dimethoxyphenyl	415
	methylphenylthio
	4-chloro-2-	3,4-difluorophenyl	391
	methylphenylthio
	4-chloro-2-	2,5-difluorophenyl	391
	methylphenylthio
	4-chloro-2-	4-ethoxyphenyl	399
	methylphenylthio
	4-chloro-2-	2,4,6-trichlorophenyl	458
	methylphenylthio
	4-chloro-2-	3-methylphenyl	369
	methylphenylthio
	4-chloro-2-	2-fluoro-5-	441
	methylphenylthio	(trifluoromethyl)phenyl
	4-chloro-2-	3-methoxyphenyl	385
	methylphenylthio
	4-chloro-2-	thien-2-yl	361
	methylphenylthio
	4-chloro-2-	2-bromophenyl	434
	methylphenylthio
	4-chloro-2-	4-bromophenyl	434
	methylphenylthio
	4-chloro-2-	4-fluoro-3-	441
	methylphenylthio	(trifluoromethyl)phenyl
	4-chloro-2-	3-(trifluoromethoxy)phenyl	439
	methylphenylthio
	4-chloro-2-	9-fluorenon-4-yl	457
	methylphenylthio
	4-chloro-2-	isoxazol-5-yl	346
	methylphenylthio
	4-chloro-2-	benzofuroxan-5-yl	413
	methylphenylthio
	4-chloro-2-	2-chloropyrid-3-yl	390
	methylphenylthio
	4-chloro-2-	3,5-difluorophenyl	391
	methylphenylthio
	4-chloro-2-	2-(4-	462
	methylphenylthio	methylphenoxy)pyridin-3-yl
	4-chloro-2-	pyridin-4-yl	356
	methylphenylthio
	4-chloro-2-	anthraquinon-2-yl	485
	methylphenylthio
	4-chloro-2-	2-iodophenyl	481
	methylphenylthio
	4-chloro-2-	4-biphenyl	414
	methylanilino
	4-chloro-2-	3,4-dimethoxyphenyl	398
	methylanilino
	4-chloro-2-	2-(trifluoromethyl)phenyl	406
	methylanilino
	4-chloro-2-	214-difluorophenyl	374
	methylanilino
	4-chloro-2-	4-cyanophenyl	363
	methylanilino
	4-chloro-2-	3-(trifluoromethyl)phenyl	406
	methylanilino
	4-chloro-2-	3-cyanophenyl	363
	methylanilino
	4-chloro-2-	2-naphthyl	388
	methylanilino
	4-chloro-2-	2-methoxyphenyl	368
	methylanilino
	4-chloro-2-	3,4,5-trimethylphenyl	428
	methylanilino
	4-chloro-2-	4-nitrophenyl	383
	methylanilino
	4-chloro-2-	3,4-dichlorophenyl	407
	methylanilino
	4-chloro-2-	5-nitrofuran-2-yl	373
	methylanilino
	4-chloro-2-	3-bromophenyl	417
	methylanilino
	4-chloro-2-	3-pyridyl	339
	methylanilino
	4-chloro-2-	2-ethoxynaphth-1-yl	432
	methylanilino
	4-chloro-2-	2,3-dichlorophenyl	407
	methylanilino
	4-chloro-2-	3-nitrophenyl	383
	methylanilino
	4-chloro-2-	6-chloropyrid-3-yl	373
	methylanilino
	4-chloro-2-	4-(trifluoromethoxy)phenyl	422
	methylanilino
	4-chloro-2-	2-fluoro-4-	424
	methylanilino	(trifluoromethyl)phenyl
	4-chloro-2-	3-bromothienyl	423
	methylanilino
	4-chloro-2-	2-acetoxyphenyl	396
	methylanilino
	4-chloro-2-	5-methylisoxazol-3-yl	343
	methylanilino
	4-chloro-2-	2-(phenylthio)pyrid-3-yl	447
	methylanilino
	4-chloro-2-	2-(trifluoromethoxy)phenyl	422
	methylanilino
	4-chloro-2-	1-phenyl-5-propylpyrazin-	446
	methylanilino	4-yl
	4-chloro-2-	2-ethoxyphenyl	382
	methylanilino
	4-chloro-2-	3-chlorothien-2-yl	378
	methylanilino
	4-chloro-2-	1-(2-(2-methyl)propyl)-3-	398
	methylanilino	methylpyrazol-5-yl
	4-chloro-2-	3,5-dichlorophenyl	407
	methylanilino
	4-chloro-2-	2-(propylthio)pyridin-3-yl	413
	methylanilino
	4-chloro-2-	2-(ethylthio)pyridin-3-yl	399
	methylanilino
	4-chloro-2-	3-bromopyridin-5-yl	418
	methylanilino
	4-chloro-2-	4-methyl-1,2,3-thiadiazol	360
	methylanilino	5-yl
	4-chloro-2-	1-methyl-3-(2-(2-	398
	methylanilino	methyl)propyl)pyrazol-5-yl
	4-chloro-2-	3-chlorobenzo[b]thiophen-	428
	methylanilino	2-yl
	4-chloro-2-	4-chlorophenyl	372
	methylanilino
	4-chloro-2-	4-methyl-2-phenyl-1,2,3-	419
	methylanilino	triazol-5-yl
	4-chloro-2-	benzo[b]thiophen-2-yl	394
	methylanilino
	4-chloro-2-	3,4-dimethylphenyl	366
	methylanilino
	4-chloro-2-	2-(phenoxy)pyridin-3-yl	431
	methylanilino
	4-chloro-2-	2-(methylthio)pyridin-3-yl	385
	methylanilino
	4-chloro-2-	5-methyl-3-phenylisoxazol-	419
	methylanilino	4-yl
	4-chloro-2-	4-chloro-1,3-dimethyl	441
	methylanilino	pyrazolo[3,4-b]pyridin-3-
		yl
	4-chloro-2-	2-chloro-6-methylpyridin-	387
	methylanilino	4-yl
	4-chloro-2-	3,5-dimethylisoxazol-4-yl	357
	methylanilino
	4-chloro-2-	1-naphthyl	388
	methylanilino
	4-chloro-2-	2-fluorophenyl	356
	methylanilino
	4-chloro-2-	4-propylphenyl	380
	methylanilino
	4-chloro-2-	4-(trifluoromethyl)phenyl	406
	methylanilino
	4-chloro-2-	3-fluorophenyl	356
	methylanilino
	4-chloro-2-	2,6-difluorophenyl	374
	methylanilino
	4-chloro-2-	2-chlorophenyl	372
	methylanilino
	4-chloro-2-	3-(chloromethyl)phenyl	386
	methylanilino
	4-chloro-2-	4-(2-(2-	394
	methylanilino	methyl)propyl)phenyl
	4-chloro-2-	3-chlorophenyl	372
	methylanilino
	4-chloro-2-	2-nitrophenyl	383
	methylanilino
	4-chloro-2-	3,5-dimethoxyphenyl	398
	methylanilino
	4-chloro-2-	2,6-dichlorophenyl	407
	methylanilino
	4-chloro-2-	2,4-dichlorophenyl	407
	methylanilino
	4-chloro-2-	4-fluorophenyl	356
	methylanilino
	4-chloro-2-	4-butylphenyl	394
	methylanilino
	4-chloro-2-	2-methylphenyl	352
	methylanilino
	4-chloro-2-	phenyl	338
	methylanilino
	4-chloro-2-	4-ethylphenyl	366
	methylanilino
	4-chloro-2-	2,3-difluorophenyl	374
	methylanilino
	4-chloro-2-	2,6-dimethoxyphenyl	398
	methylanilino
	4-chloro-2-	3,4-difluorophenyl	374
	methylanilino
	4-chloro-2-	2,5-difluorophenyl	374
	methylanilino
	4-chloro-2-	4-ethoxyphenyl	382
	methylanilino
	4-chloro-2-	2,4,6-trichlorophenyl	441
	methylanilino
	4-chloro-2-	3-methylphenyl	352
	methylanilino
	4-chloro-2-	2-fluoro-5-	424
	methylanilino	(trifluoromethyl)phenyl
	4-chloro-2-	3-methoxyphenyl	368
	methylanilino
	4-chloro-2-	thien-2-yl	344
	methylanilino
	4-chloro-2-	2-bromophenyl	417
	methylanilino
	4-chloro-2-	4-bromophenyl	417
	methylanilino
	4-chloro-2-	4-fluoro-3-	424
	methylanilino	(trifluoromethyl)phenyl
	4-chloro-2-	3-(trifluoromethoxy)phenyl	422
	methylanilino
	4-chloro-2-	9-fluorenon-4-yl	440
	methylanilino
	4-chloro-2-	isoxazol-5-yl	329
	methylanilino
	4-chloro-2-	benzofuroxan-5-yl	396
	methylanilino
	4-chloro-2-	2-chloropyrid-3-yl	373
	methylanilino
	4-chloro-2-	3,5-difluorophenyl	374
	methylanilino
	4-chloro-2-	2-(4-	445
	methylanilino	methylphenoxy)pyridin-3-yl
	4-chloro-2-	pyridin-4-yl	339
	methylanilino
	4-chloro-2-	anthraquinon-2-yl	468
	methylanilino
	4-chloro-2-	2-iodophenyl	464
	methylanilino

The compounds listed in Table 7 can be prepared from substituted 5-aminopyridine compounds and the appropriate acid chloride according to the general procedure above.

TABLE 7
R                                                                        1                                                                    X R                                                                        3
4-chloro-2-methylphenoxy         3,4-difluorphenyl
4-chloro-2 -methylphenoxy        4-pentylphenyl
4-chloro-2-methylphenoxy         2-(4-chlorophenylthio) pyridin-3-yl
4-chloro-2-methylphenoxy         2,6-dimethylphenyl
4-chloro-2-methylphenoxy         2,5-dimethoxyphenyl
4-chloro-2-methylphenoxy         2,5-dichloropyridin-3-yl
4-chloro-2-methylphenoxy         2-chloro-6-methoxypyridin-4-yl
4-chloro-2-methylphenoxy         2,3-dichloropyridin-5-yl
4-chloro-2-methylphenoxy         i-naphthyl
4-chloro-2-methylphenoxy         2,4-dimethoxyphenyl
4-chloro-2-methylphenoxy         3,5-bis(trifluoromethyl)phenyl
4-chloro-2-methylphenoxy         2-(4-chlorophenoxy)pyridin-3-yl
4-chloro-2-methylphenoxy         pentaflourophenyl
1-naphthoxy                      4-pentylphenyl
1-naphthoxy                      2-(4-chlorophenylthio) pyridin-3-yl
1-naphthoxy                      2,6-dimethylphenyl
1-naphthoxy                      2,5-dimethoxyphenyl
1-naphthoxy                      2,5-dichloropyridin-3-yl
1-naphthoxy                      2-chloro-6-methoxypyridin-4-yl
1-naphthoxy                      2,3-dichloropyridin-5-yl
1-naphthoxy                      1-naphthyl
1-naphthoxy                      2,4-dimethoxyphenyl
1-naphthoxy                      3,5-bis(trifluoromethyl) phenyl
1-naphthoxy                      2-(4-chlorophenoxy)pyridin-3-yl
1-naphthoxy                      pentafluorophenyl
2-(2-propyl)phenoxy              4-pentylphenyl
2-(2-propyl)phenoxy              2-(4-chlorophenylthio) pyridin-3-yl
2-(2-propyl)phenoxy              2,6-dimethylphenyl
2-(2-propyl)phenoxy              2,5-dimethoxyphenyl
2-(2-propyl)phenoxy              2,5-dichloropyridin-3-yl
2-(2-propyl)phenoxy              2-chloro-6-methoxypyridin-4-yl
2-(2-propyl)phenoxy              2,3-dichloropyridin-5-yl
2-(2-propyl)phenoxy              1-naphthyl
2-(2-propyl)phenoxy              2,4-dimethoxyphenyl
2-(2-propyl)phenoxy              3,5-bis(trifluoromethyl) phenyl
2-(2-propyl)phenoxy              2-(4-chlorophenoxy)pyridin-3-yl
2-(2-propyl)phenoxy              pentafluorophenyl
3-fluoro-5-methylphenoxy         4-pentylphenyl
3-fluoro-5-methylphenoxy         2-(4-chlorophenylthio) pyridin-3-yl
3-fluoro-5-methylphenoxy         2,6-dimethylphenyl
3-fluoro-5-methylphenoxy         2,5-dimethoxyphenyl
3-fluoro-5-methylphenoxy         2,5-dichloropyridin-3-yl
3-fluoro-5-methylphenoxy         2-chloro-6-methoxypyridin-4-yl
3-fluoro-5-methylphenoxy         2,3-dichloropyridin-5-yl
3-fluoro-5-methylphenoxy         1-naphthyl
3-fluoro-5-methylphenoxy         2,4-dimethoxyphenyl
3-fluoro-5-methylphenoxy         3,5-bis(trifluoromethyl) phenyl
3-fluoro-5-methylphenoxy         2-(4-chlorophenoxy)pyridin-3-yl
3-fluoro-5-methylphenoxy         pentafluorophenyl
2-methylpyrid-3-yloxy            4-pentylphenyl
2-methylpyrid-3-yloxy            2-(4-chlorophenylthio) pyridin-3-yl
2-methylpyrid-3-yloxy            2,6-dimethylphenyl
2-methylpyrid-3-yloxy            2,5-dimethoxyphenyl
2-methylpyrid-3-yloxy            2,5-dichloropyridin-3-yl
2-methylpyrid-3-yloxy            2-chloro-6-methoxypyridin-4-yl
2-methylpyrid-3-yloxy            2,3-dichloropyridin-5-yl
2-methylpyrid-3-yloxy            1-naphthyl
2-methylpyrid-3-yloxy            2,4-dimethoxyphenyl
2-methylpyrid-3-yloxy            3,5-bis(trifluoromethyl) phenyl
2-methylpyrid-3-yloxy            2-(4-chlorophenoxy)pyridin-3-yl
2-methylpyrid-3-yloxy            pentafluorophenyl
4-methoxyphenoxy                 4-biphenyl
4-methoxyphenoxy                 4-cyanophenyl
4-methoxyphenoxy                 3-cyanophenyl
4-methoxyphenoxy                 4-nitrophenyl
4-methoxyphenoxy                 5-nitrofuran-2-yl
4-methoxyphenoxy                 3-nitrophenyl
4-methoxyphenoxy                 4-(trifluoromethyl)phenyl
4-methoxyphenoxy                 2-nitrophenyl
4-methoxyphenoxy                 thien-2-yl
2-(2-propoxy)phenoxy             4-biphenyl
2-(2-propoxy)phenoxy             4-cyanophenyl
2-(2-propoxy)phenoxy             3-cyanophenyl
2-(2-propoxy)phenoxy             4-nitrophenyl
2-(2-propoxy)phenoxy             5-nitrofuran-2-yl
2-(2-propoxy)phenoxy             3-nitrophenyl
2-(2-propoxy)phenoxy             2-nitrophenyl
2-(2-propoxy)phenoxy             thien-2-yl
2-(2-propoxy)phenoxy             3,5-difluorophenyl
4-fluorophenoxy                  4-biphenyl
4-fluorophenoxy                  4-cyanophenyl
4-fluorophenoxy                  3-cyanophenyl
4-fluorophenoxy                  4-nitrophenyl
4-fluorophenoxy                  5-nitrofuran-2-yl
4-fluorophenoxy                  3-nitrophenyl
4-fluorophenoxy                  2-nitrophenyl
4-fluorophenoxy                  4-(trifluoromethyl)phenyl
4-fluorophenoxy                  thien-2-yl
4-fluorophenoxy                  3,5-difluorophenyl
4-chlorophenoxy                  4-biphenyl
4-chlorophenoxy                  4-cyanophenyl
4-chlorophenoxy                  3-cyanophenyl
4-chlorophenoxy                  4-nitrophenyl
4-chlorophenoxy                  5-nitrofuran-2-yl
4-chlorophenoxy                  3-nitrophenyl
4-chlorophenoxy                  2-nitrophenyl
4-chlorophenoxy                  4-(trifluoromethyl)phenyl
4-chlorophenoxy                  thien-2-yl
4-chlorophenoxy                  3,5-difluorophenyl
2,4-difluorophenoxy              4-biphenyl
2,4-difluorophenoxy              4-cyanophenyl
2,4-difluorophenoxy              3-cyanophenyl
2,4-difluorophenoxy              4-nitrophenyl
2,4-difluorophenoxy              5-nitrofuran-2-yl
2,4-difluorophenoxy              3-nitrophenyl
2,4-difluorophenoxy              4-(trifluoromethyl)phenyl
2,4-difluorophenoxy              2-nitrophenyl
4-chloro-2,5-dimethylphenoxy     4-biphenyl
4-chloro-2,5-dimethylphenoxy     4-cyanophenyl
4-chloro-2,5-dimethylphenoxy     3-cyanophenyl
4-chloro-2,5-dimethylphenoxy     4-nitrophenyl
4-chloro-2,5-dimethylphenoxy     5-nitrofuran-2-yl
4-chloro-2,5-dimethylphenoxy     3-nitrophenyl
4-chloro-2,5-dimethylphenoxy     4-(trifluoromethyl)phenyl
4-chloro-2,5-dimethylphenoxy     2-nitrophenyl
4-chloro-2,5-dimethylphenoxy     thien-2-yl
4-chloro-2,5-dimethylphenoxy     3,5-difluorophenyl
4-methoxyphenoxy                 3,5-difluorophenyl
2-(2-propoxy)phenoxy             4-(trifluoromethyl)phenyl
2,4-difluorophenoxy              thien-2-yl
2,4-difluorophenoxy              3,5-difluorophenyl
4-thiomethylphenoxy              4-biphenyl
4-thiomethylphenoxy              4-cyanophenyl
4-thiomethylphenoxy              3-cyanophenyl
4-thiomethylphenoxy              4-nitrophenyl
4-thiomethylphenoxy              5-nitrofuran-2-yl
4-thiomethylphenoxy              3-nitrophenyl
4-thiomethylphenoxy              4-(trifluoromethyl)phenyl
4-thiomethylphenoxy              2-nitrophenyl
4-thiomethylphenoxy              thien-2-yl
4-thiomethylphenoxy              3,5-difluorophenyl
4-(2-(2-methyl)propyl) phenoxy   4-biphenyl
4-(2-(2-methyl)propyl) phenoxy   4-cyanophenyl
4-(2-(2-methyl)propyl) phenoxy   3-cyanophenyl
4-(2-(2-methyl)propyl) phenoxy   4-nitrophenyl
4-(2-(2-methyl)propyl) phenoxy   5-nitrofuran-2-yl
4-(2-(2-methyl)propyl) phenoxy   3-nitrophenyl
4-(2-(2-methyl)propyl) phenoxy   4-(trifluoromethyl)phenyl
4-(2-(2-methyl)propyl) phenoxy   2-nitrophenyl
4-(2-(2-methyl)propyl) phenoxy   thien-2-yl
4-(2-(2-methyl)propyl) phenoxy   3,5-difluorophenyl
2,3-dimethylphenoxy              4-biphenyl
2,3-dimethylphenoxy              4-cyanophenyl
2,3-dimethylphenoxy              3-cyanophenyl
2,3-dimethylphenoxy              4-nitrophenyl
2,3-dimethylphenoxy              5-nitrofuran-2-yl
2,3-dimethylphenoxy              3-nitrophenyl
2,3-dimethylphenoxy              4-(trifluoromethyl)phenyl
2,3-dimethylphenoxy              2-nitrophenyl
2,3-dimethylphenoxy              thien-2-yl
2,3-dimethylphenoxy              3,5-difluorophenyl
3,5-(bis-2-propyl)phenoxy        4-biphenyl
3,5-(bis-2-propyl)phenoxy        4-cyanophenyl
3,5-(bis-2-propyl)phenoxy        3-cyanophenyl
3,5-(bis-2-propyl)phenoxy        4-nitrophenyl
3,5-(bis-2-propyl)phenoxy        5-nitrofuran-2-yl
3,5-(bis-2-propyl)phenoxy        3-nitrophenyl
3,5-(bis-2-propyl)phenoxy        4-(trifluoromethyl)phenyl
3,5-(bis-2-propyl)phenoxy        2-nitrophenyl
3,5-(bis-2-propyl)phenoxy        thien-2-yl
3,5-(bis-2-propyl)phenoxy        3,5-difluorophenyl
3-trifluoromethyl phenoxy        4-biphenyl
3-trifluoromethyl phenoxy        4-cyanophenyl
3-trifluoromethyl phenoxy        3-cyanophenyl
3-trifluoromethyl phenoxy        4-nitrophenyl
3-trifluoromethyl phenoxy        5-nitrofuran-2-yl
3-trifluoromethyl phenoxy        3-nitrophenyl
3-trifluoromethyl phenoxy        4-(trifluoromethyl)phenyl
3-trifluoromethyl phenoxy        2-nitrophenyl
3-trifluoromethyl phenoxy        thien-2-yl
3-trifluoromethyl phenoxy        3,5-difluorophenyl
2,6-dichlorophenoxy              4-biphenyl
2,6-dichlorophenoxy              4-cyanophenyl
2,6-dichlorophenoxy              3-cyanophenyl
2,6-dichlorophenoxy              4-nitrophenyl
2,6-dichlorophenoxy              5-nitrofuran-2-yl
2,6-dichlorophenoxy              3-nitrophenyl
2,6-dichlorophenoxy              4-(trifluoromethyl)phenyl
2,6-dichlorophenoxy              2-nitrophenyl
2,6-dichlorophenoxy              thien-2-yl
2,6-dichlorophenoxy              3,5-difluorophenyl
2,4-dichlorophenoxy              4-biphenyl
2,4-dichlorophenoxy              4-cyanophenyl
2,4-dichlorophenoxy              3-cyanophenyl
2,4-dichlorophenoxy              4-nitrophenyl
2,4-dichlorophenoxy              5-nitrofuran-2-yl
2,4-dichlorophenoxy              3-nitrophenyl
2,4-dichlorophenoxy              4-(trifluoromethyl)phenyl
2,4-dichlorophenoxy              2-nitrophenyl
2,4-dichlorophenoxy              thien-2-yl
2,4-dichlorophenoxy              3,5-difluorophenyl
4-chloro-3-methylphenoxy         4-biphenyl
4-chloro-3-methylphenoxy         4-cyanophenyl
4-chloro-3-methylphenoxy         3-cyanophenyl
4-chloro-3-methylphenoxy         4-nitrophenyl
4-chloro-3-methylphenoxy         5-nitrofuran-2-yl
4-chloro-3-methylphenoxy         3-nitrophenyl
4-chloro-3-methylphenoxy         2-nitrophenyl
4-chloro-3-methylphenoxy         thien-2-yl
4-chloro-3-methylphenoxy         3,5-difluorophenyl
4-chloro-2-cyclohexylphenoxy     4-biphenyl
4-chloro-2-cyclohexylphenoxy     4-cyanophenyl
4-chloro-2-cyclohexylphenoxy     3-cyanophenyl
4-chloro-2-cyclohexylphenoxy     4-nitrophenyl
4-chloro-2-cyclohexylphenoxy     5-nitrofuran-2-yl
4-chloro-2-cyclohexylphenoxy     3-nitrophenyl
4-chloro-2-cyclohexylphenoxy     4-(trifluoromethyl)phenyl
4-chloro-2-cyclohexylphenoxy     2-nitrophenyl
4-chloro-2-cyclohexylphenoxy     thien-2-yl
4-chloro-2-cyclohexylphenoxy     3,5-difluorophenyl
4-chloro-3,5-dimethylphenoxy     4-biphenyl
4-chloro-3,5-dimethylphenoxy     4-cyanophenyl
4-chloro-3,5-dimethylphenoxy     3-cyanophenyl
4-chloro-3,5-dimethylphenoxy     4-nitrophenyl
4-chloro-3,5-dimethylphenoxy     5-nitrofuran-2-yl
4-chloro-3,5-dimethylphenoxy     3-nitrophenyl
4-chloro-3,5-dimethylphenoxy     4-(trifluoromethyl)phenyl
4-chloro-3,5-dimethylphenoxy     2-nitrophenyl
4-chloro-3,5-dimethylphenoxy     thien-2-yl
4-chloro-3,5-dimethylphenoxy     3,5-difluorophenyl
pyrid-3-yloxy                    4-biphenyl
pyrid-3-yloxy                    4-cyanophenyl
pyrid-3-yloxy                    3-cyanophenyl
pyrid-3-yloxy                    4-nitrophenyl
pyrid-3-yloxy                    5-nitrofuran-2-yl
pyrid-3-yloxy                    3-nitrophenyl
pyrid-3-yloxy                    4-(trifluoromethyl)phenyl
pyrid-3-yloxy                    2-nitrophenyl
pyrid-3-yloxy                    thien-2-yl
pyrid-3-yloxy                    3,5-difluorophenyl
4-bromophenoxy                   4-biphenyl
4-bromophenoxy                   4-cyanophenyl
4-bromophenoxy                   3-cyanophenyl
4-bromophenoxy                   4-nitrophenyl
4-bromophenoxy                   5-nitrofuran-2-yl
4-bromophenoxy                   3-nitrophenyl
4-bromophenoxy                   4-(trifluoromethyl)phenyl
4-bromophenoxy                   2-nitrophenyl
4-bromophenoxy                   thien-2-yl
4-bromophenoxy                   3,5-difluorophenyl
4-chloro-2-methylphenylthio      4-pentylphenyl
4-chloro-2-methylphenylthio      2-(4-chlorophenylthio) pyridin-3-yl
4-chloro-2-methylphenylthio      2,6-dimethylphenyl
4-chloro-2-methylphenylthio      2,5-dimethoxyphenyl
4-chloro-2-methylphenylthio      2,5-dichloropyridin-3-yl
4-chloro-2-methylphenylthio      2-chloro-6-methoxypyridin-4-yl
4-chloro-2-methylphenylthio      2,3-dichloropyridin-5-yl
4-chloro-2-methylphenylthio      1-naphthyl
4-chloro-2-methylphenylthio      2,4-dimethoxyphenyl
4-chloro-2-methylphenylthio      3,5-bis(trifluoromethyl) phenyl
4-chloro-2-methylphenylthio      2-(4-chlorophenoxy)pyridin-3-yl
4-chloro-2-methylphenylthio      pentafluorophenyl
4-chloro-2-methylanilino         4-pentylphenyl
4-chloro-2-methylanilino         2-(4-chlorophenylthio) pyridin-3-yl
4-chloro-2-methylanilino         2,6-dimethylphenyl
4-chloro-2-methylanilino         2,5-dimethoxyphenyl
4-chloro-2-methylanilino         2,5-dichloropyridin-3-yl
4-chloro-2-methylanilino         2-chloro-6-methoxypyridin-4-yl
4-chloro-2-methylanilino         2,3-dichloropyridin-5-yl
4-chloro-2-methylanilino         1-naphthyl
4-chloro-2-methylanilino         2,4-dimethoxyphenyl
4-chloro-2-methylanilino         3,5-bis(trifluoromethyl)phenyl
4-chloro-2-methylanilino         2-(4-chlorophenoxy)pyridin-3-yl
4-chloro-2-methylanilino         pentafluorophenyl

EXAMPLE 19

General Procedure for the Synthesis of 6(substituted-amino)-N-substituted nocotinamides

Step A. General Procedure for the Preparation of 6-chloro-N-substituted Nicotinamide:

To a suspension of 6-chloronicotinoyl chloride (1.76 g, 10.0 mmol) in dry-dichloromethane (10 mL) was added the amine (R 3 R 4 NH) (10.0 mmol) followed by the dropwise addition of triethylamine (1.7 mL, 12.2 mmol), After stirring for 40 min. at room temperature, the mixture was diluted with dichloromethane, washed with aqueous 1 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate and water, dried over sodium sulfate and concentrated to dryness under reduce pressure to afford the desired nicotinamide.

The following compounds were prepared according to this procedure using the appropriate substituted amine:

6-Chloro-N-o-tolylnicotinamide: MS (m/z): 247/249 (M+H) + ; C 13 H 11 Cl 1 N 2 O 1 , requires 246.5.

6-Chloro-N-(2-fluorophenyl)nicotinamide: MS (m/z): 251/253 (M+H) + ; C 12 H 8 Cl 1 F 1 N 2 O 1 requires 250.7.

6-Chloro-N-(2,6-dimethylphenyl)nicotinamide: MS (m/z): 261/263 (M+H) + ; C 14 H 13 Cl 1 N 2 O 1 requires 260.7.

6-Chloro-N-(2-phenoxyphenyl)nicotinamide: MS (m/z): 325/327 (M+H) + ; C 18 H 13 Cl 1 N 2 O 1 requires 324.8.

6-Chloro-N-phenylnicotinamide: MS (m/z): 233/235 (M+H) + ; C 12 H 8 Cl 1 N 2 O 1 requires 232.7.

6-Chloro-N-(2,4-difluorophenyl)nicotinamide: MS (m/z): 269/271 (M+H) + ; C 12 H 7 Cl 1 F 2 N 2 O 1 requires 268.6.

6-Chloro-N-(2,6-diisopropylphenyl)nicotinamide: MS (m/z): 317/319 (M+H) + ; C 18 H 21 Cl 1 N 2 Orequires 316.8.

6-Chloro-N-(4-chlorophenyl)-N-methylnicotinamide: MS (m/z): 281/283 (M+H) + ; C 13 H 10 Cl 2 O 1 requires 281.1.

6-Chloro-N-(2,4-dimethoxyphenyl)nicotinamide: MS (m/z): 293/295 (M+H) + ; C 14 H 13 Cl 1 N 2 O 3 requires 292.7.

6-Chloro-N-(3-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H) + ; C 13 H 11 Cl 1 N 2 O 2 requires 262.7.

6-Chloro-N-(4-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H) + ; C 13 H 11 Cl 1 N 2 O 2 requires 262.7.

6-Chloro-N-(2-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H) + ; C 13 H 11 Cl 1 N 2 O 2 requires 262.7.

6-Chloro-N-methyl-N-phenylnicotinamide: MS (m/z): 247/249 (M+H) + ; C 13 H 11 Cl 1 N 2 O 1 requires 246.7.

N-Benzyl-6-chloronicotinamide: MS (m/z): 247/249 (M+H) + ; C 13 H 11 Cl 1 N 2 O 1 requires 246.7.

Step B. General Procedure for the Preparation of 6-(substituted-amino)-N-substituted Nicotinamides

A mixture of the 6-chloro-N-substituted nicotinamide (12.5 mmol) and amine (R 1 NH 2 or R 1 NHCH 3 ) (20 mmol) in ethylene glycol (50 mL) or pyridine (alkylamines) (50 mL) was heated to 140° for 20 hours. After cooling to room temperature, the mixture was diluted with dichloromethane/methanol (9:1, 250 mL) and filtered through a plug of silica gel, washing with additional dichloromethane/methanol (9:1, 250 mL). Concentration under reduced pressure afforded the desired 6-(substituted-amino)-N-substituted nicotinamide.

The compounds listed in Tables 8-11 were prepared from 6-chloro-N-substituted nicotinamides compounds and the appropriate amine according to the general procedure above.

TABLE 8
	R 3	R 1	MS (m/z)
	o-tolyl	phenyl	303
	o-tolyl	o-tolyl	317
	o-tolyl	4-chloro-2-methylphenyl	352
	o-tolyl	2-fluorophenyl	321
	o-tolyl	3-fluorophenyl	321
	o-tolyl	4-fluorophenyl	321
	o-tolyl	2,4-difluorophenyl	339
	o-tolyl	2-methoxyphenyl	333
	o-tolyl	3-methoxyphenyl	333
	o-tolyl	4-methoxyphenyl	333
	o-tolyl	2,4-dimethoxyphenyl	363
	o-tolyl	2-phenoxyphenyl	395
	o-tolyl	3-phenoxyphenyl	395
	o-tolyl	4-phenoxyphenyl	395
	o-tolyl	4-biphenyl	379
	o-tolyl	4-benzylphenyl	393
	o-tolyl	4-(trifluoromethoxy)phenyl	387
	o-tolyl	cyclohexyl	309
	o-tolyl	2-methylcyclohexyl	323
	o-tolyl	cycloheptyl	323
	o-tolyl	indan-1-yl	343
	o-tolyl	2-dicyclohexyl	492
	2-fluorophenyl	phenyl	307
	2-fluorophenyl	o-tolyl	321
	2-fluorophenyl	4-chloro-2-methylphenyl	356
	2-fluorophenyl	2-fluorophenyl	325
	2-fluorophenyl	3-fluorophenyl	325
	2-fluorophenyl	4-fluorophenyl	325
	2-fluorophenyl	2,4-difluorophenyl	343
	2-fluorophenyl	2-methoxyphenyl	337
	2-fluorophenyl	3-methoxyphenyl	337
	2-fluorophenyl	4-methoxyphenyl	337
	2-fluorophenyl	2,4-dimethoxyphenyl	367
	2-fluorophenyl	2-phenoxyphenyl	399
	2-fluorophenyl	3-phenoxyphenyl	399
	2-fluorophenyl	4-phenoxyphenyl	399
	2-fluorophenyl	4-biphenyl	383
	2-fluorophenyl	4-benzylphenyl	397
	2-fluorophenyl	4-(trjfluoromethoxy)phenyl	391
	2-fluorophenyl	cyclohexyl	313
	2-fluorophenyl	2-methylcyclohexyl	327
	2-fluorophenyl	cycloheptyl	327
	2-fluorophenyl	indan-1-yl	347
	2-fluorophenyl	2-dicyclohexyl	395
	2,6-dimethylphenyl	phenyl	317
	2,6-dimethylphenyl	o-tolyl	331
	2,6-dimethylphenyl	4-chloro-2-methylphenyl	366
	2,6-dimethylphenyl	2-fluorophenyl	335
	2,6-dimethylphenyl	3-fluorophenyl	335
	2,6-dimethylphenyl	4-fluorophenyl	335
	2,6-dimethylphenyl	2,4-difluorophenyl	353
	2,6-dimethylphenyl	2-methoxyphenyl	347
	2,6-dimethylphenyl	3-methoxyphenyl	347
	2,6-dimethylphenyl	4-methoxyphenyl	347
	2,6-dimethylphenyl	2,4-dimethoxyphenyl	377
	2,6-dimethylphenyl	2-phenoxyphenyl	409
	2,6-dimethylphenyl	3-phenoxyphenyl	409
	2,6-dimethylphenyl	4-phenoxyphenyl	409
	2,6-dimethylphenyl	4-biphenyl	393
	2,6-dimethylphenyl	4-benzylphenyl	407
	2,6-dimethylphenyl	4-(trifluoromethoxy)phenyl	401
	2,6-dimethylphenyl	cyclohexyl	323
	2,6-dimethylphenyl	2-methylcyclohexyl	337
	2,6-dimethylphenyl	cycloheptyl	667
	2,6-dimethylphenyl	indan-1-yl	357
	2,6-dimethylphenyl	2-dicyclohexyl	406
	2-phenoxyphenyl	phenyl	381
	2-phenoxyphenyl	o-tolyl	395
	2-phenoxyphenyl	4-chloro-2-methylphenyl	430
	2-phenoxyphenyl	2-fluorophenyl	399
	2-phenoxyphenyl	3-fluorophenyl	399
	2-phenoxyphenyl	4-fluorophenyl	399
	2-phenoxyphenyl	2,4-difluorophenyl	417
	2-phenoxyphenyl	2-methoxyphenyl	411
	2-phenoxyphenyl	3-methoxyphenyl	411
	2-phenoxyphenyl	4-methoxyphenyl	411
	2-phenoxyphenyl	2,4-dimethoxyphenyl	441
	2-phenoxyphenyl	2-phenoxyphenyl	473
	2-phenoxyphenyl	3-phenoxyphenyl	473
	2-phenoxyphenyl	4-phenoxyphenyl	473
	2-phenoxyphenyl	4-biphenyl	457
	2-phenoxyphenyl	4-benzylphenyl	472
	2-phenoxyphenyl	4-(trifluoromethoxy)phenyl	465
	2-phenoxyphenyl	cyclohexyl	387
	2-phenoxyphenyl	2 methylcyclohexyl	401
	2-phenoxyphenyl	cycloheptyl	401
	2-phenoxyphenyl	indan-1-yl	421
	2-phenoxyphenyl	2-dicyclohexyl	470
	phenyl	phenyl	289
	phenyl	o-tolyl	303
	phenyl	4-chloro-2-methylphenyl	338
	phenyl	2-fluorophenyl	307
	phenyl	3-fluorophenyl	307
	phenyl	4-fluorophenyl	307
	phenyl	2,4-difluorophenyl	325
	phenyl	2-methoxyphenyl	319
	phenyl	3-methoxyphenyl	319
	phenyl	4-methoxyphenyl	319
	phenyl	2,4-dimethoxyphenyl	349
	phenyl	2-phenoxyphenyl	381
	phenyl	3-phenoxyphenyl	381
	phenyl	4-phenoxyphenyl	381
	phenyl	4-biphenyl	365
	phenyl	4-benzylphenyl	379
	phenyl	4-(trifluoromethoxy)phenyl	373
	phenyl	cyclohexyl	295
	phenyl	2-methylcyclohexyl	309
	phenyl	cycloheptyl	309
	phenyl	indan-1-yl	329
	phenyl	2-dicyclohexyl	377
	2,4-difluorophenyl	phenyl	325
	2,4-difluorophenyl	o-tolyl	339
	2,4-difluorophenyl	4-chloro-2-methylphenyl	374
	2,4-difluorophenyl	2-fluorophenyl	343
	2,4-difluorophenyl	3-fluorophenyl	343
	2,4-difluorophenyl	4-fluorophenyl	343
	2,4-difluorophenyl	2,4-difluorophenyl	361
	2,4-difluorophenyl	2-methoxyphenyl	355
	2,4-difluorophenyl	3-methoxyphenyl	355
	2,4-difluorophenyl	4-methoxyphenyl	355
	2,4-difluorophenyl	2,4-dimethoxyphenyl	385
	2,4-difluorophenyl	2-phenoxyphenyl	417
	2,4-difluorophenyl	3-phenoxyphenyl	417
	2,4-difluorophenyl	4-phenoxyphenyl	417
	2,4-difluorophenyl	4-biphenyl	401
	2,4-difluorophenyl	4-benzylphenyl	415
	2,4-difluorophenyl	4-(trifluoromethoxy)phenyl	409
	2,4-difluorophenyl	cyclohexyl	331
	2,4-difluorophenyl	2-methylcyclohexyl	345
	2,4-difluorophenyl	cycloheptyl	345
	2,4-difluorophenyl	indan-1-yl	365
	2,4-difluorophenyl	2-dicyclohexyl	413
	2,6-diisopropylphenyl	phenyl	373
	2,6-diisopropylphenyl	o-tolyl	387
	2,6-diisopropylphenyl	4-chloro-2-methylphenyl	422
	2,6-diisopropylphenyl	2-fluorophenyl	391
	2,6-diisopropylphenyl	3-fluorophenyl	391
	2,6-diisopropylphenyl	4-fluorophenyl	391
	2,6-diisopropylphenyl	2,4-difluorophenyl	409
	2,6-diisopropylphenyl	2-methoxyphenyl	403
	2,6-diisopropylphenyl	3-methoxyphenyl	403
	2,6-diisopropylphenyl	4-methoxyphenyl	403
	2,6-diisopropylphenyl	2,4-dimethoxyphenyl	434
	2,6 diisopropylphenyl	2-phenoxyphenyl	466
	2,6-diisopropylphenyl	3-phenoxyphenyl	466
	2,6-diisopropylphenyl	4-phenoxyphenyl	466
	2,6-diisopropylphenyl	4-biphenyl	450
	2,6-diisopropylphenyl	4-benzylphenyl	464
	2,6-diisopropylphenyl	4-(trifluoromethoxy)phenyl	457
	2,6-diisopropylphenyl	cyclohexyl	380
	2,6-diisopropylphenyl	2-methylcyclohexyl	394
	2,6-diisopropylphenyl	cycloheptyl	394
	2,6-diisopropylphenyl	indan-1-yl	414
	2,6-diisopropylphenyl	2-dicyclohexyl	462
	2,4-dimethoxyphenyl	phenyl	349
	2,4-dimethoxyphenyl	o-tolyl	363
	2,4-dimethoxyphenyl	4-chloro-2-methylphenyl	398
	2,4-dimethoxyphenyl	2-fluorophenyl	367
	2,4-dimethoxyphenyl	3-fluorophenyl	367
	2,4-dimethoxyphenyl	4-fluorophenyl	367
	2,4-dimethoxyphenyl	2,4-difluorophenyl	385
	2,4-dimethoxyphenyl	2-methoxyphenyl	379
	2,4-dimethoxyphenyl	3-methoxyphenyl	379
	2,4-dimethoxyphenyl	4-methoxyphenyl	379
	2,4-dimethoxyphenyl	2,4-dimethoxyphenyl	409
	2,4-dimethoxyphenyl	2-phenoxyphenyl	441
	2,4-dimethoxyphenyl	3-phenoxyphenyl	441
	2,4-dimethoxyphenyl	4-phenoxyphenyl	441
	2,4-dimethoxyphenyl	4-biphenyl	425
	2,4-dimethoxyphenyl	4-benzylphenyl	439
	2,4-dimethoxyphenyl	4-(trifluoromethoxy)phenyl	433
	2,4-dimethoxyphenyl	3-trifluoromethylphenyl	417
	2,4-dimethoxyphenyl	cyclohexyl	355
	2,4-dimethoxyphenyl	2-methylcyclohexyl	369
	3-methoxyphenyl	phenyl	319
	3-methoxyphenyl	o-tolyl	333
	3-methoxyphenyl	4-chloro-2-methylphenyl	368
	3-methoxyphenyl	2-fluorophenyl	337
	3-methoxyphenyl	3-fluorophenyl	337
	3-methoxyphenyl	4-fluorophenyl	337
	3-methoxyphenyl	2,4-difluorophenyl	355
	3-methoxyphenyl	2-methoxyphenyl	349
	3-methoxyphenyl	3-methoxyphenyl	349
	3-methoxyphenyl	4-methoxyphenyl	349
	3-methoxyphenyl	2,4-dimethoxyphenyl	379
	3-methoxyphenyl	2-phenoxyphenyl	411
	3-methoxyphenyl	3-phenoxyphenyl	411
	3-methoxyphenyl	4-phenoxyphenyl	411
	3-methoxyphenyl	4-biphenyl	395
	3-methoxyphenyl	4-benzylphenyl	409
	3-methoxyphenyl	4-(trifluoromethoxy)phenyl	403
	3-methoxyphenyl	3-trifluoromethylphenyl	387
	3-methoxyphenyl	cyclohexyl	625
	3-methoxyphenyl	2-methylcyclohexyl	339
	4-methoxyphenyl	phenyl	319
	4-methoxyphenyl	o-tolyl	333
	4-methoxyphenyl	4-chloro-2-methylphenyl	368
	4-methoxyphenyl	2-fluorophenyl	337
	4-methoxyphenyl	3-fluorophenyl	337
	4-methoxyphenyl	4-fluorophenyl	337
	2,4-dimethoxyphenyl	cyclohexyl	355
	2,4-dimethoxyphenyl	2-methylcyclohexyl	369
	3-methoxyphenyl	phenyl	319
	3-methoxyphenyl	o-tolyl	333
	3-methoxyphenyl	4-chloro-2-methylphenyl	368
	3-methoxyphenyl	2-fluorophenyl	337
	3-methoxyphenyl	3-fluorophenyl	337
	3-methoxyphenyl	4-fluorophenyl	337
	3-methoxyphenyl	2,4-difluorophenyl	355
	3-methoxyphenyl	2-methoxyphenyl	349
	3-methoxyphenyl	3-methoxyphenyl	349
	3-methoxyphenyl	4-methoxyphenyl	349
	3-methoxyphenyl	2,4-dimethoxyphenyl	379
	3-methoxyphenyl	2-phenoxyphenyl	411
	3-methoxyphenyl	3-phenoxyphenyl	411
	3-methoxyphenyl	4-phenoxyphenyl	411
	3-methoxyphenyl	4-biphenyl	395
	3-methoxyphenyl	4-benzylphenyl	409
	3-methoxyphenyl	4-(trifluoromethoxy)phenyl	403
	3-methoxyphenyl	3-trifluoromethylphenyl	387
	3-methoxyphenyl	cyclohexyl	625
	3-methoxyphenyl	2-methylcyclohexyl	339
	4-methoxyphenyl	phenyl	319
	4-methoxyphenyl	o-tolyl	333
	4-methoxyphenyl	4-chloro-2-methylphenyl	368
	4-methoxyphenyl	2-fluorophenyl	337
	4-methoxyphenyl	3-fluorophenyl	337
	4-methoxyphenyl	4-fluorophenyl	337
	4-methoxyphenyl	2,4-difluorophenyl	355
	4-methoxyphenyl	2-methoxyphenyl	349
	4-methoxyphenyl	3-methoxyphenyl	349
	4-methoxyphenyl	4-methoxyphenyl	349
	4-methoxyphenyl	2,4-dimethoxyphenyl	379
	4-methoxyphenyl	2-phenoxyphenyl	411
	4-methoxyphenyl	3-phenoxyphenyl	411
	4-methoxyphenyl	4-phenoxyphenyl	411
	4-methoxyphenyl	4-biphenyl	395
	4-methoxyphenyl	4-benzylphenyl	409
	4-methoxyphenyl	4-(trifluoromethoxy)phenyl	403
	4-methoxyphenyl	3-trifluoromethylphenyl	387
	4-methoxyphenyl	cyclohexyl	625
	4-methoxyphenyl	2-methylcyclohexyl	339
	2-methoxyphenyl	phenyl	319
	2-methoxyphenyl	o-tolyl	333
	2-methoxyphenyl	4-chloro-2-methylphenyl	368
	2-methoxyphenyl	2-fluorophenyl	337
	2-methoxyphenyl	3-fluorophenyl	337
	2-methoxyphenyl	4-fluorophenyl	337
	2-methoxyphenyl	2,4-difluorophenyl	355
	2-methoxyphenyl	2-methoxyphenyl	349
	2-methoxyphenyl	3-methoxyphenyl	349
	2-methoxyphenyl	4-methoxyphenyl	349
	2-methoxyphenyl	2,4-dimethoxyphenyl	379
	2-methoxyphenyl	2-phenoxyphenyl	411
	2-methoxyphenyl	3-phenoxyphenyl	411
	2-methoxyphenyl	4-phenoxyphenyl	411
	2-methoxyphenyl	4-biphenyl	395
	2-methoxyphenyl	4-benzylphenyl	409
	2-methoxyphenyl	4-(trifluoromethoxy)phenyl	403
	2-methoxyphenyl	3-trifluoromethylphenyl	387
	2-methoxyphenyl	cyclohexyl	625
	2-methoxyphenyl	2-methylcyclohexyl	339

TABLE 9
	R 3	R 1	MS (m/z)
	4-chlorophenyl	phenyl	338
	4-chlorophenyl	o-tolyl	352
	4-chlorophenyl	4-chloro-2-methylphenyl	386
	4-chlorophenyl	2-fluorophenyl	356
	4-chlorophenyl	3-fluorophenyl	356
	4-chlorophenyl	4-fluorophenyl	356
	4-chlorophenyl	2,4-difluorophenyl	374
	4-chlorophenyl	2-methoxyphenyl	368
	4-chlorophenyl	3-methoxyphenyl	368
	4-chlorophenyl	4-methoxyphenyl	368
	4-chlorophenyl	2,4-dimethoxyphenyl	398
	4-chlorophenyl	2-phenoxyphenyl	430
	4-chlorophenyl	3-phenoxyphenyl	430
	4-chlorophenyl	4-phenoxyphenyl	430
	4-chlorophenyl	4-biphenyl	414
	4-chlorophenyl	4-benzylphenyl	428
	4-chlorophenyl	4-(trifluoromethoxy)phenyl	422
	4-chlorophenyl	cyclohexyl	344
	4-chlorophenyl	2-methylcyclohexyl	358
	phenyl	phenyl	303
	phenyl	o-tolyl	317
	phenyl	4-chloro-2-methylphenyl	352
	phenyl	2-fluorophenyl	321
	phenyl	3-fluorophenyl	321
	phenyl	4-fluorophenyl	321
	phenyl	2,4-difluorophenyl	339
	phenyl	2-methoxyphenyl	333
	phenyl	3-methoxyphenyl	333
	phenyl	4-methoxyphenyl	333
	phenyl	2,4-dimethoxyphenyl	363
	phenyl	2-phenoxyphenyl	395
	phenyl	3-phenoxyphenyl	395
	phenyl	4-phenoxyphenyl	395
	phenyl	4-biphenyl	379
	phenyl	4-benzylphenyl	393
	phenyl	4-(trifluoromethoxy)phenyl	387
	phenyl	3-trifluoromethylphenyl	371
	phenyl	cyclohexyl	309
	phenyl	2-methylcyclohexyl	323

TABLE 10
			MS
	R 3	R 1	(m/z)
	o-tolyl	N-methylphenyl	317
	o-tolyl	4-chloro-N-methylphenyl	352
	o-tolyl	N-methylcyclohexyl	323
	2-fluorophenyl	N-methylphenyl	321
	2-fluorophenyl	4-chloro-N-methylphenyl	356
	2-fluorophenyl	N-methylcyclohexyl	327
	2,6-dimethylphenyl	N-methylphenyl	331
	2,6-dimethylphenyl	4-chloro-N-methylphenyl	366
	2,6-dimethylphenyl	N-methylcyclohexyl	337
	2-phenoxyphenyl	N-methylphenyl	395
	2-phenoxyphenyl	4-chloro-N-methylphenyl	430
	2-phenoxyphenyl	N-methylcyclohexyl	401
	phenyl	N-methylphenyl	303
	phenyl	4-chloro-N-methylphenyl	338
	phenyl	N-methylcyclohexyl	309
	2,4-difluorophenyl	N-methylphenyl	339
	2,4-difluorophenyl	4-chloro-N-methylphenyl	374
	2,4-difluorophenyl	N-methylcyclohexyl	345
	2,6-diisopropylphenyl	N-methylphenyl	387
	2,6-diisopropylphenyl	4-chloro-N-methylphenyl	422
	2,6-diisopropylphenyl	N-methylcyclohexyl	394
	2,4-dimethyloxyphenyl	N-methylphenyl	363
	2,4-dimethyloxyphenyl	4-chloro-N-methylphenyl	398
	2,4-dimethyloxyphenyl	N-methylcyclohexyl	369
	3-methoxyphenyl	N-methylphenyl	333
	3-methoxyphenyl	4-chloro-N-methylphenyl	368
	3-methoxyphenyl	N-methylcyclohexyl	339
	4-methoxyphenyl	N-methylphenyl	333
	4-methoxyphenyl	4-chloro-N-methylphenyl	368
	4-methoxyphenyl	N-methylcyclohexyl	339
	2-methoxyphenyl	N-methylphenyl	333
	2-methoxyphenyl	4-chloro-N-methylphenyl	368
	2-methoxyphenyl	N-methylcyclohexyl	339

TABLE 11
			MS
	R 3	R 1	(m/z)
	4-chlorophenyl	phenyl	352
	4-chlorophenyl	4-chlorophenyl	386
	4-chlorophenyl	cyclohexyl	358
	phenyl	phenyl	317
	phenyl	4-chlorophenyl	352
	phenyl	cyclohexyl	323

The compounds listed in Tables 12-13 can be prepared from 6-chloro-N-substituted nicotinamides compounds and the appropriate amine according to the general procedure above.

TABLE 12
R                                                                        1                                                                    X R                                                                        3
o-tolyl                          3-trifluoromethylphenyl
2-fluorophenyl                   3-trifluoromethylphenyl
2,6-dimethylphenyl               3-trifluoromethylphenyl
2-phenoxyphenyl                  3-trifluoromethylphenyl
phenyl                           3-trifluoromethylphenyl
2,4-difluorophenyl               3-trifluoromethylphenyl
2,6-diisopropylphenyl            3-trifluoromethylphenyl
2,4-dimethoxyphenyl              cycloheptyl
2,4-dimethoxyphenyl              indan-1-yl
2,4-dimethoxyphenyl              2-dicyclohexyl
3-methoxyphenyl                  cycloheptyl
3-methoxyphenyl                  indan-1-yl
3-methoxyphenyl                  2-dicyclohexyl
4-methoxyphenyl                  cycloheptyl
4-methoxyphenyl                  indan-1-yl
4-methoxyphenyl                  2-dicyclohexyl
2-methoxyphenyl                  cycloheptyl
2-methoxyphenyl                  indan-1-yl
2-methoxyphenyl                  2-dicyclohexyl

TABLE 13
R                                                                        1                                                                    X R                                                                        3
4-chlorophenyl                   3-trifluoromethylphenyl
4-chlorophenyl                   cycloheptyl
4-chlorophenyl                   indan-1-yl
4-chlorophenyl                   2-dicyclohexyl
phenyl                           cycloheptyl
phenyl                           indan-1-yl
phenyl                           2-dicyclohexyl

EXAMPLE 20

The following assays were used to characterize the ability of compounds of the invention to inhibit the production of TNF-α and IL-1-β. The second assay measured the inhibition of TNT-α and/or IL-1-β in mice after oral administration of the test compounds. The third assay, a glucagon binding inhibition in vitro assay, can be used to characterize the ability of compounds of the invention to inhibit glucagon binding. The fourth assay, a Cyclooxygenase enzyme (COX-1 and COX-2) inhibition activity in vitro assay, can be used to characterize the ability of compounds of the invention to inhibit COX-1 and/or COX-2. The fifth assay, a Raf-kinase inhibition assay, can be used to characterize the compounds of the invention to inhibit phosphorylation of MEK by activated Raf-kinase.

Lipopolysaccharido-activated Monocyte TNF Production Assay

Isolation of monocytes

Test compounds were evaluated in vitro for the ability to inhibit the production of tumor necrosis factor (TNF) by monocytes activated with bacterial lipopolysaccharide (LPS). Fresh residual source leukocytes (a byproduct of plateletpheresis) were obtained from a local blood bank, and peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation on Ficol-Paque Plus (Pharmacia). PBMCs were suspended at 2×10 6 /ml in DMEM supplemented to contain 2% FCS, 10 mM, 0.3 mg/ml glutamate, 100 U/ml penicillin G and 100 mg/ml streptomycin sulfate (complete media). Cells were plated into Falcon flat bottom, 96 well culture plates (200 μl/well and cultured overnight at 37° C. and 6% CO 2 . Non-adherent cells were removed by washing with 200 μl/well of fresh medium. Wells containing adherent cells (˜70% monocytes) were replenished with 100 μl of fresh medium.

Preparation of test compound stock solutions

Test compounds were dissolved in DMSO. Compound stock solutions were prepared to an initial concentration of 10-50 μM. Stocks were diluted initially to 20-200 μM in complete media. Nine two-fold serial dilutions of each compound were then prepared in complete medium.

Treatment of cells with test compounds and activation of TNF production with lipopolysaccharide

One hundred microliters of each test compound dilution were added to microtiter wells containing adherent monocytes and 100 μl complete medium. Monocytes were cultured with test compounds for 60 min at which time 25 μl of complete medium containing 30 ng/ml lipopolysaccharide from E. Coli K532 were added to each well. Cells were cultured an additional 4 hrs. Culture supernatants were then removed and TNF presence in the supernatants was quantified using an ELISA.

TNF ELISA

Flat bottom, 96 well Corning High Binding ELISA plates were coated overnight (4° C.) with 150 μL/well of 3 μg/ml murine anti-human TNF-α MAb (R&D Systems #MAB210 ). Wells were then blocked for 1 hr at room temperature with 200 μL/well of CaCl 2 -free ELISA buffer supplemented to contain 20 mg/ml BSA (standard ELISA buffer: 20 mM, 150 mM NaCl, 2 mM CaCl 2 , 0.15 mM thimerosal, pH 7.4). Plates were washed and replenished with 100 μl of test supernatants (diluted 1:3) or standards. Standards consisted of eleven 1.5-fold serial dilutions from a stock of 1 ng/ml recombinant human TNF (R&D Systems). Plates were incubated at room temperature for 1 hr on orbital shaker (300 rpm), washed and replenished with 100 μl/well of 0.5 μg/ml goat anti-human TNF-α (R&D systems #AB-210-NA) biotinylated at a 4:1 ratio. Plates were incubated for 40 min, washed and replenished with 100 μg/well of alkaline phosphatase-conjugated streptavidin (Jackson ImmunoResearch #016-050-084) at 0.02 μg/ml Plates were incubated 30 min, washed and replenished with 200 μl/well of 1 mg/ml of p-nitrophenyl phosphate. After 30 min, plates were read at 405 nm on a V max plate reader.

Data analysis

Standard curve data were fit to a second order polynomial and unknown TNF-α concentrations determined from their OD by-solving this equation for concentration. TNF concentrations were then plotted vs. test compound concentration using a second order polynomial. This equation was then used to calculate the concentration of test compounds causing a 50% reduction in TNF production.

The following compounds had an IC 50 of less than 15 μM:

2-cyclohexyloxy-5-(2-chlorophenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2-methylphenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2,6-dichlorophenylcarbonylamino)pyridine;

2-cyclohexyloxy-5-(2,6-dimethylphenylcarbonylamino)pyridine;

2-(2,4-dimethylphenoxy)-5-(2-methylphenylcarbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2-chlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(4-chlorophenoxy)-5-(2,6-dimethylphenylcarbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine;

2-(2-methyl-4-fluorophenoxy)-5-(2-fluorophenylcarbonyl amino)pyridine;

2-(2,4-dimethylphenoxy)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(1-naphthyloxy)-5-(2-methylphenylcarbonylamino)pyridine;

2-(1-naphthyloxy)-5-(2,6-dichlorophenylcarbonylamino)pyridine;

2-(2-methyl-3-pyridyloxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenoxy)-5-((3,5-dimethyl-4-isoxazolyl)carbonylamino)pyridine;

2-cyclohexylamino-5-(2,6-dichlorophenylcarbonylamino)pyridine;

2-cyclohexylamino-5-(2,6-dimethylphenylcarbonylamino)pyridine;

2-(2-methylcyclohexylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine;

2-(2-methylcyclohexylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine;

2-(2-methylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine;

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl carbonylamino)pyridine; and

2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl aminocarbonyl)pyridine.

Compounds of the invention can also be shown to inhibit LPS-induced release of IL-1β, IL-6 and/or IL-8 from monocytes by measuring concentrations of IL-1β, IL-6 and/or IL-8 by methods well known to those skilled in the art. In a similar manner to the above described assay involving the LPS induced release of TNF-α from monocytes, compounds of this invention can also be shown to inhibit LPS induced release of IL-1β, IL-6 and/or IL-8 from monocytes by measuring concentrations of IL-1β, IL-6 and/or IL-8 by methods well known to those skilled in the art. Thus, the compounds of the invention may lower elevated levels of TNF-α, IL-1, IL-6, and IL-8 levels. Reducing elevated levels of these inflammatory cytokines to basal levels or below is favorable in controlling, slowing progression, and alleviating many disease states. All of the compounds are useful in the methods of treating disease states in which TNF-α, IL-1β, IL-6, and IL-8 play a role to the full extent of the definition of TNF-α-mediated diseases described herein.

Inhibition of LPS-Induced TNF-α production in mice

Male DBA/1LACJ mice are dosed with vehicle or test compounds in a vehicle (the vehicle consisting of 0.5% tragacanth in 0.03 N HCl) 30 minutes prior to lipopolysaccharide (2 mg/kg, I.V.) injection. Ninety minutes after LPS injection, blood are collected and the serum is analyzed by ELISA for TNF levels.

Selected compounds from the class have shown in vivo activity in a LPS mouse model in which serum levels of TNF-α were reduced in the presence of compounds of this invention.

Compounds of the invention may be shown to have anti-inflammatory properties in animal models of inflammation, including carageenan paw edema, collagen induced arthritis and adjuvant arthritis, such as the carageenan paw edema model (C. A. Winter et al Proc. Soc. Exp. Biol. Med. (1962) vol 111, p 544; K. F. Swingle, in R. A. Scherrer and M. W. Whitehouse, Eds., Antiinflammatory Agents, Chemistry and Pharmacology, Vol. 13-II, Academic, N.Y., 1974, p. 33) and collagen induced arthritis (D. E. Trentham et al J. Exp. Med. (1977) vol. 146, p 857; J. S. Courtenay, Nature (New Biol.) (1980), Vol 283, p 666).

125 I-Glucagon Binding Screen with CHO/hGLUR Cells

The assay is described in WO 97/16442, which is incorporated herein by reference in its entirety.

Reagents

The reagents can be prepared as follows: (a) prepare fresh 1M o-Phenanthroline (Aldrich) (198.2 mg/ml ethanol); (b) prepare fresh 0.5M DTT (Sigma); (c) Protease Inhibitor Mix (1000X): 5 mg leupeptin, 10 mg benzamidine, 40 mg bacitracin and 5 mg soybean trypsin inhibitor per ml DMSO and store aliquots at −20° C.; (d) 250 μM human glucagon (Peninsula): solubilize 0.5 mg vial in 575 μl 0.1N acetic acid (1 μl yields 1 μM final concentration in assay for non-specific binding) and store in aliquots at −20° C.; (e) Assay Buffer: 20 mM Tris (pH 7.8), 1 mM DTT and 3 mM o-phenanthroline; (f) Assay Buffer with 0.1% BSA (for dilution of label only; 0.01% final in assay): 10 μl 10% BSA (heat-inactivated) and 990 μl Assay Buffer; (g) 125 I-Glucagon (NEN, receptor-grade, 2200 Ci/mmol): dilute to 50,000 cpm/25 μl in assay buffer with BSA (about 50pM final concentration in assay).

Harvesting of CHO/hGLUR Cells for Assay

1. Remove media from confluent flask then rinse once each with PBS (Ca, Mg-free) and Enzyme-free Dissociation Fluid (Specialty Media, Inc.).

2. Add 10 ml Enxyme-free Dissoc. Fluid and hold for about 4 min. at 37° C.

3. Gently tap cells free, triturate, take aliquot for counting and centrifuge remainder for 5 min. at 1000 rpm.

4. Resuspend pellet in Assay Buffer at 75000 cells per 100 μl.

Membrane preparations of CHO/hGLUR cells can be used in place of whole cells at the same assay volume. Final protein concentration of a membrane preparation is determined on a per batch basis.

Assay

The determination of inhibition of glucagon binding can be carried out by measuring the reduction of I 125 -glucagon binding in the presence of compounds of Formula I. The reagents are combined in 120 μL of assay buffer as follows:

	Compound/	250 μM	125 I-	CHO/hGLUR
	Vehicle	Glucagon	Glucagon	Cells
Total	—/5 μl	—	25 μl	100 μl
Binding
+	5 μl/—	—	25 μl	100 μl
Compound
Non-	—/5 μl	1 μl	25 μl	100 μl
specific
Binding

The mixture is incubated for 60 min. at 22° C. on a shaker at 275 rpm. The mixture is filtered over pre-soaked (0.5% polyethylimine (PEI)) GF/C filtermat using an Innotech Harvester or Tomtec Harvester with four washes of ice-cold 20 mM Tris buffer (pH 7.8). The radioactivity in the filters is determined by a gamma-scintillation counter.

Thus, compounds of the invention may also be shown to inhibit the binding of glucagon to glucagon receptors.

Cyclooxygenase Enzyme Activity Assay

The human monocytic leukemia cell line, THP-1, differentiated by exposure to phorbol esters expresses only COX-1; the human osteosarcoma cell line 143B expresses predominantly COX-2. THP-1 cells are routinely cultured in RPMI complete media supplemented with 10% FBS and human osteosarcoma cells (HOSC) are cultured in minimal essential media supplemented with 10% fetal bovine serum (MEM-10%FBS); all cell incubations are at 37° C. in a humidified environment containing 5% CO 2 .

COS-1 Assay

In preparation for the COX-1 assay. THP-1 cells are grown to confluency, split 1:3 into RPMI containing 2% FBS and 10 mM phorbol 12-myristate 13-acetate (TPA), and incubated for 48 hours on a shaker to prevent attachment. Cells are pelleted and resuspended in Hank's Buffered Saline (HBS) at a concentration of 2.5×10 6 cells/mL and plated in 96-well culture plates at a density of 5×10 5 cells/mL. Test compounds are diluted in HBS and added to the desired final concentration and the cells are incubated for an additional 4 hours. Arachidonic acid is added to a final concentration of 30 mM, the cells incubated for 20 minutes at 37° C., and enzyme activity determined as described below.

COX-2 Assay

For the COX-2 assay, subconfluent HOSC are trypsinized and resuspended at 3×10 6 cells/mL in MEM-FBS containing 1 ng human IL-1b/mL, plated in 96-well tissue culture plates at a density of 3×10 4 cells per well, incubated on a shaker for 1 hour to evenly distribute cells, followed by an additional 2 hour static incubation to allow attachment. The media is then replaced with MEM containing 2% FBS (MEM-2%FBS) and 1 ng human IL-1b/mL, and the cells incubated for 18-22 hours. Following replacement of media with 190 ml MEM, 10 mL of test compound diluted in HBS is added to achieve the desired concentration and the cells incubated for 4 hours. The supernatants are removed and replaced with MEM containing 30 mM arachidonic acid, the cells incubated for 20 minutes at 37° C., and enzyme activity determined as described below.

COX Activity Determined

After incubation with archidonic acid, the reactions are stopped by the addition of 1 N HCl, followed by neutralization with 1 N NaOH and centrifugation to pellet cell debris. Cyclooxygenase enzyme activity in both HOSC and THP-1 cell supernatants is determined by measuring the concentration of PGE 2 using a commercially available ELISA (Neogen #404110). A standard curve of PGE 2 is used for calibration, and commercially available COX-1 and COX-2 inhibitors are included as standard controls.

The following compound exhibits activities in the Cyclooxygenase assay with IC 50 values of 10 μM or less: 2-(2,4-dimethylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine.

Raf Kinase assay

In vitro Raf kinase activity is measured by the extent of phosphorylation of the substrate MEK (Map kinase/ERK kinase) by activated Raf kinase. Phosphorylated MEK is trapped on a filter and incorporation of radiolabeled phosphate is quantified by scintillation counting.

MATERIALS:

Activated Raf is produced by triple transfection of Sf9 cells with baculoviruses expressing “Glu-Glu”-epitope tagged Raf,val 12 -H-Ras, and Lck. The “Glu-Glu”-epitope, Glu-Try-Met-Pro-Met-Glu, was fused to the carboxy-terminus of full length c-Raf.

Catalytically inactive MEK (K97A mutation) is produced in Sf9 cells transfected with a baculovirus expressing c-terminus “Glu-Glu” epitope-tagged K97A MEK1.

Anti “Glu-Glu” antibody was purified from cells grown as described in: Grussenmeyer, et al., Proceedings of the National Academy of Science, U.S.A. pp 7952-7954, 1985.

Column buffer: 20 mM Tris pH=8, 100 mM NaCl, 1 mM EDTA, 2.5 mM EGTA, 10 mM MgCl 2 , 2 mM DTT, 0.4 mM AEBSF, 0.1% n-octylglucopyranoside, 1 nM okadeic acid, and 10 μg/mL each of benzamidine, leupeptin, pepstatin, and aproptinin.

5x Reaction buffer: 125 mM HEPES pH=8, 25 mM MgCl 2 , 5 mM EDTA, 5 mM Na 3 VO 4 , 100 μg/mL BSA.

Enzyme dilution buffer: 25 mM HEPES pH=8, 1 mM EDTA, 1 mM Na 3 VO 4 , 400 μg/mL BSA.

Stop solution: 100 mM EDTA, 80 mM sodium pyrophosphate.

Filter plates: Milipore multiscreen #SE3MO78E3, Immobilon-P (PVDF).

METHODS:

Protein purification: Sf9 cells were infected with baculovirus and grown as described in Williams, et al., Proceedings of the National Academy of science, U.S.A. pp 2922-2926, 1992. All subsequent steps were preformed on ice or at 4° C. Cells were pelleted and lysed by sonication in column buffer. Lysates were spun at 17,000xg for 20 min, followed by 0.22 μm filtration. Epitope tagged proteins were purified by chromatography over GammaBind Plus affinity column to which the “Glu-Glu” antibody was coupled. Proteins were loaded on the column followed by sequential washes with two column volumes of column buffer, and eluted with 50 μg/mL Glu-Tyr-Met-Pro-Met-Glu in column buffer.

Raf kinase assay: Test compounds were evaluated using ten 3-fold serial dilutions starting at 10-100 μM. 10 μL of the test inhibitor or control, dissolved in 10% DMSO, was added to the assay plate followed by the addition of 30 μL of the a mixture containing 10 μL 5x reaction buffer, 1 mM 33 P-γ-ATP (20 μCi/mL), 0.5 μL MEK (2.5 mg/mL), 1 μL 50 mM β-mercaptoethanol. The reaction was started by the addition of 10 μL of enzyme dilution buffer containing 1 mM DTT and an amount of activated Raf that produces linear kinetics over the reaction time course. The reaction was mixed and incubated at room temperature for 90 min. and stopped by the addition of 50 μL stop solution. 90 μL aliquots of this stopped solution were transferred onto GFP-30 cellulose microtiter filter plates (Polyfiltronics), the filter plates washed in four well volumes of 5% phosphoric acid, allowed to dry, and then replenished with 25 μl scintillation cocktail. The plates were counted for 33 P gamma emission using a TopCount Scintillation Reader.

Accordingly, the compounds of the invention or a pharmaceutical composition thereof are useful for prophylaxis and treatment of rheumatoid arthritis; Pagets disease; osteophorosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; pancreatic β cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; asthma; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption diseases; graft vs. host reaction; ischemia reperfusion injury; atherosclerosis; brain trauma; Alzheimer's disease; stroke; myocardial infarction; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection. HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses (including HSV-1, HSV-2), and herpes zoster, all of which are sensitive to TNF-α and/or IL-1 inhibition or glucagon antagonism, will also be positively effected by the compounds and methods of the invention.

The compounds of the present invention may also possess oncolytic characteristics and may be useful for the treatment of cancer. The compounds of the present invention may also block signal transduction by extracellular mitogenic stimuli and oncoproteins through inhibition of Raf kinase.

The compounds of the present invention also may possess analgesic properties and may be useful for the treatment of pain disorders, such as hyperalgesia due to excessive IL-1. The compounds of the present invention may also prevent the production of prostaglandins by inhibition of enzymes in the human arachidonic acid/prostaglandin pathway, including cyclooxygenase (WO 96/03387, incorporated herein by reference in its entirety).

Because of their ability to lower TNF-α and IL-1 concentrations or inhibit glucagon binding to its receptor, the compounds of the invention are also useful research tools for studying the physiology associated with blocking these effects.

The methods of the invention comprise administering an effective dose of a compound of the invention, a pharmaceutical salt thereof, or a pharmaceutical composition of either, to a subject (i.e., an animal, preferably a mammal, most preferably a human) in need of a reduction in the level of TNF-α, IL-1, IL-6, and/or IL-8 levels and/or reduction in plasma glucose levels and/or which subject may be suffering from rheumatoid arthritis; Pagets disease; osteophorosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; pancreatic β cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; asthma; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; cancer; bone resorption diseases; graft vs. host reaction; Alzheimer's disease; stroke; myocardial infarction; ischemia reperfusion injury; atherosclerosis; brain trauma; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection, or which subject is infected by HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses (including HSV-1, HSV-2), or herpes zoster.

In another aspect, this invention comprises the use of a compound of the invention, or pharmaceutically acceptable salts thereof, in the manufacture of a medicament for the treatment either acutely or chronically of a TNF-α, IL-1β, IL-6, and/or IL-8 mediated disease state, including those described previously. The compounds of the present are also useful in the manufacture of an anti-cancer medicant. The compounds of the present invention are also useful in the manufacture of a medicant to attenuate or prevent signal transduction by extracellular mitogenic stimuli and oncoproteins through inhibition of Raf kinase. Also, the compounds of this invention are useful in the manufacture of a analgesic medicament and a medicament for treating pain disorders, such as hyperalgesia. The compounds of the present invention also are useful in the manufacture of a medicament to prevent the production of prostaglandins by inhibition of enzymes in the human arachiodonic acid/prostaglandin pathway.

In still another aspect, this invention provides a pharmaceutical composition comprising an effective TNF-α, IL-1β, IL-6, and/or IL-8 lowering amount and/or effective plasma glucose level lowering amount, and/or effective tumor supressing amount of a compound of the invention and a pharmaceutically acceptable carrier or diluent, and if desired other active ingredients. The compounds of the invention are administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended. Therapeutically effective doses of the compounds of the present invention required to arrest the progress or prevent tissue damage associated with the disease are readily ascertained by one of ordinary skill in the art using standard methods.

For the treatment of TNF-α, IL-1β, IL-6, and IL-8 mediated diseases, cancer, and/or hyperglycemia, the compounds of the present invention may be administered orally, parentally, by inhalation spray, rectally, or topically in dose unit formulations containing conventional pharmaceutically acceptable carriers, adjuvants, and vehicles. The term parenteral as used herein includes, subcutaneous, intravenous, intramuscular, intrasternal, infusion techniques or intraperitoneally.

The dosage regimen for treating a TNF-α, IL-1, IL-6, and IL-8 mediated diseases, cancer, and/or hyperglycemia with the compounds of this invention and/or compositions of this invention is based on a variety of factors, including the type of disease, the age, weight, sex, medical condition of the patient, the severity of the condition, the route of administration, and the particular compound employed. Thus, the dosage regime may vary widely, but can be determined routinely using standard methods. Dosage levels of the order from about 0.01 mg to 30 mg per kilogram of body weight per day, preferably from about 0.1 mg to 10 mg/kg, more preferably from about 0.25 mg to 1 mg/kg are useful for all methods of use disclosed herein.

The pharmaceutically active compounds of this invention can be processed in accordance with conventional methods of pharmacy to produce medicinal agents for administration to patients, including humans and other mammals.

For oral administration, the pharmaceutical composition may be in the form of, for example, a capsule, a tablet, a suspension, or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a given amount of the active ingredient. For example, these may contain an amount of active ingredient from about 1 to 2000 mg, preferably from about 1 to 500 mg, more preferably from about 5 to 150 mg. A suitable daily dose for a human or other mammal may vary widely depending on the condition of the patient and other factors, but, once again, can be determined using routine methods.

The active ingredient may also be administered by injection as a composition with suitable carriers including saline, dextrose, or water. The daily parenteral dosage regimen will be from about 0.1 to about 30 mg/kg of total body weight, preferably from about 0.1 to about 10 mg/kg, and more preferably from about 0.25 mg to 1 mg/kg.

Injectable preparations, such as sterile injectable aqueous or oleaginous suspensions, may be formulated according to the known are using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed, including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable non-irritating excipient such as cocoa butter and polyethylene glycols that are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drug.

A suitable topical dose of active ingredient of a compound of the invention is 0.1 mg to 150 mg administered on to four, preferably one or two times daily. For topical administration, the active ingredient may comprise from 0.001% to 10% w/w, e.g., from 1% to 2% by weight of the formulation, although it may comprise as much as 10% w/w, but preferably not more than 5% w/w, and more preferably from 0.1% to 1% of the formulation.

Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin (e.g., liniments, lotions, ointments, creams, or pastes) and drops suitable for administration to the eye, ear, or nose.

For administration, the compounds of this invention are ordinarily combined with one or more adjuvants appropriate for the indicated route of administration. The compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, stearic acid, talc, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulphuric acids, acacia, gelatin, sodium alginate, polyvinylpyrrolidine, and/or polyvinyl alcohol, and tableted or encapsulated for conventional administration. Alternatively, the compounds of this invention may be dissolved in saline, water, polyethylene glycol, propylene glycol, ethanol, corn oil, peanut oil, cottonseed oil, sesame oil, tragacanth gum, and/or various buffers. Other adjuvants and modes of administration are well known in the pharmaceutical art. The carrier or diluent may include time delay material, such as glyceryl monostearate or glyceryl distearate alone or with a wax, or other materials well known in the art.

The pharmaceutical compositions may be made up in a solid form (including granules, powders or suppositories) or in a liquid form (e.g., solutions, suspensions, or emulsions). The pharmaceutical compositions may be subjected to conventional pharmaceutical operations such as sterilization and/or may contain conventional adjuvants, such as preservatives, stabilizers, wetting agents, emulsifiers, buffers etc.

Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting, sweetening, flavoring, and perfuming agents.

Compounds of the present invention can possess one or more asymmetric carbon atoms and are thus capable of existing in the form of optical isomers as well as in the form of racemic or non-racemic mixtures thereof. The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processes, e.g., by formation of diastereoisomeric salts, by treatment with an optically active acid or base. Examples of appropriate acids are tartaric, diacetyltartaric, dibenzoyltartaric, ditoluoyltartaric, and camphorsulfonic acid and then separation of the mixture of diastereoisomers by crystallization followed by liberation of the optically active bases from these salts. A different process for separation of optical isomers involves the use of a chiral chromatography column optimally chosen to maximize the separation of the enantiomers. Still another available method involves synthesis of covalent diastereoisomeric molecules by reacting compounds of the invention with an optically pure acid in an activated form or an optically pure isocyanate. The synthesized diastereoisomers can be separated by conventional means such as chromatography, distillation, crystallization or sublimation, and then hydrolyzed to deliver the enantiomerically pure compound. The optically active compounds of the invention can likewise be obtained by using active starting materials. These isomers may be in the form of a free acid, a free base, an ester or a salt.

The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. The salts include, but are not limited to, the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, methansulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 2-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, mesylate, and undecanoate. Also, the basic nitrogen-containing groups can be quaternized with such agents as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chloride, bromides and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl bromides, and others. Water or oil-soluble or dispersible products are thereby obtained.

Examples of acids that may be employed to from pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. Other examples include salts with alkali metals or alkaline earth metals, such as sodium, potassium, calcium or magnesium or with organic bases.

While the compounds of the invention can be administered as the sole active pharmaceutical agent, they can also be used in combination with one or more compounds of the invention or other agents. When administered as a combination, the therapeutic agents can be formulated as separate compositions that are given at the same time or different times, or the therapeutic agents can be given as a single composition.

The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds. Variations and changes which are obvious to one skilled in the art are intended to be within the scope and nature of the invention which are defined in the appended claims.

From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

Claims

1. A compound of the formula or a pharmaceutically acceptable salt thereof, whereinX is O, S, S(O), S(O)2 or NR2; Y is —C(O)—NR3R4 or —NR4—C(O)—R3; R1 is a heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R18—Z18— or R18—Z18—alkyl; provided that R1 is other than an optionally substituted pyridyl radical; and provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R1 is 1-3; and provided when Y is —NR4—C(O)—R3 and X is O or S, R1 is other than a 2-pyrimidinyl radical; R2 is a hydrogen or alkyl radical; R3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals or alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R19—Z19— or R19—Z19—alkyl; provided that the total number of aryl and heteroaryl radicals in R3 is 1-3; and provided when Y is —C(O)—NR3R4, R3 is other than a phenyl or naphthyl having an amino, nitro, cyano, carboxy or alkoxycarbonyl substituent bonded to the ring carbon atom adjacent to the ring carbon atom bonded to —NR4—; and R4 is a hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl or R20—Z20—alkyl radical; wherein R18, R19 and R20 are each independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical; wherein the aryl and heteroaryl radicals of R4, R18, R19 and R20 are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy; and Z18, Z19 and Z20 are each independently —O—, —S—, —S(O)—, —S(O)2—, —CO2—, —C(O)—, —NR21—, —NR21—C(O)—, —C(O)—NR21—, —NR21—S(O)2— or —S(O)2—NR21—; wherein each R21 is independently a hydrogen or alkyl radical; R5 and R6 are each independently a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical; and R7 is a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, whereinR1 is a heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C1-C6 alkyl, halo, C1-C6 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R18—Z18— or R18—Z18—C1-C6 alkyl; provided that R1 is other than an optionally substituted pyridyl radical; and provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R1 is 1-3; and provided when Y is —NR4—C(O)—R3 and X is O or S, R1 is other than a 2-pyrimidinyl radical; R2 is a hydrogen or C1-C4 alkyl radical; R3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C1-C6 alkyl, halo, C1-C6 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R19—Z19— or R19—Z19—C1-C6 alkyl; provided that the total number of aryl and heteroaryl radicals in R3 is 1-3; and provided when Y is —C(O)—NR3R4, R3 is other than a phenyl or naphthyl having an amino, nitro, cyano, carboxy or alkoxycarbonyl substituent bonded to the ring carbon atom adjacent to the ring carbon atom bonded to —NR4—; and R4 is a radical of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl of 1-3 halo radicals, C2-C6 haloalkenyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C1-C4 alkyl, heteroaryl-C1-C4 alkyl or R20—Z20—C1-C6 alkyl radical; and wherein R18, R19 and R20 are each independently a hydrogen, C1-C4 alkyl, C1-C4 haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C1-C4 alkyl or heteroaryl-C1-C4 alkyl radical; wherein the aryl and heteroaryl radicals of R4, R18, R19 and R20 are optionally substituted by 1-3 radicals of hydroxy, C1-C4 alkoxy, C1-C4 alkylthiol, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, C1-C5 alkanoylamino, C1-C4 alkylsulfonylamino, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, (C1-C4 alkoxy)carbonylamino, (C1-C4 alkoxy)carbonyl, cyano, halo, azido, C1-C4 alkyl, C1-C4 haloalkyl of 1-3 halo radicals or C1-C4 haloalkoxy of 1-3 halo radicals; and each R21 is independently a hydrogen or C1-C4 alkyl radical; R5 and R6 are each independently a hydrogen, C1-C4 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, C1-C4 haloalkoxy of 1-3 halo radicals, C1-C4 aminoalkyl, (C1-C4 alkyl)amino-C1-C4 alkyl, di(C1-C4 alkyl)amino-C1-C4 alkyl, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, C1-C5 alkanoylamino, C1-C4 alkylsulfonylamino, aminosulfonyl, C1-C4 alkylaminosulfonyl, di(C1-C4 alkyl)aminosulfonyl, hydroxy, C1-C4 hydroxyalkyl, thiol, C1-C4 alkylthiol, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkoxy, (C1-C4 alkoxy)C1-C4 alkyl, cyano, azido, nitro, carboxy, (C1-C4 alkoxy)carbonyl, aminocarbonyl, (C1-C4 alkyl)aminocarbonyl or di(C1-C4 alkyl)aminocarbonyl radical; and R7 is a hydrogen, C1-C4 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, C1-C4 haloalkoxy of 1-3 halo radicals, C1-C4 aminoalkyl, (C1-C4 alkyl)amino-C1-C4 alkyl, di(C1-C4 alkyl)amino-C1-C4 alkyl, aminosulfonyl, C1-C4 alkylaminosulfonyl, di(C1-C4 alkyl)aminosulfonyl, hydroxy, C1-C4 hydroxyalkyl, thiol, C1-C4 alkylthiol, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkoxy, (C1-C4 alkoxy)C1-C4 alkyl, cyano, azido, nitro, carboxy, (C1-C4 alkoxy)carbonyl, aminocarbonyl, (C1-C4 alkyl)aminocarbonyl or di(C1-C4 alkyl)aminocarbonyl radical; and wherein cycloalkyl is a monocyclic, bicyclic or tricyclic carbocyclic alkyl radical of 5-12 ring members, which is optionally partially unsaturated, benzo fused or heterocyclo fused; aryl is a phenyl or biphenyl radical which is optionally benzo fused or heterocyclo fused; heterocyclyl is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals; and heteroaryl is a monocyclic or bicyclic aromatic heterocyclic ring system having 5-6 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally benzo-fused or saturated C3-C4-carbocyclic-fused.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein Y is —NR4—C(O)—R3.

4. The compound of claim 3 or a pharmaceutically acceptable salt thereof, whereinX is O or NR2; R1 is a heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C1-C4 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R18—Z18— or R18—Z18—C1-C4 alkyl; provided that R1 is other than an optionally substituted pyridyl radical; and provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R1 is 1-2; wherein each R18 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C2 alkyl or heteroaryl-C1-C2 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C1-C4 alkoxy, C1-C4 alkylthiol, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, acetylamino, cyano, halo, azido, C1-C4 alkyl, trifluoromethyl or trifluoromethoxy; and R2 is a hydrogen or C1-C2 alkyl radical; R3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C1-C6 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R19—Z19— or R19—Z19—C1-C4 alkyl; provided that the total number of aryl and heteroaryl radicals in R3 is 1-2; and wherein each R19 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C4 alkyl or heteroaryl-C1-C4 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C1-C4 alkoxy, C1-C4 alkylthiol, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, acetylamino, cyano, halo, C1-C4 alkyl, trifluoromethyl or trifluoromethoxy; and R4 is a radical of hydrogen, C1-C6 alkyl, aryl, heteroaryl, aryl-C1-C4 alkyl, heteroaryl-C1-C4 alkyl or R20—Z20—C2-C4 alkyl radical; and wherein R20 is a hydrogen, C1-C4 alkyl, aryl, heteroaryl, aryl-C1-C2 alkyl or heteroaryl-C1-C2 alkyl radical; wherein the aryl and heteroaryl radicals of R4 and R20 are optionally substituted by 1-2 radicals of hydroxy, C1-C4 alkoxy, C1-C4 alkylthiol, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, acetylamino, halo, C1-C4 alkyl, trifluoromethyl or trifluoromethoxy; and Z20 is —O— or —NR21—; wherein each R21 is independently a hydrogen or methyl radical; R5 and R6 are each independently a hydrogen, C1-C4 alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, C1-C5 alkanoylamino, hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkoxy, cyano, azido, nitro, carboxy, (C1-C4 alkoxy)carbonyl, aminocarbonyl, (C1-C4 alkyl)aminocarbonyl or di(C1-C4 alkyl)aminocarbonyl radical; and R7 is a hydrogen, C1-C4 alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkoxy, carboxy, (C1-C4 alkoxy)carbonyl, aminocarbonyl, (C1-C4 alkyl)aminocarbonyl or di(C1-C4 alkyl)aminocarbonyl radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-12 ring members, which is optionally partially unsaturated, benzo fused or heterocyclo fused; aryl is a phenyl or biphenyl radical which is optionally benzo fused or heterocyclo fused; heterocyclyl is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals; and heteroaryl is a monocyclic aromatic heterocyclic ring system having 5-6 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally benzo-fused or saturated C3-C4-carbocyclic-fused.

5. The compound of claim 4 or a pharmaceutically acceptable salt thereof, whereinR3 is a radical of the formula whereinU is C—R13 or N; V and W are each independently C—R12 or N; R11 and R13 are each independently a radical of hydrogen, C1-C4 alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R19—Z19—; and each R12 is independently a radical of hydrogen, C1-C6 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, R31—Z31— or R31—Z31—C1-C4 alkyl; provided that the combined total number of aryl and heteroaryl radicals in R11, R12 and R13 is 0-1; wherein each R19 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C4 alkyl or heteroaryl-C1-C4 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z19 is independently —O—, —S(O)2—, —CO2—, —C(O)—, —NR21—C(O)—, —C(O)—NR21—, —NR21—S(O)2— or —S(O)2—NR21—; wherein each R31 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C4 alkyl or heteroaryl-C1-C4 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z31 is independently —O—, —NR21—, —NR21—C(O)—, —C(O)—NR21—, —NR21—S(O)2— or —S(O)2—NR21—; wherein R4 is a radical of hydrogen, C1-C6 alkyl, aryl, heteroaryl, aryl-C1-C4 alkyl, heteroaryl-C1-C4 alkyl or R20—Z20—C2-C4 alkyl radical; wherein R20 is a hydrogen, C1-C4 alkyl, aryl, heteroaryl, aryl-C1-C2 alkyl or heteroaryl-C1-C2 alkyl radical; wherein the aryl and heteroaryl radicals of R4 and R20 are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and R5 and R6 are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C1-C2 alkylamino, di(C1-C2 alkyl)amino, hydroxy, methoxy or ethoxy radical; and R7 is a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, methoxy or ethoxy radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-10 ring members, which is optionally partially unsaturated with one double bond, benzo fused or heterocyclo fused; aryl is a phenyl or biphenyl radical which is optionally benzo fused or heterocyclo fused; heterocyclyl is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals; and heteroaryl is a monocyclic aromatic heterocyclic ring system having 5-6 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally benzo-fused or saturated C3-C4-carbocyclic-fused.

6. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein Y is —C(O)—NR3R4.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, whereinX is O or NR2; R1 is a heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C1-C4 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R18—Z18— or R18—Z18—C1-C4 alkyl; provided that R1 is other than an optionally substituted pyridyl radical; and provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R1 is 1-2; wherein each R18 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C2 alkyl or heteroaryl-C1-C2 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C1-C4 alkoxy, C1-C4 alkylthiol, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, acetylamino, cyano, halo, azido, C1-C4 alkyl, trifluoromethyl or trifluoromethoxy; and each Z18 is independently —O—, —S—, —S(O)—, —S(O)2—, —CO2—, —C(O)—, —NR21—, —NR21—C(O)—, —C(O)—NR21—, —NR21—S(O)2— or —S(O)2—NR21—; wherein each R21 is independently a hydrogen or C1-C4 alkyl radical; R2 is a hydrogen or C1-C2 alkyl radical; R3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C1-C6 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R19—Z19— or R19—Z19—C1-C4 alkyl; provided that the total number of aryl and heteroaryl radicals in R3 is 1-2; and provided R3 is other than a phenyl or naphthyl having an amino, nitro, cyano, carboxy or alkoxycarbonyl substituent bonded to the ring carbon atom adjacent to the ring carbon atom bonded to —NR4—; and wherein each R19 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C4 alkyl or heteroaryl-C1-C4 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C1-C4 alkoxy, C1-C4 alkylthiol, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, acetylamino, cyano, halo, C1-C4 alkyl, trifluoromethyl or trifluoromethoxy; and R4 is a radical of hydrogen, C1-C6 alkyl, aryl, heteroaryl, aryl-C1-C4 alkyl, heteroaryl-C1-C4 alkyl or R20—Z20—C2-C4 alkyl radical; and wherein R20 is a hydrogen, C1-C4 alkyl, aryl, heteroaryl, aryl-C1-C2 alkyl or heteroaryl-C1-C2 alkyl radical; wherein the aryl and heteroaryl radicals of R4 and R20 are optionally substituted by 1-2 radicals of hydroxy, C1-C4 alkoxy, C1-C4 alkylthiol, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, acetylamino, halo, C1-C4 alkyl, trifluoromethyl or trifluoromethoxy; and Z20 is —O— or —NR21—; wherein each R21 is independently a hydrogen or methyl radical; R5 and R6 are each independently a hydrogen, C1-C4 alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, C1-C5 alkanoylamino, hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkoxy, cyano, azido, nitro, carboxy, (C1-C4 alkoxy)carbonyl, aminocarbonyl, (C1-C4 alkyl)aminocarbonyl or di(C1-C4 alkyl)aminocarbonyl radical; and R7 is a hydrogen, C1-C4 alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkoxy, carboxy, (C1-C4 alkoxy)carbonyl, aminocarbonyl, (C1-C4 alkyl)aminocarbonyl or di(C1-C4 alkyl)aminocarbonyl radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-12 ring members, which is optionally partially unsaturated, benzo fused or heterocyclo fused; aryl is a phenyl or biphenyl radical which is optionally benzo fused or heterocyclo fused; heterocyclyl is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals; and heteroaryl is a monocyclic aromatic heterocyclic ring system having 5-6 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally benzo-fused or saturated C3-C4-carbocyclic-fused.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, whereinR3 is a radical of the formula whereinU is C—R13 or N; V and W are each independently C—R12 or N; R11 and R13 are each independently a radical of hydrogen, C1-C4 alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R19—Z19—; and each R12 is independently a radical of hydrogen, C1-C6 alkyl, halo, C1-C4 haloalkyl of 1-3 halo radicals, R31—Z31— or R31—Z31—C1-C4 alkyl; provided that the combined total number of aryl and heteroaryl radicals in R11, R12 and R13 is 0-1; provided when U is C—R13 and V and W are each C—R12, R11 and R13 are each other than a nitro, cyano, carboxy or alkoxycarbonyl radical; wherein each R19 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C4 alkyl or heteroaryl-C1-C4 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z19 is independently —O—, —S(O)2—, —CO2—, —C(O)—, —NR21—C(O)—, —C(O)—NR21—, —NR21—S(O)2— or —S(O)2—NR21—; wherein each R21 is independently a hydrogen or methyl radical; wherein each R31 is independently a hydrogen, C1-C4 alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C1-C4 alkyl or heteroaryl-C1-C4 alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, acetylamino, cyano, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and each Z31 is independently —O—, —NR21—, —NR21—C(O)—, —C(O)—NR21—, —NR21—S(O)2— or —S(O)2—NR21—; R4 is a radical of hydrogen, C1-C6 alkyl, aryl, heteroaryl, aryl-C1-C4 alkyl, heteroaryl-C1-C4 alkyl or R20—Z20—C2-C4 alkyl radical; and wherein R20 is a hydrogen, C1-C4 alkyl, aryl, heteroaryl, aryl-C1-C2 alkyl or heteroaryl-C1-C2 alkyl radical; wherein the aryl and heteroaryl radicals of R4 and R20 are optionally substituted by 1-2 radicals of hydroxy, methoxy, ethoxy, methylthiol, ethylthiol, amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, halo, methyl, ethyl, trifluoromethyl or trifluoromethoxy; and R5 and R6 are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C1-C2 alkylamino, di(C1-C2 alkyl)amino, hydroxy, methoxy or ethoxy radical; and R7 is a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, methoxy or ethoxy radical; and wherein cycloalkyl is a monocyclic or bicyclic carbocyclic alkyl radical of 5-10 ring members, which is optionally partially unsaturated with one double bond, benzo fused or heterocyclo fused; aryl is a phenyl or biphenyl radical which is optionally benzo fused or heterocyclo fused; heterocyclyl is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals; and heteroaryl is a monocyclic aromatic heterocyclic ring system having 5-6 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally benzo-fused or saturated C3-C4-carbocyclic-fused.

9. A pharmaceutical composition comprising a compound of any one of claims 1-8 and a pharmaceutically acceptable carrier.

10. A method for prophylaxis or treatment of inflammation comprising administering an effective amount of a compound of any one of claims 1-8.

11. A method for prophylaxis or treatment of inflammation comprising administering an effective amount of a composition of claim 9.