US20020035094A1

US20020035094A1 - Substituted pyridine compounds and methods of use

Info

Publication number: US20020035094A1
Application number: US09/932,281
Authority: US
Inventors: Nathan Mantlo; Stephen Schlachter; John Josey
Original assignee: Amgen Inc
Current assignee: Amgen Inc
Priority date: 1997-11-07
Filing date: 2001-08-17
Publication date: 2002-03-21
Anticipated expiration: 2018-11-03
Also published as: US6184237B1; AU1306599A; DE69838070D1; EP1028945B1; DE69838070T2; WO1999024404A1; US6333341B1; EP1028945A1; EP1028945B9; US6458813B1; ES2290997T3; JP2001522834A; CA2307552A1; CA2307552C; AU742442B2; ATE366722T1; US6022884A

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 a (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, 1994; 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-a 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-a 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 97/18626; 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 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. 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, R⁵, R⁶, R⁷, 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) ₂or NR²; preferably, X is O, S or NR²; more preferably, X is O or NR²; most preferably, X is NR²;

Y is —C(O)—NR ³R⁴or —NR⁴—C(O)—R³;

R ¹is a cycloalkyl, aryl, 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;

preferably, R ¹is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C₁-C₆alkyl, halo, C₁-C₆haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸—Z¹⁸— or R¹⁸—Z¹⁸—C₁-C₆alkyl;

more preferably, R is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C ₁-C₄alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸—Z¹⁸— or R¹⁸—Z¹⁸—C₁-C₄alkyl;

provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R ¹is 1-3, preferably, 1-2, and provided when Y is —NR⁴—C(O)—R³and X is O or S, R¹is other than a 2-pyrimidinyl radical;

more preferably, R ¹is a radical of the formula

wherein R ²², R²³, R²⁴, R²⁵and R²⁶are each independently a radical of hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁸—Z¹⁸— or R¹⁸—Z¹⁸—C₁-C₄alkyl; provided at least one of R²¹, R²², R²³, R²⁴and R²⁵is hydrogen; and provided that the combined total number of aryl and heteroaryl radicals in R²², R²³, R²⁴, R²⁵and R²⁶is 0-1;

R ²is a hydrogen or alkyl radical; preferably, R²is a hydrogen or C₁-C₄alkyl radical; more preferably, R²is a hydrogen or C₁-C₂alkyl radical; more preferably, R²is a hydrogen or methyl radical; and most: preferably, R²is a hydrogen radical;

R ³is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R¹⁹—Z¹⁹— or R¹⁹—Z¹⁹-alkyl; preferably, R³is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C₁-C₆alkyl, halo, C₁-C₆haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹—Z¹⁹— or R¹⁹—Z¹⁹—C₁-C₆alkyl; more preferably, R³is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C₁-C₆alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹—Z¹⁹— or R¹⁹—Z¹⁹—C₁-C₄alkyl;

provided that the total number of aryl and heteroaryl radicals in R ³is 1-3, preferably, 1-2; and provided when Y is —C(O)—NR³R⁴, R³is 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—;

more preferably, R ³is a radical of the formula

wherein

U is C—R ¹³or N;

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

R ¹¹and R¹³are each independently a radical of hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R¹⁹—Z¹⁹—; preferably, R¹¹and R¹³are each independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁹—O—, R¹⁹—S(O)₂—, R¹⁹—O—C(O)—, R¹⁹C(O)—, R¹⁹—NR²¹—C(O)— or R¹⁹—NR²¹—S(O)₂—;

each R ¹²is independently a radical of hydrogen, C₁-C₆alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, R³¹—Z³¹— or R³¹—Z³¹—C₁-C₄alkyl; preferably, each R¹²is 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, R¹²and R¹³is 0-1;

wherein each R ³¹is independently a hydrogen, C₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl 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 ³¹is independently —O—, —NR²¹—, —NR²¹—C(O)—, —C(O)—NR²¹—, —NR—S(O)₂— or —S(O)₂—NR²¹—;

R ⁴is a hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl or R²⁰—Z²⁰-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 ⁴is a radical of hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₁-C₆haloalkyl of 1-3 halo radicals, C₂-C₆haloalkenyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁-C4 alkyl, heteroaryl-C₁-C₄alkyl or R²⁰—Z²⁰—C₁-C₆alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, (C₁-C₄alkoxy)carbonylamino, (C₁-C₄alkoxy)carbonyl, cyano, halo, azido, C₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals or C₁-C₄haloalkoxy of 1-3 halo radicals;

more preferably, R ⁴is a radical of hydrogen, C₁-C₆alkyl, aryl, heteroaryl, aryl-C₁-C₄alkyl, heteroaryl-C₁-C₄alkyl or R²⁰—Z²⁰—C₂-C₄alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, acetylamino, halo, C₁-C₄alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, R is a radical of hydrogen, C ₁-C₆alkyl, aryl, heteroaryl, aryl-C₁-C₄alkyl, heteroaryl-C₁-C₄alkyl or R²⁰—Z²⁰—C₂-C₄alkyl 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 ⁴is a radical of hydrogen, methyl or ethyl radical;

wherein each R ¹⁸is 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 is independently a hydrogen, C ₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl, C₁-C₄alkylsulfonyl, (C₁-C₄alkoxy)carbonylamino, (C₁-C₄alkoxy)carbonyl, cyano, halo, azido, C₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals or C₁-C₄haloalkoxy of 1-3 halo radicals;

more preferably, each R ¹⁸is independently a hydrogen, C₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₂alkyl or heteroaryl-C₁-C₂alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, acetylamino, cyano, halo, azido, C₁-C₄alkyl, trifluoromethyl or trifluoromethoxy;

each Z ¹⁸is 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—; preferably, each Z¹⁸is independently —O—, —S—, —S(O)₂—, —CO₂—, —NR²¹—, —NR²¹—C(O)—, —C(O)—NR²¹—, —NR²¹—S(O)₂— or —S(O)₂—NR²¹;

wherein each R ¹⁹is 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 is independently a hydrogen, C ₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, (C₁-C₄alkoxy)carbonylamino, (C₁-C₄alkoxy)carbonyl, cyano, halo, azido, C₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals or C₁-C₄haloalkoxy of 1-3 halo radicals;

more preferably, each R is independently a hydrogen, C ₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, acetylamino, cyano, halo, C₁-C₄alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R is independently a hydrogen, C ₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl 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 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, trifluoromethyl or trifluoromethoxy;

each Z 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—; preferably, each Z²¹is independently —O—, —S(O)₂—, —CO₂—, —C(O)—, —NR²¹—C(O)—, —C(O)—NR²¹—, —NR²¹—S(O)₂— or —S(O)₂—NR²¹—; more preferably, each Z is independently —O—, —S(O)₂—, —O—C(O)—, —C(O)—, —NR²¹—C(O)— or —NR²¹—S(O)₂—;

wherein each R ²⁰is 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 ²⁰is independently a hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, (C₁-C₄alkoxy)carbonylamino, (C₁-C₄alkoxy)carbonyl, cyano, halo, azido, C₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals or C₁-C₄haloalkoxy of 1-3 halo radicals;

more preferably, each R ²⁰is independently a hydrogen, C₁-C₄alkyl, aryl, heteroaryl, aryl-C₁-C₂alkyl or heteroaryl-C₁-C₂alkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, acetylamino, halo, C₁-C₄alkyl, trifluoromethyl or trifluoromethoxy;

more preferably, each R ²⁰is independently a hydrogen, C₁-C₄alkyl, aryl, heteroaryl, aryl-C₁-C₂alkyl or heteroaryl-C₁-C₂alkyl 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 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—; preferably, each Z²⁰is independently —O— or —NR²¹—;

wherein each R is independently a hydrogen or alkyl radical; preferably, each R ²¹is independently a hydrogen or C₁-C₄alkyl radical; more preferably, each R²¹is independently a hydrogen or methyl radical;

R ⁵and R⁶are 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 ⁵and R⁶are each independently a hydrogen, C₁-C₄alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, C₁-C₄haloalkoxy of 1-3 halo radicals, C₁-C₄aminoalkyl, (C₁-C₄alkyl)amino-C₁-C₄alkyl, di(C₁-C₄alkyl)amino-C₁-C₄alkyl, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, C₁-C₄alkylsulfonylamino, aminosulfonyl, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, hydroxy, C₁-C₄hydroxyalkyl, thiol, C₁-C₄alkylthiol, C₁-C₄alkylsulfonyl, C₁-C₄alkylsulfonyl, C₁-C₄alkoxy, (C₁-C₄alkoxy)C₁-C₄alkyl, cyano, azido, nitro, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C₄alkyl)aminocarbonyl radical;

more preferably, R ⁵and R⁶are each independently a hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, hydroxy, C₁-C₄hydroxyalkyl, C₁-C₄alkoxy, cyano, azido, nitro, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl) aminocarbonyl or di (C₁-C₄alkyl) aminocarbonyl radical;

more preferably, R ⁵and R⁶are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁-C₂alkylamino, di(C₁-C₂alkyl)amino, hydroxy, methoxy or ethoxy radical; most preferably, R⁵and R⁶are each a hydrogen radical;

R ⁷is 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 ⁷is a hydrogen, C₁-C₄alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, C₁-C₄haloalkoxy of 1-3 halo radicals, C₁-C₄aminoalkyl, (C₁-C₄alkyl)amino-C₁-C₄alkyl, di(C₁-C₄alkyl)amino-C₁-C₄alkyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, hydroxy, C₁-C₄hydroxyalkyl, thiol, C₁-C₄alkylthiol, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkoxy, (C₁-C₄alkoxy)C₁-C₄alkyl, cyano, azido, nitro, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C₄alkyl)aminocarbonyl radical;

more preferably, R ⁷is a hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, C₁-C₄hydroxyalkyl, C₁-C₄alkoxy, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C₄alkyl)aminocarbonyl radical;

more preferably, R ⁷is a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, methoxy or ethoxy radical; most preferably, R⁷is 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-dichlorophenylcarbonylamino)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-dimethylphenylcarbonylamino)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-C₁₅), more preferably 1-8 carbon atoms (C₁-C₈), even more preferably 1-6 carbon atoms (C₁-C₆), yet more preferably 1-4 carbon atoms (C₁-C₄), still more preferably 1-3 carbon atoms (C₁-C₃), and most preferably 1-2 carbon atoms (C₁-C₂). Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, 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-C₁₅), more preferably 2-8 carbon atoms (C₂-C₈), even more preferably 2-6 carbon atoms (C₂-C₆), yet more preferably 2-4 carbon atoms (C₂-C₄), and still more preferably 2-3 carbon atoms (C₂-C₃). 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-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like.

“Alkoxycarbonyl”, alone or in combination, means a radical of the type “R—O—C(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) ₂” 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 ₆H₄═ 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-C₁₂), more preferably 5-10 carbon atoms (C₅-C₁o), even more preferably 5-7 carbon atoms (C₅-C₇), 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-C₄) 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, benzimidiazolyl, 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 “pharmacologically 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 an 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 necrosis 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, arylalkyl, 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 amino 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 nitrogen 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 mono-, 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, trifluoroacetic 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 sutiable 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. Removal 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-buty-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 hydroylsis and hydrogenolysis conditions well known to those skilled in the art.

The symbols used above have the following meanings:



—CR^xR^y— =		—C(O)— =

—NR^xR^y=		—C(NR)— =

—NR— =		—S(O)₂— =

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—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 perfomed by treatment of (3) with hydrogen gas in the presence of palladium on carbon or Raney nickel, or alternatively, by treatment with SnCl ₂in 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., R³C(O)Cl or R³C(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 (R³CO₂H) 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 SnBr₂in methanolic solvent. Subsequent acylation with an appropriate activated ester (i.e.: R³CO₂H 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)₂and K₂CO₃in DMF at 140° C. provides compounds of formula (1) where

6-Substituted-2-halo-5-nitro-pyridine analogs (6) may be prepared from 2,6-dichloro-5-nitropyridine 15 according to the methods outlined in Scheme II. Treatment with one equivalent of an appropriate nucleophile of R ⁷or a precursor thereof (such as, HO⁻, RO⁻, AcS⁻, NC⁻, RS⁻and the like) provides (6). Subsequent reaction to form (7) (treatment with R¹—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 R⁴) 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 (R⁷═CO₂H) 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 R⁷═—CN, may be reduced to the primary amine (R⁷═—CH₂NH₂) using reagents such as BH₃or 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=—CH₂NH₂may 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 ⁶and/or R⁷is 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 NaNH₂, 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 ³R⁴NH) 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 R¹—X—H in the presence of absence of base, or Cu(I) in an approriate 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 ¹R²and NHR³R⁴are 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 prescence 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. Schoenenberger, Eur. J. Med. Chem. 25, 35-44, 1990; M. Freiberger and R. B. Hasbrouck, J. Am. Chem. Soc. 82, 696-698, 1960; Dornow and Fust, Chem. Ber. 87, v984, 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, heterocyclylmercaptans, heteroarylmercaptans, alkylhalides, arylhalides, heterocyclylhalides, 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, ethers such as THF and dioxane, and acetonitrile, 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 adminstration 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 Bundgaard 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. [0171]
Preparation of 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine [0172]
Step A: 2-(4-Chloro-2-methyl-phenoxy)-5-nitropyridine [0173]
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 saturated aqueous NH[0174] ₄Cl and concentrated in vacuo. The residue was redissolved in ethyl acetate then washed 2× with saturated NaHCO₃, saturated NaCl, dried over anhydrous Na₂SO₄and concentrated in vacuo.
Step B: 2-(4-Chloro-2-methyl-phenoxy)-5-amino-pyridine [0175]
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)[0176] ⁺; C₁₂H₁₁N₂OCl requires 234.7.

EXAMPLE 2

The compounds listed in Table L 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-	249
	pyridine
	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-	251
	pyridine

EXAMPLE 3

[0178]
Preparation of 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine [0179]
Step A: 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-nitropyridine [0180]
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[0181] ₃and saturated NaCl then dried over Na₂SO₄and concentrated in vacuo.
Step B: 2-(4-Chloro-2-methyl-phenoxy)-3-methyl-5-amino-pyridine [0182]
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[0183] ₂using 1:1 ethyl acetate/hexanes as eluant. MS (m/z): 248/250 (M+H)⁺C₁₃H₁₃N₂OCl 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-	250
	pyridine

EXAMPLE 5

[0185]
Preparation of N-(2-(4-Chloro-2-methyl-phenoxy)-pyridin-5-yl)-benzamide [0186]
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[0187] ₃was added and the mixture was stirred for another hour. The organic layer was separated and washed 2× with 6% aqueous NaHCO₃, dried over Na₂SO₄and 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)⁺; C₁₉H₁₅N₂O₂Cl 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
	naphthylcarbonyl-amino)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-methyl-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-dimethylphenoxy)-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)carbonyl amino)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
	dichlorophenyl)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

[0190]

EXAMPLE 8

Preparation of 2-Amino-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-benzamide [0191]
N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-2-nitro-benzamide (301 mg, 0.7 mmol) 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)[0192] ⁺; C₁₉H₁₆N₃O₂Cl requires 353.8.

EXAMPLE 9

[0193]
Preparation of N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-2-hydroxy-benzamide [0194]
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[0195] ₄Cl. The mixture was diluted with ethyl acetate then the organics were washed with water, 2× saturated NaHCO₃, saturated NaCl, dried over Na₂SO₄and concentrated in vacuo. MS (m/z): 354/356 (M+H)⁺; C₁₉H₁₅N₂O₃Cl requires 354.8.

EXAMPLE 10

[0196]
Preparation of 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine [0197]
Step A: 2-(Cyclohexylamino)-5-nitro-pyridine [0198]
Sodium hydride (60% dispersion in mineral oil, 1.99 g, 49.8 mmol) was washed 3× 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[0199] ₄Cl and concentrated in vacuo. The residue was redissolved in ethyl acetate then washed 2× with saturated NaHCO₃, saturated NaCl, dried over anhydrous Na₂SO₄and concentrated in vacuo. The product was recovered as a brown oil.
Step B: 2-(N-Cyclohexyl-N-methylamino)-5-nitro-pyridine [0200]
Sodium hydride (60% dispersion in mineral oil, 0.38 g, 9.48 mmol) was washed 3× 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[0201] ₄Cl. The reaction mixture was diluted with ethyl acetate and extracted 5× with water (200 mL), saturated NaCl, dried over Na₂SO₄and concentrated in vacuo oil was chromatographed on SiO₂using 2:1 hexanes/ethyl acetate as eluent.
Step C: 2-(N-Cyclohexyl-N-methylamino)-5-amino-pyridine [0202]
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[0203] ₂using 1:1 ethyl acetate/hexanes as eluent. MS (m/z): 206 (M+H)⁺; C₁₂H₁₉N₃requires 205.3.

EXAMPLE 11

[0204]
Preparation of 2-(N-(2,4-dimethyl-phenyl)-N-methylamino)-5-amino-pyridine [0205]
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. [0206]

EXAMPLE 12

[0207]
Preparation of 2,6-Dichloro-N-(2-(N′-cyclohexyl-N′-methylamino)-pyridin-5-yl)-benzamide [0208]
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 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[0209] ₄Cl and stirring for an additional 5 hours. The organic layer was separated and dried over Na₂SO₄then concentrated in vacuo. The crude product was purified by chromatography on SiO₂using 1:1 ethyl acetate/hexane as eluent. MS (m/z): 378/380 (M+H)⁺; C₁₉H₂₁NOC; 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)carbonyl amino)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)carbonylamino)pyridine
	2-(2,4-dimethylphenyl)-5-((2-	349
	fluorophenyl)carbonylamino)pyridine
	2-(2,4-dimethylphenyl)-5-((2,6-	400
	dichlorophenyl)carbonylamino)pyridine

EXAMPLE 14

[0211]
Preparation of 2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine [0212]
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[0213] ₂using 30% ethyl acetate / hexanes as eluent. MS (m/z): 248/250 (M+H)⁺; C₁₃H₁₃N₂OCl requires 249.

EXAMPLE 15

[0214]
Preparation of 2 6-Dichloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide [0215]
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[0216] ₄Cl and stirring for an additional 5 hours. The organic layer was separated and dried over Na₂SO₄then concentrated in vacuo. The crude product was purified by chromatography on SiO₂using 1:1 ethyl acetate/hexane as eluent. MS (m/z): 422/424 (M+H)⁺; C₂₀H₁₅N₂O₂Cl₃requires 422.

EXAMPLE 16

[0217]
Preparation of 2-Chloro-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide [0218]
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. [0219]

EXAMPLE 17

[0220]
Preparation of 2-Methyl-N-(6-(4-chloro-2-methyl-phenoxy)-pyridin-3-yl)-N-methyl-benzamide [0221]
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. [0222]

EXAMPLE 18

[0223]
General procedure for the synthesis of 2-substituted-5-acylamino-pyridines [0224]
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. [0225]

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
R¹X	R³	(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
methylphenoxy
4-chloro-2-	3-bromophenyl	418
methylphenoxy
4-chloro-2-	3-pyridyl	340
methylphenoxy
4-chloro-2-	2-ethoxynaphth-1-yl	433
methylphenaxy
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-
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
l-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	2,41 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-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	2,6-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-l,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-trimethylphenyl	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-3-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	332
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	363
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-(methylthiopyridin-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
213-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
	chlorophenoxyl 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-(phenylthiopyrid-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
315-(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
315-(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-ethoxypheny)	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-35-	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-methyl-phenyl	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	(trifluorophenyl)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
dimethyl-phenoxy
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
dimethyl-phenoxy
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 [bi 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	benzo furoxan-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
methylphenyl thio
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-
	4-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-	2,4-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


	R¹X	R³

	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	1-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	pentafluorophenyl
	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-	4-biphenyl
	dimethylphenoxy
	4-chloro-2,5-	4-cyanophenyl
	dimethylphenoxy
	4-chloro-2,5-	3-cyanophenyl
	dimethylphenoxy
	4-chloro-2,5-	4-nitrophenyl
	dimethylphenoxy
	4-chloro-2,5-	5-nitrofuran-2-yl
	dimethylphenoxy
	4-chloro-2,5-	3-nitrophenyl
	dimethylphenoxy
	4-chloro-2,5-	4-(trifluoromethyl)phenyl
	dimethylphenoxy
	4-chloro-2,5-	2-nitrophenyl
	dimethylphenoxy
	4-chloro-2,5-	thien-2-yl
	dimethylphenoxy
	4-chloro-2,5-	3,5-difluorophenyl
	dimethylphenoxy
	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)	4-biphenyl
	phenoxy
	4-(2-(2-methyl)propyl)	4-cyanophenyl
	phenoxy
	4-(2-(2-methyl)propyl)	3-cyanophenyl
	phenoxy
	4-(2-(2-methyl)propyl)	4-nitrophenyl
	phenoxy
	4-(2-(2-methyl)propyl)	5-nitrofuran-2-yl
	phenoxy
	4-(2-(2-methyl)propyl)	3-nitrophenyl
	phenoxy
	4-(2-(2-methyl)propyl)	4-(trifluoromethyl)phenyl
	phenoxy
	4-(2-(2-methyl)propyl)	2-nitrophenyl
	phenoxy
	4-(2-(2-methyl)propyl)	thien-2-yl
	phenoxy
	4-(2-(2-methyl)propyl)	3,5-difluorophenyl
	phenoxy
	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-	4-biphenyl
	cyclohexylphenoxy
	4-chloro-2-	4-cyanophenyl
	cyclohexylphenoxy
	4-chloro-2-	3-cyanophenyl
	cyclohexylphenoxy
	4-chloro-2-	4-nitrophenyl
	cyclohexylphenoxy
	4-chloro-2-	5-nitrofuran-2-yl
	cyclohexylphenoxy
	4-chloro-2-	3-nitrophenyl
	cyclohexylphenoxy
	4-chloro-2-	4-(trifluoromethyl)phenyl
	cyclohexylphenoxy
	4-chloro-2-	2-nitrophenyl
	cyclohexylphenoxy
	4-chloro-2-	thien-2-yl
	cyclohexylphenoxy
	4-chloro-2-	3,5-difluorophenyl
	cyclohexylphenoxy
	4-chloro-3,5-	4-biphenyl
	dimethylphenoxy
	4-chloro-3,5-	4-cyanophenyl
	dimethylphenoxy
	4-chloro-3,5-	3-cyanophenyl
	dimethylphenoxy
	4-chloro-3,5-	4-nitrophenyl
	dimethylphenoxy
	4-chloro-3,5-	5-nitrofuran-2-yl
	dimethylphenoxy
	4-chloro-3,5-	3-nitrophenyl
	dimethylphenoxy
	4-chloro-3,5-	4-(trifluoromethyl)phenyl
	dimethylphenoxy
	4-chloro-3,5-	2-nitrophenyl
	dimethylphenoxy
	4-chloro-3,5-	thien-2-yl
	dimethylphenoxy
	4-chloro-3,5-	3,5-difluorophenyl
	dimethylphenoxy
	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-	4-pentylphenyl
	methylphenylthio
	4-chloro-2-	2-(4-chlorophenylthio)
	methylphenylthio	pyridin-3-yl
	4-chloro-2-	2,6-dimethylphenyl
	methylphenylthio
	4-chloro-2-	2,5-dimethoxyphenyl
	methylphenylthio
	4-chloro-2-	2,5-dichloropyridin-3-yl
	methylphenylthio
	4-chloro-2-	2-chloro-6-methoxypyridin-
	methylphenylthio	4-yl
	4-chloro-2-	2,3-dichloropyridin-5-yl
	methylphenylthio
	4-chloro-2-	1-naphthyl
	methylphenylthio
	4-chloro-2-	2,4-dimethoxyphenyl
	methylphenylthio
	4-chloro-2-	3,5-bis(trifluoromethyl)
	methylphenylthio	phenyl
	4-chloro-2-	2-(4-
	methylphenylthio	chlorophenoxy)pyridin-3-yl
	4-chloro-2-	pentafluorophenyl
	methylphenylthio
	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

[0228]
General procedure for the synthesis of 6-(substituted-amino)-N-substituted nicotinamides [0229]
Step A. General procedure for the preparation of 6-chloro-N-substituted nicotinamide: [0230]
To a suspension of 6-chloronicotinoyl chloride (1.76 g, 10.0 mmol) in dry dichloromethane (10 mL) was added the amine (R[0231] ³R⁴NH) (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: [0232]
6-Chloro-N-o-tolylnicotinamide: MS (m/z): 247/249 (M+H)[0233] ⁺; C₁₃H₁₁ClN₂O₁requires 246.5.
6-Chloro-N-(2-fluorophenyl)nicotinamide: MS (m/z): 251/253 (M+H)[0234] ⁺; C₁₂H₈Cl₁F₁N₂O₁requires 250.7.
6-Chloro-N-(2,6-dimethylphenyl)nicotinamide: MS (m/z): 261/263 (M+H)[0235] ⁺; C₁₄H₁₃Cl₁N₂O₁requires 260.7.
6-Chloro-N-(2-phenoxyphenyl)nicotinamide: MS (m/z): 325/327 (M+H)[0236] ⁺; C₁₈H₁₃ClN₂O₁requires 324.8.
6-Chloro-N-phenylnicotinamide: MS (m/z): 233/235 (M+H)[0237] ⁺; C₁₂H₈ClN₂O₁requires 232.7.
6-Chloro-N-(2,4-difluorophenyl)nicotinamide: MS (m/z): 269/271 (M+H)[0238] ⁺; C₁₂H₇Cl₁F₂N₂O₁requires 2:68.6.
6-Chloro-N-(2,6-diisopropylphenyl)nicotinamide: MS (m/z): 317/319 (M+H)[0239] ⁺; C₁₈H₂₁Cl₁N₂O₁requires 316.8.
6-Chloro-N-(4-chlorophenyl)-N-methylnicotinamide: MS (m/z): 281/283 (M+H)[0240] ⁺; C₁₃H₁₀Cl₂N₂O₁requires 281.1.
6-Chloro-N-(2,4-dimethoxyphenyl)nicotinamide: MS (m/z): 293/295 (M+H)[0241] ⁺; C₁₄H₁₃Cl₁N₂O₃requires 292.7.
6-Chloro-N-(3-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H)[0242] ⁺; C₁₃H₁₁Cl₁N₂O₂requires 262.7.
6-Chloro-N-(4-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H)[0243] ⁺; C₁₃H₁₁Cl₁N₂O₂requires 262.7.
6-Chloro-N-(2-methoxyphenyl)nicotinamide: MS (m/z): 263/265 (M+H)[0244] ⁺; C₁₃H₁₁Cl₁N₂O₂requires 262.7.
6-Chloro-N-methyl-N-phenylnicotinamide: MS (m/z): 247/249 (M+H)[0245] ⁺; C₁₃H₁₁Cl₁N₂O₁requires 246.7.
N-Benzyl-6-chloronicotinamide: MS (m/z): 247/249 (M+H)[0246] ⁺; C₁₃H₁₁Cl₁N₂O₁requires 246.7.
Step B. General procedure for the preparation of 6-(substituted-amino)-N-substituted nicotinamides [0247]
A mixture of the 6-chloro-N-substituted nicotinamide (12.5 mmol) and amine (R[0248] ¹NH₂or R¹NHCH₃) (20 mmol) in ethylene glycol (50 mL) or pyridine (alkylamines) (50 mL) was heated to 140° C. 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

		MS
R³	R¹	(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-(trifluoromethoxy)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-cyclohexyl	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
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

		MS
R³	R¹	(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
R³	R¹	(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-dimethoxyphenyl	N-methylphenyl	363
2,4-dimethoxyphenyl	4-chloro-N-methylphenyl	398
2,4-dimethoxyphenyl	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
R³	R¹	(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

	R¹X	R³

	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	cyclohexyl
	4-methoxyphenyl	indan-1-yl
	4-methoxyphenyl	2-dicyclohexyl
	2-methoxyphenyl	cycloheptyl
	2-methoxyphenyl	indan-1-yl
	2-methoxyphenyl	2-dicyclohexyl

TABLE 13

	R¹X	R³

	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 TNF-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. [0255]
Lipopolysaccharide-activated monocyte TNF production assay [0256]
Isolation of monocytes [0257]
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[0258] 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% CO₂. 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 [0259]
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. [0260]
Treatment of cells with test compounds and activation of TNF production with lipopolysaccharide [0261]
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 [0262] 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 [0263]
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[0264] ₂-free ELISA buffer supplemented to contain 20 mg/ml BSA (standard ELISA buffer: 20 mM, 150 mM NaCl, 2 mM CaCl₂, 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 μl/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_maxplate reader.
Data analysis [0265]
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. [0266]
The following compounds had an IC[0267] ₅₀of less than 15 μM:
2-cyclohexyloxy-5-(2-chlorophenylcarbonylamino)pyridine; [0268]
2-cyclohexyloxy-5-(2-methylphenylcarbonylamino)pyridine; [0269]
2-cyclohexyloxy-5-(2,6-dichlorophenylcarbonylamino) pyridine; [0270]
2-cyclohexyloxy-5-(2,6-dimethylphenylcarbonylamino) pyridine; [0271]
2-(2,4-dimethylphenoxy)-5-(2-methylphenylcarbonylamino) pyridine; [0272]
2-(2-methyl-4-fluorophenoxy)-5-(2-methylphenylcarbonyl amino)pyridine; [0273]
2-(2-methyl-4-chlorophenoxy)-5-(2-chlorophenylcarbonyl amino)pyridine; [0274]
2-(2-methyl-4-chlorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine; [0275]
2-(2-methyl-4-chlorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine; [0276]
2-(4-chlorophenoxy)-5-(2,6-dimethylphenylcarbonylamino) pyridine; [0277]
2-(2-methyl-4-fluorophenoxy)-5-(2,6-dichlorophenyl carbonylamino)pyridine; [0278]
2-(2-methyl-4-fluorophenoxy)-5-(2,6-dimethylphenyl carbonylamino)pyridine; [0279]
2-(2-methyl-4-fluorophenoxy)-5-(2-fluorophenylcarbonyl amino)pyridine; [0280]
2-(2,4-dimethylphenoxy)-5-(2,6-dimethylphenylcarbonyl amino)pyridine; [0281]
2-(l-naphthyloxy)-5-(2-methylphenylcarbonylamino) pyridine; [0282]
2-(1-naphthyloxy)-5-(2,6-dichlorophenylcarbonylamino) pyridine; [0283]
2-(2-methyl-3-pyridyloxy)-5-(2,6-dichlorophenylcarbonyl amino)pyridine; [0284]
2-(2-methyl-4-chlorophenoxy)-5-((3,5-dimethyl-4-isoxazolyl)carbonylamino)pyridine; [0285]
2-cyclohexylamino-5-(2,6-dichlorophenylcarbonylamino) pyridine; [0286]
2-cyclohexylamino-5-(2,6-dimethylphenylcarbonylamino) pyridine; [0287]
2-(2-methylcyclohexylamino)-5-(2,6-dichlorophenylcarbonylamino)pyridine; [0288]
2-(2-methylcyclohexylamino)-5-(2-methylphenylcarbonyl amino)pyridine; [0289]
2-(2-methylphenylamino)-5-(2-methylphenylcarbonyl amino)pyridine; [0290]
2-(2-methylphenylamino)-5-(2,6-dimethylphenylcarbonyl amino)pyridine; [0291]
2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl carbonylamino)pyridine; and [0292]
2-(2-methyl-4-chlorophenylamino)-5-(2-methylphenyl aminocarbonyl)pyridine. [0293]
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-A, IL-1β, IL-6, and IL-8 play a role to the full extent of the definition of TNF-α-mediated diseases described herein. [0294]
Inhibition of LPS-Induced TNF-α production in mice [0295]
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. [0296]
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. [0297]
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, New York, 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). [0298]
[0299] ¹²⁵I-Glucagon Binding Screen with CHO/hGLUR Cells
The assay is described in WO 97/16442, which is incorporated herein by reference in its entirety. [0300]
Reagents [0301]
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 (1000×): 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) [0302] ¹²⁵I-Glucagon (NEN, receptor-grade, 2200 Ci/mmol): dilute to 50,000 cpm/25 μl in assay buffer with BSA (about 50 pM final concentration in assay).
Harvesting of CHO/hGLUR Cells for Assay [0303]
1. Remove media from confluent flask then rinse once each with PBS (Ca, Mg-free) and Enzyme-free Dissociation Fluid (Specialty Media, Inc.). [0304]
2. Add 10 ml Enzyme-free Dissoc. Fluid and hold for about 4 min. at 37° C. [0305]
3. Gently tap cells free, triturate, take aliquot for counting and centrifuge remainder for 5 min. at 1000 rpm. [0306]
4. Resuspend pellet in Assay Buffer at 75000 cells per 100 μl. [0307]
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. [0308]
Assay [0309]
The determination of inhibition of glucagon binding can be carried out by measuring the reduction of I[0310] 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 ¹²⁵I- CHO/hGLUR

Vehicle Glucagon Glucagon Cells

Total —/5 μl — 25 μl 100 μl

Binding

+ 5 μl/— — 25 μl 100 μl

Compound

Nonspecific —/5 μl 1 μl 25 μl 100 μl

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. [0311]
Thus, compounds of the invention may also be shown to inhibit the binding of glucagon to glucagon receptors. [0312]
Cyclooxygenase Enzyme Activity Assay [0313]
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[0314] ₂.
COX-1 Assay [0315]
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[0316] ⁶cells/mL and plated in 96-well culture plates at a density of 5×10⁵cells/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 [0317]
For the COX-2 assay, subconfluent HOSC are trypsinized and resuspended at 3×10[0318] ⁶cells/mL in MEM-FBS containing 1 ng human IL-1b/mL, plated in 96-well tissue culture plates at a density of 3×10⁴cells 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 [0319]
After incubation with arachidonic 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[0320] ₂using a commercially available ELISA (Neogen #404110). A standard curve of PGE₂is 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[0321] ₅₀values of 10 μM or less: 2-(2,4-dimethylphenylamino)-5-(2,6-dichlorophenylcarbonyl amino)pyridine.
Raf Kinase assay [0322]
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. [0323]
MATERIALS: [0324]
Activated Raf is produced by triple transfection of Sf9 cells with baculoviruses expressing “Glu-Glu”-epitope tagged Raf,val[0325] 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. [0326]
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. [0327]
Column buffer: 20 mM Tris pH=8, 100 mM NaCl, 1 mM EDTA, 2.5 mM EGTA, 10 mM MgCl[0328] 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 aprotinin.
5× Reaction buffer: 125 mM HEPES pH=:8, 25 mM MgCl[0329] ₂, 5 mM EDTA, 5 mM Na₃VO₄, 100 μg/mL BSA.
Enzyme dilution buffer: 25 mM HEPES pH=8, 1 mM EDTA, 1 mM Na[0330] ₃VO₄, 400 μg/mL BSA.
Stop solution: 100 mM EDTA, 80 mM sodium pyrophosphate. [0331]
Filter plates: Milipore multiscreen # SE3MO78E3, Immobilon-P (PVDF). [0332]
METHODS: [0333]
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 17,000×g 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. [0334]
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 5× reaction buffer, 1 mM [0335] ³³P-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 33P 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; cachexiel; 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. [0336]
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. [0337]
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). [0338]
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. [0339]
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, II,-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. [0340]
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 arachidonic acid/prostaglandin pathway. [0341]
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. [0342]
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 dosage 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. [0343]
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 regimen 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. [0344]
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. [0345]
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. [0346]
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. [0347]
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. [0348]
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. [0349]
A suitable topical dose of active ingredient of a compound of the invention is 0.1 mg to 150 mg administered one 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. [0350]
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. [0351]
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. [0352]
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. [0353]
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. [0354]
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. [0355]
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. [0356]
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-hyroxy-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. [0357]
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. [0358]
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. [0359]
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. [0360]
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. [0361]

Claims

What is claimed is:

1. A compound of the formula

or a pharmaceutically acceptable salt thereof, wherein

X is O, S, S(O), S(O)₂or NR²;

Y is —C(O)—NR³R⁴or —NR⁴—C(O)—R³;

R¹is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R¹⁸—Z^—or R¹⁸—Z¹⁸-alkyl; provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R¹is 1-3; and provided when Y is —NR⁴—C(O)— R³and X is O or S, R¹is other than a 2-pyrimidinyl radical;

R²is a hydrogen or alkyl radical;

R³is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R¹⁹—Z¹⁹— or R¹⁹—Z¹⁹-alkyl; provided that the total number of aryl and heteroaryl radicals in R³is 1-3; and provided when Y is —C(O)—NR³R⁴, R³is 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

R⁴is a hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl or R²⁰—Z²⁰-alkyl radical;

wherein R¹⁸, R¹⁹and R²⁰are each independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical; wherein the aryl and heteroaryl radicals of R⁴, R¹⁸, R¹⁹and R²⁰are 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, Z¹⁹and Z²⁰are 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 R²¹is independently a hydrogen or alkyl radical;

R⁵and R⁶are 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

R⁷is 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, wherein

R¹is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C₁-C₆alkyl, halo, C₁-C₆haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸—Z¹⁸— or R¹⁸—Z¹⁸—C₁-C₆alkyl; provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R¹is 1-3; and provided when Y is —NR⁴—C(O)—R³and X is O or S, R¹is other than a 2-pyrimidinyl radical;

R²is a hydrogen or C₁-C₄alkyl radical;

R³is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C₁-C₆alkyl, halo, C₁-C₆haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹—Z¹⁹— or R¹⁹—Z¹⁹—C₁-C₆alkyl; provided that the total number of aryl and heteroaryl radicals in R³is 1-3; and provided when Y is —C(O)—NR³R⁴, R³is 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

R⁴is a radical of hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₁-C₆haloalkyl of 1-3 halo radicals, C₂-C₆haloalkenyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁-C₄alkyl, heteroaryl-C₁-C₄alkyl or R²⁰—Z²⁰—C₁-C₆alkyl radical; and

wherein R¹⁸, R¹⁹and R²⁰are each independently a hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl radical; wherein the aryl and heteroaryl radicals of R⁴, R¹⁸, R¹⁹and R²⁰are optionally substituted by 1-3 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-c₅alkanoylamino, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, (C₁-C₄alkoxy)carbonylamino, (C₁-C₄alkoxy)carbonyl, cyano, halo, azido, C₁-C₄alkyl, C₁-C₄haloalkyl of 1-3 halo radicals or C₁-C₄haloalkoxy of 1-3 halo radicals; and

each R²¹is independently a hydrogen or C₁-C₄alkyl radical;

R⁵and R⁶are each independently a hydrogen, C₁-C₄alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, C₁-C₄haloalkoxy of 1-3 halo radicals, C₁-C₄aminoalkyl, (C₁-C₄alkyl)amino-C₁-C₄alkyl, di(C₁-C₄alkyl)amino-C₁-C₄alkyl, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, C₁-C₄alkylsulfonylamino, aminosulfonyl, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, hydroxy, C₁-C₄hydroxyalkyl, thiol, C₁-C₄alkylthiol, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkoxy, (C₁-C₄alkoxy)C₁-C₄alkyl, cyano, azido, nitro, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C₄alkyl)aminocarbonyl radical; and

R⁷is a hydrogen, C₁-C₄alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, C₁-C₄haloalkoxy of 1-3 halo radicals, C₁-C₄aminoalkyl, (C₁-C₄alkyl)amino-C₁-C₄alkyl, di(C₁-C₄alkyl)amino-C₁-C₄alkyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, hydroxy, C₁-C₄hydroxyalkyl, thiol, C₁-C₄alkylthiol, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkoxy, (C₁-C₄alkoxy)C₁-C₄alkyl, cyano, azido, nitro, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C₄alkyl)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, wherein

X is 0 or NR²;

R¹is a cycloalkyl, aryl, heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of C₁-C₄alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁸—Z¹⁸— or R¹⁸—Z¹⁸—C₁-C₄alkyl; provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R¹is 1-2;

wherein each R¹⁸is independently a hydrogen, C₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₂alkyl or heteroaryl-C₁-C₂alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, acetylamino, cyano, halo, azido, C₁-C₄alkyl, trifluoromethyl or trifluoromethoxy; and

R²is a hydrogen or C₁-C₂alkyl radical;

R³is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C₁-C₆alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹—Z¹⁹— or R¹⁹—Z¹⁹—C₁-C₄alkyl; provided that the total number of aryl and heteroaryl radicals in R³is 1-2; and

wherein each R¹⁹is independently a hydrogen, C₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl radical; wherein the aryl and heteroaryl radicals are optionally substituted by 1-2 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, acetylamino, cyano, halo, C₁-C₄alkyl, trifluoromethyl or trifluoromethoxy; and

R⁴is a radical of hydrogen, C₁-C₆alkyl, aryl, heteroaryl, aryl-C₁-C₄alkyl, heteroaryl-C₁-C₄alkyl or R²⁰—Z²⁰—C₂-C₄alkyl radical; and

wherein R²⁰is a hydrogen, C₁-C₄alkyl, aryl, heteroaryl, aryl-C₁-C₂alkyl or heteroaryl-C₁-C₂alkyl radical; wherein the aryl and heteroaryl radicals of R⁴and R²⁰are optionally substituted by 1-2 radicals of hydroxy, C₁-C₄alkoxy, C₁-C₄alkylthiol, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, acetylamino, halo, C₁-C₄alkyl, trifluoromethyl or trifluoromethoxy; and

Z²⁰is —O— or —NR²¹—; wherein each R²¹is independently a hydrogen or methyl radical;

R⁵and R⁶are each independently a hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, hydroxy, C₁-C₄hydroxyalkyl, C₁-C₄alkoxy, cyano, azido, nitro, carboxy, (CI-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C2L alkyl)aminocarbonyl radical; and

R⁷is a hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, trifluoromethoxy, hydroxy, C₁-C₄hydroxyalkyl, C₁-C₄alkoxy, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C₄alkyl)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, wherein

R³is a radical of the formula

wherein

U is C—R¹³or N;

V and W are each independently C—R¹²or N;

R¹¹and R¹³are each independently a radical of hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R¹⁹—Z¹⁹—; and each R¹²is independently a radical of hydrogen, C₁-C₆alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, R³¹—Z³¹— or R³¹—Z³¹—C₁-C₄alkyl; provided that the combined total number of aryl and heteroaryl radicals in R¹¹, R¹²and R¹³is 0-1;

wherein each R¹⁹is independently a hydrogen, C₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl 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 Z¹⁹is 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 R³¹is independently a hydrogen, C₁-C₄alkyl, trifluoromethyl, aryl, heteroaryl, aryl-C₁-C₄alkyl or heteroaryl-C₁-C₄alkyl 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 Z³¹is independently —O—, —NR²¹—, —NR²¹—C(O)—, —C(O)—NR²¹—, —NR²¹—S(O)₂— or —S(O)₂—NR²¹—;

wherein R⁴is a radical of hydrogen, C₁-C₆alkyl, aryl, heteroaryl, aryl-C₁-C₄alkyl, heteroaryl-C₁-C₄alkyl or R²⁰—Z²⁰—C₂-C₄alkyl radical;

wherein R²⁰is a hydrogen, C₁-C₄alkyl, aryl, heteroaryl, aryl-C₁-C₂alkyl or heteroaryl-C₁-C₂alkyl radical; wherein the aryl and heteroaryl radicals of R⁴and R²⁰are 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

R⁵and R⁶are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁-C₂alkylamino, di(C₁-C₂alkyl)amino, hydroxy, methoxy or ethoxy radical; and

R⁷is 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 5 or a pharmaceutically acceptable salt thereof, wherein

R¹is a radical of the formula

wherein

R²², R²³, R²⁴, R²⁵and R²⁶are each independently a radical of hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁸—Z¹⁸— or R¹⁸—Z¹⁸—C₁-C₄alkyl; provided at least one of R²¹, R²², R²³, R²⁴and R²⁵is hydrogen; and provided that the combined total number of aryl and heteroaryl radicals in R²², R²³, R²⁴, R²⁵and R²⁶is 0-1;

wherein each Z is independently —O—, —S—, —S(O)₂—, —CO₂—, —NR²¹—, —NR²¹—C(O)—, —C(O)—NR²¹—, —NR²¹—S(O)₂— or —S(O)₂—NR²¹—; and

wherein aryl is a phenyl or biphenyl radical which is optionally benzo fused or heterocyclo fused; 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.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein

X is NR²;

R²is a hydrogen or methyl radical;

R⁴is a radical of hydrogen, methyl or ethyl radical; and

R⁵, R⁶and R⁷are each independently a hydrogen radical; and

wherein aryl is a phenyl, biphenyl or naphthyl radical; 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.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein

R¹¹and R¹³are each independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁹—O—, R¹⁹—S(O)₂—, R¹⁹—O—C(O)—, R¹⁹—C(O)—, R¹⁹—NR¹²—C(O)— or R¹⁹—NR²¹—S(O)₂—; and each R¹²is 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 R¹¹, R¹²and R¹³is 0-1; and

wherein each R¹⁹is 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, trifluoromethyl or trifluoromethoxy.

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

10. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein

X is O or NR²;

each Z¹⁸is 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 R²¹is independently a hydrogen or C₁-C₄alkyl radical;

R²is a hydrogen or C₁-C₂alkyl radical;

R³is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals of C₁-C₆alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, cyano, azido, nitro, amidino, R¹⁹—Z¹⁹— or R¹⁹—Z¹⁹—C₁-C₄alkyl; provided that the total number of aryl and heteroaryl radicals in R³is 1-2; and provided R 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

R⁴is a radical of hydrogen, C₁-C₆alkyl, aryl, heteroaryl, aryl-C1-C₄alkyl, heteroaryl-C1-C₄alkyl or R²⁰—Z²⁰—C₂-C₄alkyl radical; and

R⁵and R⁶are each independently a hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, trifluoromethoxy, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₅alkanoylamino, hydroxy, C₁-C₄hydroxyalkyl, C₁-C₄alkoxy, cyano, azido, nitro, carboxy, (C₁-C₄alkoxy)carbonyl, aminocarbonyl, (C₁-C₄alkyl)aminocarbonyl or di(C₁-C₄alkyl)aminocarbonyl radical; and

11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein

R³is a radical of the formula

wherein

U is C—R¹³or N;

V and W are each independently C—R¹²or N;

R¹¹and R¹³are each independently a radical of hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino or R¹⁹—Z¹⁹—; and each R¹²is independently a radical of hydrogen, C₁-C₆alkyl, halo, C₁-C₄haloalkyl of 1-3 halo radicals, R³¹—Z³¹— or R³¹—Z³¹—C₁-C₄alkyl; provided that the combined total number of aryl and heteroaryl radicals in R¹¹, R¹²and R¹³is 0-1; provided when U is C—R¹³and V and W are each C—R¹², R¹¹and R¹³are each other than a nitro, cyano, carboxy or alkoxycarbonyl radical;

wherein each R²¹is independently a hydrogen or methyl radical;

R⁴is a radical of hydrogen, C1-C6 alkyl, aryl, heteroaryl, aryl-C₁-C₄alkyl, heteroaryl-C₁-C₄alkyl or R²⁰—Z²⁰—C₂-C₄alkyl radical; and

wherein R° is a hydrogen, C1-C₄alkyl, aryl, heteroaryl, aryl-C₁-C₂alkyl or heteroaryl-C₁-C₂alkyl radical; wherein the aryl and heteroaryl radicals of R⁴and R²⁰are 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

R⁵and R⁶are each independently a hydrogen, methyl, ethyl, halo, trifluoromethyl, trifluoromethoxy, amino, C1-C₂alkylamino, di(C₁-C₂alkyl)amino, hydroxy, methoxy or ethoxy radical; and

12. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein

R¹is a radical of the formula

wherein

R²², R^{23 , R} ²⁴, R²⁵and R²⁶are each independently a radical of hydrogen, C₁-C₄alkyl, halo, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁸—Z¹⁸— or R¹⁸—Z¹⁸—C₁-C₄alkyl; provided at least one of R²¹, R²²,R²³, R²⁴and R²⁵is hydrogen; and provided that the combined total number of aryl and heteroaryl radicals in R²², R²³, R²⁴, R²⁵and R²⁶is 0-1;

each Z¹⁸is independently —O—, —S—, —S(O)₂—, —CO₂—, —NR²¹—, —NR²¹—C(O)—, —C(O)—NR²¹—, —NR²¹—S(O)₂— or —S(O)₂—NR²¹—; and

13. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein

X is NR²;

R²is a hydrogen or methyl radical;

R⁴is a radical of hydrogen, methyl or ethyl radical; and

R⁵, R⁶and R⁷are each independently EL hydrogen radical; and

14. The compound of claim 13 or a pharmaceutically acceptable salt thereof, wherein

R¹¹and R¹³are each independently a radical of hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, cyano, azido, nitro, amidino, R¹⁹—O—, R¹⁹—S(O)₂—, R¹⁹—O—C(O)—, R¹⁹—C(O)—, R¹⁹—NR²¹—C(O)— or R¹⁹—NR²¹—S(O)₂—; provided when U is C—R¹³and V and W are each C—R¹², R¹¹and R¹³are each other than a nitro, cyano, carboxy or alkoxycarbonyl radical; and provided that the combined total number of aryl and heteroaryl radicals in R¹¹and R¹³is 0-1;

each R¹²is 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; and

15. The compound of claim 1 which is:

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-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-dichlorophenylcarbonylamino)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; or 2-(2-methyl-4-chlorophenylamino)-5-(2:-methylphenyl aminocarbonyl)pyridine.

16. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

17. A method for prophylaxis or treatment of inflammation comprising administering an effective amount of a compound of claim 1.

18. A method for prophylaxis or treatment of inflammation comprising administering an effective amount of a composition of claim 16.

19. A method of treating cancer which comprises administering an effective amount of a compound of claim 1.

20. A method of treating cancer which comprises administering an effective amount of a composition of claim 16.

21. A method for prophylaxis or treatment of rheumatoid arthritis, Pagets disease, osteophorosis, multiple myeloma, uveititis, acute or 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 diabetes, type II diabetes, 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, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount of a compound of claim 1.

22. A method for prophylaxis or treatment of rheumatoid arthritis, Pagets disease, osteophorosis, multiple myeloma, uveititis, acute or 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, cachexial, Reiter's syndrome, type I diabetes, 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, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount of a compound of claim 16.

23. A method for prophylaxis or treatment of pain comprising administering an effective amount of a compound of claim 1.

24. A method for prophylaxis or treatment of pain comprising administering an effective amount of a composition of claim 16.