Amide Compounds, Compositions And Uses Thereof

Abstract

Compounds are provided according to formula 1: where A, B, W, X′, L, R 1 , R 3 , R 4b , and m′ are as defined herein. Provided compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, cognitive disorders, anxiety, depression, and others.

1 . A compound having a formula 1: 
       
         
           
           
               
               
           
         
         wherein
 each of A, B, and W are independently selected from CR 4 ; 
 X′ is CR 4a ; 
 L is —C(R 2a R 2b )—; 
 R 1  is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, hydroxy C 1 -C 4  alkyl, C 3 -C 7  cycloalkyl-C 1 -C 4  alkyl, or 4-7 membered heterocycloalkyl-C 1 -C 4  alkyl; 
 each of R 2a  and R 2b  is independently selected from hydrogen, C 1 -C 4  alkyl, or hydroxy C 1 -C 4  alkyl; 
 R 3  is substituted or unsubstituted C 1 -C 6  alkyl; CH(OH)R 3a , OR 3a , CN, COR 3a , COOR 3a , SOR 3a , SO 2 R 3a , CONR 3a R 3b , SONR 3a R 3b , or SO 2 NR 3a R 3b ; 
 R 3a  is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
 R 3b  is H, substituted or unsubstituted C 1 -C 6  alkyl; or R 3a  and R 3b  join together to form a cycloheteroalkyl ring of 3-7 atoms; 
 each R 4  is independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, substituted or unsubstituted amino, substituted or unsubstituted arylalkyl, sulfo, substituted sulfo, substituted sulfonyl, substituted sulfinyl, substituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, azido, substituted or unsubstituted carbamoyl, carboxyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted dialkylamino, halo, nitro, and thiol; 
 each R 4a , and R 4b  is independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkoxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, sulfo, substituted sulfo, substituted sulfonyl, substituted sulfinyl, substituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, azido, substituted or unsubstituted carbamoyl, carboxyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, halo, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol; 
 
         and subscript m′ is selected from 0-4; 
         provided that 
         i) when R 3  is CO 2 Me, SO 2 Ph, or OR 3a ; then R 1  is other than unsubstituted phenyl; 
         ii) when R 3  is SO 2 -(4-methylpiperazin-1-yl) or is SO 2 -(thiomorpholin-1-yl); and X′ is CH; then R 4b  is other than H; 
         iii) when R 3  is Me, or methyl substituted with alkoxy; then R 1  is other than substituted phenyl; 
         iv) when R 3  is CO 2 H; then R 4b  is Cl, F, Br, Me, Et, OMe, or CF 3 ; 
         v) when X′ is CR 4a ; R 3  is CONR 3a R 3b ; and R 3a  is H; then R 3b  is other than substituted n-pentyl, substituted pentynyl, substituted benzyl, substituted phenethyl, substituted thiophenylethyl, or substituted thiazolylethyl; and 
         vi) when R 1  is 5-6 membered heterocycloalkylmethyl, and R 3  is CO 2 Me or n-Pr; then R 4b  is other than Cl or 4-F; 
         or a pharmaceutically acceptable salt, N-oxide, solvate, prodrug, stereoisomer, tautomer or isotopic variant thereof. 
       
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . A compound according to  claim 1 , wherein the compound is according to formula 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, or 2n: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein 
         X′, R 1 , R 3a , R 3b , R 4a ; R 4b , and m′ are as in  claim 1 ; R 2a  is H, Me, CH 2 OH, or CH 2 CH 2 OH; and Het is substituted or unsubstituted heterocycloalkyl; or a pharmaceutically acceptable salt, solvate, N-oxide, prodrug, stereoisomer, tautomer or isotopic variant thereof. 
       
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . A compound according to  claim 1 , wherein the compound is according to formula 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m, or 3n: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein 
         X′, R 1 , R 3a , R 3b , R 4a ; and R 4b , are as in  claim 1 ; 
         R 2a  is H, Me, CH 2 OH, or CH 2 CH 2 OH; and Het is substituted or unsubstituted heterocycloalkyl; or a pharmaceutically acceptable salt, solvate, N-oxide, prodrug, stereoisomer, tautomer or isotopic variant thereof. 
       
     
     
         10 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein the compound is according to formulae 2b, 2c, 2h, 2i, 3b, 3c, 3h, or 3i; and R 3a  is H. 
     
     
         11 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein R 3a  is substituted or unsubstituted alkyl. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein R 3a  is pyridylmethyl, piperidinylmethyl, piperazinylmethyl, pyrrolidinylmethyl, morpholinylmethyl, pyridylethyl, piperidinylethyl, piperazinylethyl, pyrrolidinylethyl, or morpholinylethyl. 
     
     
         17 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein R 3a  is cyclopropyl, cyclopentyl, cyclopropylmethyl, or cyclopentylmethyl. 
     
     
         18 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein R 3a  is substituted or unsubstituted heteroaryl. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein R 3a  is pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, thiadiazolyl, unsubstituted or substituted with alkyl or haloalkyl. 
     
     
         22 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein R 3a  is selected from substituted or unsubstituted phenyl, pyridyl, pyrazinyl, pyrimidinyl, quinolinyl, isoquinolinyl, methylenedioxyphenyl, imidazopyridyl, benzoxazolyl, benzothiazolyl, and indolyl. 
     
     
         23 . A compound according to any one of  claims 1 ,  5 , and  9 , wherein R 3a  is 
       
         
           
           
               
               
           
         
         and wherein subscript n1 is selected from 1-5 and each R 5a  is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkoxy, aryloxy, alkoxycarbonyl, substituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, arylalkyloxy, substituted arylalkyloxy, amino, aryl, substituted aryl, arylalkyl, sulfo, substituted sulfo, substituted sulfinyl, substituted sulfonyl, substituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, azido, substituted or unsubstituted carbamoyl, carboxyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, halo, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol. 
       
     
     
         24 . A compound according to either of  claims 5 , or  9 , wherein R 3b  is H or alkyl. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . A compound according to either of  claim 5 , or  9 , wherein Het is azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholin-1-yl, piperazin-1-yl, and azepin-1-yl, unsubstituted or substituted with one or more groups selected from alkyl, alkoxy, dialkylamino, halo, haloalkyl, hydroxy, or hydroxyalkyl. 
     
     
         28 . (canceled) 
     
     
         29 . A compound according to  claim 1 , wherein the compound is according to formula 4, 5, 6, 7, 8, or 9: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein 
         X′, R 1 , R 4b ; and m′ are as in  claim 1 ; R 5c  is R 5a ; the subscript n3 is 1, 2, or 3; and R 5a  is selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkoxy, aryloxy, alkoxycarbonyl, substituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, arylalkyloxy, substituted arylalkyloxy, amino, aryl, substituted aryl, arylalkyl, sulfo, substituted sulfo, substituted sulfinyl, substituted sulfonyl, substituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, azido, substituted or unsubstituted carbamoyl, carboxyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, halo, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol; 
         R 2a  is H, Me, CH 2 OH, or CH 2 CH 2 OH; R 2b  is H; and Q is —O—, or —C(OH)H—; 
         or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, tautomer or isotopic variant thereof. 
       
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . A compound according to  claim 1 , wherein the compound is according to formula 10, 11, 12, 13, 14, or 15: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein 
         X′, R 1 , R 4a , and R 4b  are as in  claim 1 ; R 5a  is H, Cl, F, Me, OMe, or CF 3 ; and the subscript n3 is 1, or 2; 
         R 2a  is H, Me, CH 2 OH, or CH 2 CH 2 OH; R 2b  is H; and Q is —O—, or —C(OH)H—; 
         or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, tautomer or isotopic variant thereof. 
       
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . A compound according to any one of  claims 1 ,  5 ,  9 , and  32 , wherein X′ is CR 4a  or N; and R 4a  is H, C 1 -C 4  alkyl, halo C 1 -C 4  alkyl, CN, NO 2 , or halo. 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . A compound according to any one of  claims 1 ,  5 ,  9 , and  32 , wherein R 4b  is H, C 1 -C 4  alkyl, halo C 1 -C 4  alkyl or halo. 
     
     
         40 . (canceled) 
     
     
         41 . A compound according to any one of  claims 1 ,  5 ,  9 , and  32 , wherein R 1  is substituted or unsubstituted aryl or heteroaryl. 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . A compound according to any one of  claims 1 ,  5 ,  9 , and  32 , wherein R 1  is selected from substituted or unsubstituted phenyl, pyridyl, pyrazinyl, thiazolyl, pyrimidinyl, quinolinyl, isoquinolinyl, methylenedioxyphenyl, imidazopyridyl, benzoxazolyl, benzothiazolyl, and indolyl. 
     
     
         46 . A compound according to any one of  claims 1 ,  5 ,  9 , and  32 , wherein R 1  is 
       
         
           
           
               
               
           
         
         and wherein subscript n2 is selected from 1-5 and each R 5b  is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkoxy, aryloxy, alkoxycarbonyl, substituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, arylalkyloxy, substituted arylalkyloxy, amino, aryl, substituted aryl, arylalkyl, sulfo, substituted sulfo, substituted sulfinyl, substituted sulfonyl, substituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, azido, substituted or unsubstituted carbamoyl, carboxyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, halo, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol. 
       
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . A compound according to any one of  claims 1 ,  5 ,  9 , and  32 , wherein R 1  is 
       
         
           
           
               
               
           
         
         and wherein R 5b  is selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkoxy, aryloxy, alkoxycarbonyl, substituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, arylalkyloxy, substituted arylalkyloxy, amino, aryl, substituted aryl, arylalkyl, sulfo, substituted sulfo, substituted sulfinyl, substituted sulfonyl, substituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, azido, substituted or unsubstituted carbamoyl, carboxyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, halo, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol. 
       
     
     
         50 . A compound according to  claim 49 , wherein each R 5b  is independently selected from H, alkyl, halo, cyano, alkoxy, and haloalkyl. 
     
     
         51 . (canceled) 
     
     
         52 . (canceled) 
     
     
         53 . (canceled) 
     
     
         54 . (canceled) 
     
     
         55 . (canceled) 
     
     
         56 . (canceled) 
     
     
         57 . A compound according to  claim 1 , wherein R 2a  is methyl, hydroxymethyl or hydroxyethyl. 
     
     
         58 . (canceled) 
     
     
         59 . (canceled) 
     
     
         60 . A compound according to  claim 1 , selected from
 4′-Methyl-5-(propane-1-sulfonyl)-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;   2,4′-Dimethyl-5-(pyrrolidine-1-sulfonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   2′-Cyano-4′-methyl-5-(pyrrolidine-1-sulfonyl)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(pyrrolidine-1-sulfonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(2-methyl-propane-1-sulfonyl)-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;   5-Cyclopentanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;   4′-Methyl-5-(propane-2-sulfonyl)-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;   3-Methanesulfonyl-5-(5-methyl-pyridin-2-yl)-N-(2-methyl-pyrimidin-5-ylmethyl)-benzamide;   3-(4-Hydroxy-pyrrolidin-3-yloxy)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-benzamide;   5-(2-Dimethylamino-1-hydroxy-ethyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(4-methyl-3-oxo-piperazine-1-carbonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(2-methyl-aziridine-1-carbonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid ((S)-1-methyl-2-morpholin-4-yl-ethyl)-amide;   5-[1-Hydroxy-2-(4-methyl-piperazin-1-yl)-ethyl]-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide; and   5-{1-Hydroxy-2-[(2-hydroxy-ethyl)-methyl-amino]-ethyl}-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, tautomer or isotopic variant thereof.   
     
     
         61 . A compound according to  claim 1 , selected from
 4′-Methyl-biphenyl-3,5-dicarboxylic acid 5-[(6-chloro-pyridin-3-ylmethyl)-amide]3-(isobutyl-methyl-amide);   4′-Methyl-biphenyl-3,5-dicarboxylic acid 3-(isobutyl-methyl-amide) 5-[(2-methyl-pyrimidin-5-ylmethyl)-amide];   4′-Methyl-biphenyl-3,5-dicarboxylic acid 3-(isobutyl-methyl-amide) 5-{[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide};   4′-Methyl-5-[(2-methyl-pyrimidin-5-ylmethyl)-carbamoyl]-biphenyl-3-carboxylic acid ethyl ester;   5-(3,3-Difluoro-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(piperidine-1-carbonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-(Azepane-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [1-(4-chloro-3-methanesulfonyl-phenyl)-ethyl]-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-(Azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-(3-Methoxy-pyrrolidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(2-trifluoromethyl-pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-(3,3-Difluoro-pyrrolidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid 3-methanesulfonyl-4-methyl-benzylamide;   2′-Cyano-4′-methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(propane-1-sulfonyl)-biphenyl-3-carboxylic acid 3-methanesulfonyl-4-methyl-benzylamide;   4′-Methyl-5-(propane-1-sulfonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (2-methoxy-pyrimidin-5-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (imidazo[1,2-a]pyridin-7-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Methyl-5-(propane-1-sulfonyl)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Methyl-5-(propane-1-sulfonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(propane-1-sulfonyl)-biphenyl-3-carboxylic acid (imidazo[1,2-a]pyridin-7-ylmethyl)-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   2′-Cyano-4′-methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   2′-Cyano-5-(3-hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   2′-Cyano-5-(3-hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-trifluoromethyl-pyridin-3-ylmethyl)-amide;   2′-Cyano-4′-methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (6-chloro-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid 3-methanesulfonyl-4-methyl-benzylamide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (1,1-dioxo-2,3-dihydro-1H-1$1%6&-benzo[b]thiophen-6-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (3-chloro-5-trifluoromethyl-pyridin-2-ylmethyl)-amide;   5-(Azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-(Azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methoxy-pyrimidin-5-yl)-ethyl]-amide;   5-(Azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (3,5-dichloro-pyridin-2-ylmethyl)-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(S)-1-(6-difluoromethyl-pyridin-3-yl)-2-hydroxy-ethyl]-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (benzooxazol-5-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (6-chloro-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(S)-2-hydroxy-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amide;   5-((R)-3-Hydroxy-pyrrolidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(S)-2-hydroxy-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid 4-chloro-3-[1,2,4]triazol-4-yl-benzylamide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   4′-Methyl-5-(pyrrolidine-1-sulfonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   3-(5-Methyl-pyridin-2-yl)-N-(6-methyl-pyridin-3-ylmethyl)-5-(pyrrolidine-1-sulfonyl)-benzamide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(R)-1-(5-chloro-1-methyl-1H-pyrazol-4-yl)-ethyl]-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   3-(5-Methyl-pyridin-2-yl)-N-[1-(6-methyl-pyridin-3-yl)-ethyl]-5-(pyrrolidine-1-carbonyl)-benzamide;   3-(5-Methyl-pyridin-2-yl)-N-(6-methyl-pyridin-3-ylmethyl)-5-(pyrrolidine-1-carbonyl)-benzamide;   3-(5-Methyl-pyridin-2-yl)-5-(pyrrolidine-1-carbonyl)-N-(6-trifluoromethyl-pyridin-3-ylmethyl)-benzamide;   5-(Hexahydro-pyrrolo[1,2-a]pyrazine-2-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (3-chloro-5-trifluoromethyl-pyridin-2-ylmethyl)-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-trifluoromethyl-pyridin-3-ylmethyl)-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-chloro-pyridin-3-ylmethyl)-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   5-(3-Hydroxy-azetidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (3,5-dichloro-pyridin-2-ylmethyl)-amide;   3-(5-Methyl-pyridin-2-yl)-5-(pyrrolidine-1-carbonyl)-N—[(R)-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-benzamide;   3-((R)-3-Hydroxy-pyrrolidine-1-carbonyl)-5-(5-methyl-pyridin-2-yl)-N-(6-trifluoromethyl-pyridin-3-ylmethyl)-benzamide;   3-((R)-3-Hydroxy-pyrrolidine-1-carbonyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-benzamide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (6-methoxy-pyridin-3-ylmethyl)-amide;   5-((R)-3-Hydroxy-pyrrolidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-((R)-3-Hydroxy-pyrrolidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amide;   4′-Methyl-biphenyl-3,5-dicarboxylic acid 3-(methyl-pyridin-4-ylmethyl-amide) 5-[(6-methyl-pyridin-3-ylmethyl)-amide];   4′-Methyl-biphenyl-3,5-dicarboxylic acid 5-[(6-methyl-pyridin-3-ylmethyl)-amide]3-[methyl-(2,2,2-trifluoro-ethyl)-amide];   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-5-(pyrrolidine-1-carbonyl)-benzamide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-5-(pyrrolidine-1-carbonyl)-benzamide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-((R)-3-Hydroxy-pyrrolidine-1-carbonyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   3-((R)-3-Hydroxy-pyrrolidine-1-carbonyl)-5-(5-methyl-pyridin-2-yl)-N-(6-methyl-pyridin-3-ylmethyl)-benzamide;   4′-Methyl-5-(2-methyl-propane-1-sulfonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(2-methyl-propane-1-sulfonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-(2,5-Dimethyl-pyrrolidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   5-(Hexahydro-pyrrolo[1,2-a]pyrazine-2-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-(Hexahydro-pyrrolo[1,2-a]pyrazine-2-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(7-Aza-bicyclo[2.2.1]heptane-7-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(2-methyl-propane-1-sulfonyl)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-((2R,5R)-2,5-Dimethyl-pyrrolidine-1-carbonyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(propane-2-sulfonyl)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   4′-Methyl-5-(propane-2-sulfonyl)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Methyl-5-(propane-2-sulfonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Bromo-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(propane-2-sulfonyl)-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-3-hydroxy-1-(6-methyl-pyridin-3-yl)-propyl]-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(S)-2-hydroxy-1-(6-methoxy-pyridin-3-yl)-ethyl]-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(S)-1-(6-difluoromethyl-pyridin-3-yl)-2-hydroxy-ethyl]-amide;   5-Ethanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-Ethanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-Ethanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   5-Ethanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   4′-Bromo-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Bromo-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-Cyclopentanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-Cyclopentanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(S)-2-hydroxy-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-3-hydroxy-1-(6-methoxy-pyridin-3-yl)-propyl]-amide;   4′-Methyl-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (6-methyl-1-oxy-pyridin-3-ylmethyl)-amide;   4′-Methyl-5-(pyrimidin-2-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   4′-Methyl-5-(thiazol-2-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Methyl-5-(thiazol-2-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(Hydroxy-pyridin-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   5-(Hydroxy-pyridin-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(2-Methoxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   5-(2-Methoxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(2-Methoxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-5-(2-methoxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-(2-methoxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(thiazol-2-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(thiazol-2-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-1-oxy-pyridin-3-ylmethyl)-amide;   5-Methanesulfonyl-4′-methyl-biphenyl-3-carboxylic acid [(S)-2-hydroxy-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(pyridin-2-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-5-(thiazol-2-yloxy)-benzamide;   5-(Hydroxy-pyridin-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid (2-methyl-pyrimidin-5-ylmethyl)-amide;   5-(Hydroxy-pyridin-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-5-(thiazol-2-yloxy)-benzamide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-5-(pyridin-2-yloxy)-benzamide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-5-(pyridin-2-yloxy)-benzamide;   3-(Hydroxy-phenyl-methyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   3-(Hydroxy-phenyl-methyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-benzamide;   2′-Cyano-5-(hydroxy-phenyl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-5-(hydroxy-phenyl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(Hydroxy-thiazol-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(Hydroxy-thiazol-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-5-(hydroxy-pyridin-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-(hydroxy-pyridin-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   3-(Hydroxy-pyridin-2-yl-methyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-benzamide;   3-(Hydroxy-pyridin-2-yl-methyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   5-(1,2-Dihydroxy-ethyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-hydroxymethyl-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(Hydroxy-thiazol-2-yl-methyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   3-(Hydroxy-thiazol-2-yl-methyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-benzamide;   2′-Cyano-5-(hydroxy-thiazol-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-5-(hydroxy-thiazol-2-yl-methyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(2,2,2-trifluoro-1-hydroxy-ethyl)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(2,2,2-trifluoro-1-hydroxy-ethyl)-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   2′-Cyano-5-(1,2-dihydroxy-ethyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(2-Methoxy-1-methyl-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(2-Methoxy-1-methyl-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   5-(2-Hydroxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-(2-hydroxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   4′-Methyl-5-(tetrahydro-furan-3-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   4′-Methyl-5-(tetrahydro-furan-2-ylmethoxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-(1-hydroxy-ethyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(tetrahydro-furan-2-ylmethoxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(tetrahydro-furan-3-ylmethoxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(tetrahydro-furan-3-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-(2-methoxy-1-methyl-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-([1,4]dioxan-2-ylmethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(2,3-Dihydroxy-propoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(1-Hydroxy-ethyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(1-Hydroxymethyl-2-methoxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(2-Methoxy-1-methyl-ethoxy)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   5-[Hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(1-Hydroxy-ethyl)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-5-(tetrahydro-furan-3-yloxy)-benzamide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-5-(tetrahydro-furan-3-ylmethoxy)-benzamide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-5-(tetrahydro-furan-2-ylmethoxy)-benzamide;   5-(4-Hydroxy-tetrahydro-furan-3-yloxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-(4-hydroxy-tetrahydro-furan-3-yloxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(2-Hydroxy-1-methyl-ethoxy)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   5-(2-Hydroxy-1-methyl-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(2-Hydroxy-1-methoxymethyl-ethoxy)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   2′-Cyano-4′-methyl-5-(2,2,2-trifluoro-1-hydroxy-ethyl)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-[Hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-4′-methyl-5-(tetrahydro-furan-3-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   4′-Methyl-5-(tetrahydro-furan-3-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-(4-Hydroxy-tetrahydro-furan-3-yloxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   2′-Cyano-5-(4-hydroxy-tetrahydro-furan-3-yloxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;   5-(1-Hydroxy-2-morpholin-4-yl-ethyl)-4′-methyl-biphenyl-3-carboxylic acid (6-methyl-pyridin-3-ylmethyl)-amide;   3-(5-Hydroxymethyl-thiazol-2-yloxy)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   2′-Cyano-4′-methyl-5-(4-methyl-thiazol-2-yloxy)-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   3-(5-Methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-5-(4-methyl-thiazol-2-yloxy)-benzamide;   3-(Benzothiazol-2-yloxy)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   2′-Cyano-5-(2-hydroxy-1-methyl-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   2′-Cyano-5-(1-hydroxymethyl-2-methoxy-ethoxy)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(1-Hydroxy-propyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide;   5-(1,2-Dimethoxy-ethyl)-4′-methyl-biphenyl-3-carboxylic acid [(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-amide; and   3-(4-Chloro-thiazol-2-yloxy)-5-(5-methyl-pyridin-2-yl)-N—[(R)-1-(6-methyl-pyridin-3-yl)-ethyl]-benzamide;   or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, tautomer or isotopic variant thereof.   
     
     
         62 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of  claim 1 . 
     
     
         63 . The pharmaceutical composition of  claim 62 , wherein the carrier is suitable for parenteral, oral, or topical administration. 
     
     
         64 . (canceled) 
     
     
         65 . (canceled) 
     
     
         66 . (canceled) 
     
     
         67 . A method for preventing or treating in a mammal in need thereof a disease or condition which comprises administering to the mammal an effective disease-treating or condition-treating amount of a compound according to  claim 1 , or a pharmaceutical composition according to any one of  claims 62 - 63 , wherein the disease or condition is selected from: pain including acute, inflammatory and neuropathic pain, chronic pain, dental pain and headache including migraine, cluster headache and tension headache, Parkinson's disease, Alzheimer's disease and multiple sclerosis; diseases and disorders which are mediated by or result in neuroinflammation, encephalitis; centrally-mediated neuropsychiatric diseases and disorders, depression mania, bipolar disease, anxiety, schizophrenia, eating disorders, sleep disorders and cognition disorders; neurological and neurodegenerative diseases and disorders; epilepsy and seizure disorders; prostate, bladder and bowel dysfunction, urinary incontinence, urinary hesitancy, rectal hypersensitivity, fecal incontinence, benign prostatic hypertrophy and inflammatory bowel disease; respiratory and airway disease and disorders, allergic rhinitis, asthma and reactive airway disease and chronic obstructive pulmonary disease; diseases and disorders which are mediated by or result in inflammation, arthritis, rheumatoid arthritis and osteoarthritis, myocardial infarction, autoimmune diseases and disorders, itch/pruritus, psoriasis; obesity; lipid disorders; cancer; and renal disorders. 
     
     
         68 . (canceled) 
     
     
         69 . (canceled) 
     
     
         70 . (canceled) 
     
     
         71 . (canceled) 
     
     
         72 . (canceled) 
     
     
         73 . (canceled) 
     
     
         74 . (canceled) 
     
     
         75 . (canceled) 
     
     
         76 . (canceled) 
     
     
         77 . (canceled)