Preparation and use of aryl alkyl acid derivatives for the treatment of obesity

Abstract

This invention relates to certain aryl alkyl acid compounds, compositions, and methods for treating or preventing obesity and related diseases.

1 . A compound of Formula (I) 
     
       
         
         
             
             
         
       
       wherein 
       Q is O, S, or NR 5 ; 
       A is a linker selected from 
     
     
       
         
         
             
             
         
       
       
         wherein p is 1 or 2 and 
       
     
     
       
         
         
             
             
         
       
       
         wherein m is 0 and n is 1, 2, 3, or 4, or 
         m is 1 and n is 1, 2, or 3, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 1  and R 2  are independently selected from hydrogen, halo, (C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxy; 
       R 3  is selected from
 hydrogen, 
 (C 1 -C 6 )alkyl optionally substituted by hydroxy, and 
 phenyl optionally substituted with (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or halo; 
 
       R 4  is selected from hydrogen, nitro, and (C 1 -C 6 )alkyl; or 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl, and 
 
       when two of said benzene ring substituents are (C 1 -C 6 )alkyl and are attached to adjacent carbon atoms of the benzene ring, they may be joined together to form a 5-7-membered carbocyclic ring; 
       R 5  is hydrogen or (C 1 -C 6 )alkyl; 
       R 6  is hydrogen; 
       R 7  is hydrogen or
 (C 1 -C 6 )alkyl optionally substituted with
 (C 1 -C 6 )alkoxy, 
 bis[(C 1 -C 3 )alkyl]amino or 
 phenyl optionally substituted with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or 
 cyano; or 
 
 
       R 6  and R 7  are both (C 1 -C 6 )alkyl; or 
       R 6  and R 7  may form, together with the carbon atom to which they are attached, a 3- to 5-membered carbocyclic ring, or
 a 6-membered ring represented by 
 
     
     
       
         
         
             
             
         
       
       
         
           wherein W is CH 2 , C(CH 3 ) 2 , O, NR 9 , S, or SO 2 ; 
         
       
       R 8  is (C 1 -C 6 )alkyl; and 
       R 9  is hydrogen or (C 1 -C 6 )alkyl; 
       or the pharmaceutically acceptable salts and esters thereof. 
     
   
   
       2 . The compound of  claim 1 , wherein
 Q is NR 5 ;   A is   
     
       
         
         
             
             
         
       
       
         wherein p is 1 or 2, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl; and 
 
       R 1 , R 2 , R 5 , R 6 , R 7 , R 8 , R 9 , and W are as defined in  claim 1 . 
     
   
   
       3 . The compound of  claim 1 , wherein
 Q is NR 5 ;   A is   
     
       
         
         
             
             
         
       
       
         wherein m is 0 and n is 1, 2, 3, or 4, or 
         m is 1 and n is 1, 2, or 3, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl; and 
 
       R 1 , R 2 , R 5 , and R 8  are as defined in  claim 1 . 
     
   
   
       4 . The compound of  claim 1 , wherein
 Q is O;   A is   
     
       
         
         
             
             
         
       
       
         wherein p is 1 or 2, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl; and 
 
       R 1 , R 2 , R 6 , R 7 , R 8 , R 9 , and W are as defined in  claim 1 . 
     
   
   
       5 . The compound of  claim 1 , wherein
 Q is O;   A is   
     
       
         
         
             
             
         
       
       
         wherein m is 0 and n is 1, 2, 3, or 4, or 
         m is 1 and n is 1, 2, or 3, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl; and 
 
       R 1 , R 2 , and R 8  are as defined in  claim 1 . 
     
   
   
       6 . The compound of  claim 1 , wherein
 Q is S;   A is   
     
       
         
         
             
             
         
       
       
         wherein p is 1 or 2, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl; and 
 
       R 1 , R 2 , R 6 , R 7 , R 8 , R 9 , and W are as defined in  claim 1 . 
     
   
   
       7 . The compound of  claim 1 , wherein
 Q is S;   A is   
     
       
         
         
             
             
         
       
       
         wherein m is 0 and n is 1, 2, 3, or 4, or 
         m is 1 and n is 1, 2, or 3, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl; and 
 
       R 1 , R 2 , and R 8  are as defined in  claim 1 . 
     
   
   
       8 . The compound of  claim 1  selected from the group consisting of: 
     4-[4′-(1H-benzimidazol-2-ylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid; 
     4-{4′-[(5-methoxy-1H-benzimidazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     trans-2-{[4′-(1H-benzimidazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5-methoxy-1H-benzimidazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-[(4′-{[5-(trifluoromethyl)-1H-benzimidazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-{[4′-(1H-benzimidazol-2-ylamino)-3′-fluoro-1,1′-biphenyl-4-yl]carbonyl}-cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(5-methoxy-1H-benzimidazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; and 
     trans-(1R,2R)-2-[(3′-fluoro-4′-{[5-(trifluoromethyl)-1H-benzimidazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid. 
   
   
       9 . The compound of  claim 1  selected from the group consisting of: 
     4-[4′-(1,3-benzoxazol-2-ylamino)-1,1′-biphenyl-4-yl]-4-oxo-2-(2-phenylethyl)butanoic acid; 
     2,2-dimethyl-4-{4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid; 
     4-{4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     4-{4′-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     2,2-dimethyl-4-{4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid; 
     2,2-dimethyl-4-{4′-[(4-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid; 
     2,2-dimethyl-4-oxo-4-[4′-(5,6,7,8-tetrahydronaphtho[2,3-d][1,3]oxazol-2-ylamino)-1,1′-biphenyl-4-yl]butanoic acid; 
     4-{4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     4-{4′-[(5-isopropyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     2,2-dimethyl-4-oxo-4-{4′-[(5-propyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}butanoic acid; 
     trans-2-({4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5,6-dimethyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-{[4′-(1,3-benzoxazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-[(4′-{[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1S,2S)-2-({4′-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid; 
     trans-2-({4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid; 
     4-{4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl)butanoic acid; 
     trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-chloro-1,3-benzoxazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; and 
     trans-(1R,2R)-2-[(3′-fluoro-4′-{[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid. 
   
   
       10 . The compound of  claim 1  selected from the group consisting of: 
     4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid; 
     4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     4-{4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     2,2-dimethyl-4-oxo-4-[4′-(1,3-thiazol-2-ylamino)-1,1′-biphenyl-4-yl]butanoic acid; 
     4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2-(2-methoxyethyl)-4-oxobutanoic acid; 
     4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-(2-methoxyethyl)-4-oxobutanoic acid; 
     4-{4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-(2-methoxyethyl)-4-oxobutanoic acid; 
     trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclobutane-carboxylic acid; 
     trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     4-{4′-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     2,2-dimethyl-4-{4′-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid; 
     4-{4′-[(4-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     trans-(1R,2R)-2-{[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid; 
     trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid; 
     4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl) butanoic acid; 
     2-(2-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-oxoethyl)pentanoic acid; 
     trans-2-({4′-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid; 
     trans-2-({4′-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(4-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2-[2-(dimethylamino) ethyl]-4-oxobutanoic acid; 
     2-[2-(dimethylamino)ethyl]-4-{4′-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid; 
     2-[2-(dimethylamino)ethyl]-4-{4′-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid; 
     trans-2-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-ethoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1S,2S)-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     2,2-dimethyl-4-{4′-[(5-nitro-1,3-thiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid; 
     4-(4′-{[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino}-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid; 
     trans-(1R,2R)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1S,2S)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     cis-3-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-yl}carbonyl)cyclohexane-carboxylic acid; 
     cis-3-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid; 
     trans-2-[(4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid;
 trans-(1S,2S)-2-({4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
 
     trans-(1S,2S)-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-[(4′-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]-cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5,7-dimethyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-[(4′-{[6-(methylsulfonyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]-cyclopentane-carboxylic acid; 
     trans-2-({4′-[(5,6-dimethyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     4-{4′-[(6-ethoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     4-{4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid; 
     trans-2-({4′-[(5,7-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid; 
     trans-(1R,2R)-2-[(4′-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)-carbonyl]cyclopentane-carboxylic acid; 
     trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopropane-carboxylic acid; 
     trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid; 
     trans-2-({4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid; 
     trans-2-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid; 
     trans-2-({4′-[(5,7-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid; 
     trans-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid; 
     trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclobutane-carboxylic acid; 
     trans-2-({4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclobutane-carboxylic acid; 
     trans-2-({4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclobutane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-isopropyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-3′-fluoro-1,1′-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1S,2S)-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(5-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}-carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(5,7-dimethyl-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-({4′-[(5,7-difluoro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-[(3′-fluoro-4′-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid; 
     trans-(1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid; 
     trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclobutane-carboxylic acid; 
     trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-3′-fluoro-1,1′-biphenyl-4-yl]carbonyl}cyclobutane-carboxylic acid; 
     trans-2-{[4′-(1,3-benzothiazol-2-ylamino)-3′-fluoro-1,1′-biphenyl-4-yl]carbonyl}cyclopropane-carboxylic acid; 
     trans-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid; 
     trans-(1R,2R)-2-({3′-fluoro-4′-[(6-isopropyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; 
     trans-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentane-carboxylic acid; 
     trans-2-[(3′-fluoro-4′-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)-carbonyl]cyclopentane-carboxylic acid; 
     4-{4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl)butanoic acid; and 
     (1R,2R)-2-[{3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]biphenyl-4-yl}(hydroxy)-methyl]cyclopentanecarboxylic acid. 
   
   
       11 . A compound of Formula (Ia) 
     
       
         
         
             
             
         
       
       wherein 
       Q is O, S, or NR 5 ; 
       A is a linker selected from 
     
     
       
         
         
             
             
         
       
       
         wherein p is 1 or 2 and 
       
     
     
       
         
         
             
             
         
       
       
         wherein m is 0 and n is 1, 2, 3, or 4, or 
         m is 1 and d n is 1, 2, or 3, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 1  and R 2  are independently selected from hydrogen, halo, (C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxy; 
       R 3  is selected from
 hydrogen, 
 (C 1 -C 6 )alkyl optionally substituted by hydroxy, and 
 phenyl optionally substituted with (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or halo; 
 
       R 4  is selected from hydrogen, nitro, and (C 1 -C 6 )alkyl; or 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl, and 
 
       when two of said benzene ring substituents are (C 1 -C 6 )alkyl and are attached to adjacent carbon atoms of the benzene ring, they may be joined together to form a 5-7-membered carbocyclic ring; 
       R 5  is hydrogen or (C 1 -C 6 )alkyl; 
       R 6  is hydrogen; 
       R 7  is hydrogen or
 (C 1 -C 6 )alkyl optionally substituted with
 (C 1 -C 6 )alkoxy, 
 bis[(C 1 -C 3 )alkyl]amino or 
 phenyl optionally substituted with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or cyano; or 
 
 
       R 6  and R 7  are both (C 1 -C 6 )alkyl; or 
       R 6  and R 7  may form, together with the carbon atom to which they are attached, a 3- to 5-membered carbocyclic ring, or
 a 6-membered ring represented by 
 
     
     
       
         
         
             
             
         
       
       
         
           wherein W is CH 2 , C(CH 3 ) 2 , O, NR 9 , S, or SO 2 ; 
         
       
       R 8  is (C 1 -C 6 )alkyl; and 
       R 9  is hydrogen or (C 1 -C 6 )alkyl; 
       or the pharmaceutical salts and esters thereof. 
     
   
   
       12 . A compound of Formula (Ib) 
     
       
         
         
             
             
         
       
       wherein 
       Q is O, S, or NR 5 ; 
       A is a linker selected from 
     
     
       
         
         
             
             
         
       
       
         wherein p is 1 or 2 and 
       
     
     
       
         
         
             
             
         
       
       
         wherein m is 0 and n is 1, 2, 3, or 4, or 
         m is 1 and n is 1, 2, or 3, and 
       
       wherein said linker is optionally substituted by one or two R 8  groups; 
       R 1  and R 2  are independently selected from hydrogen, halo, (C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxy; 
       R 3  is selected from
 hydrogen, 
 (C 1 -C 6 )alkyl optionally substituted by hydroxy, and 
 phenyl optionally substituted with (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or halo; 
 
       R 4  is selected from hydrogen, nitro, and (C 1 -C 6 )alkyl; or 
       R 3  and R 4  may, when taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with up to two substituents selected from
 halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, nitro, cyano, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, bis[(C 1 -C 6 )alkyl]aminocarbonyl, aminosulfonyl, (C 1 -C 6 )alkylaminosulfonyl, bis[(C 1 -C 6 )alkyl]aminosulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylsulfonylamino, hydroxy-(C 2 -C 6 )alkylaminocarbonyl, 1-morpholinylcarbonyl, and 1-piperidinylcarbonyl, and 
 
       when two of said benzene ring substituents are (C 1 -C 6 )alkyl and are attached to adjacent carbon atoms of the benzene ring, they may be joined together to form a 5-7-membered carbocyclic ring; 
       R 5  is hydrogen or (C 1 -C 6 )alkyl; 
       R 6  is hydrogen; 
       R 7  is hydrogen or
 (C 1 -C 6 )alkyl optionally substituted with
 (C 1 -C 6 )alkoxy, 
 bis[(C 1 -C 3 )alkyl]amino or 
 phenyl optionally substituted with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, or cyano; or 
 
 
       R 6  and R 7  are both (C 1 -C 6 )alkyl; or 
       R 6  and R 7  may form, together with the carbon atom to which they are attached, a 3- to 5-membered carbocyclic ring, or
 a 6-membered ring represented by 
 
     
     
       
         
         
             
             
         
       
       
         
           wherein W is CH 2 , C(CH 3 ) 2 , O, NR 9 , S, or SO 2 ; 
         
       
       R 8  is (C 1 -C 6 )alkyl; and 
       R 9  is hydrogen or (C 1 -C 6 )alkyl; 
       or pharmaceutical salts and esters thereof. 
     
   
   
       13 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt or ester, in combination with a pharmaceutically acceptable carrier. 
   
   
       14 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt or ester thereof, in combination with a pharmaceutically acceptable carrier and one or more pharmaceutical agents. 
   
   
       15 . The pharmaceutical composition of  claim 14 , wherein said pharmaceutical agent is an anti-obesity agent selected from the group consisting of β-3 agonists, CB-1 antagonists, neuropeptide Y5 inhibitors, appetite suppressants, and lipase inhibitors. 
   
   
       16 . The pharmaceutical composition of  claim 14 , wherein said pharmaceutical agent is an agent for the treatment of diabetes selected from the group consisting of insulin, insulin derivatives, PPAR ligands, sulfonylurea drugs, α-glucosidase inhibitors, biguanides, PTP-1B inhibitors, DPP-IV inhibitors, 11-beta-HSD inhibitors, GLP-1 and GLP-1 derivatives, GIP and GIP derivatives, PACAP and PACAP derivatives, and secretin and secretin derivatives. 
   
   
       17 . The pharmaceutical composition of  claim 14 , wherein said pharmaceutical agent is an agent for the treatment of lipid disorders selected from the group consisting of HMG-CoA inhibitors, nicotinic acid, fatty acid lowering compounds, lipid lowering drugs, ACAT inhibitors, bile sequestrants, bile acid reuptake inhibitors, microsomal triglyceride transport inhibitors, and fibric acid derivatives. 
   
   
       18 . The pharmaceutical composition of  claim 14 , wherein said pharmaceutical agent is an anti-hypertensive agent selected from the group consisting of β-blockers, calcium channel blockers, diuretics, renin inhibitors, ACE inhibitors, AT-1 receptor antagonists, ET receptor antagonists, and nitrates. 
   
   
       19 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 8 ,  9 ,  10 ,  11 , or  12 , or a pharmaceutically acceptable salt or ester, in combination with a pharmaceutically acceptable carrier. 
   
   
       20 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 8 ,  9 ,  10 ,  11 , or  12 , or a pharmaceutically acceptable salt or ester thereof, in combination with a pharmaceutically acceptable carrier and one or more pharmaceutical agents. 
   
   
       21 . A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 1  or a composition of  claim 13 . 
   
   
       22 . A method of inducing weight loss comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 1  or a composition of  claim 13 . 
   
   
       23 . A method of preventing weight gain comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 1  or a composition of  claim 13 . 
   
   
       24 . A method of treating obesity-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 1  or a composition of  claim 13 . 
   
   
       25 . The method of  claim 24 , wherein said obesity-related disorder is selected from the group consisting of dyslipidemia, cholesterol gallstones, gallbladder disease, gout, cancer, menstrual abnormalities, infertility, polycystic ovaries, osteoarthritis, sleep apnea, hypertriglyceridemia, Syndrome X, type 2 diabetes, atherosclerotic diseases, hyperlipidemia, hypercholesteremia, low HDL levels, hypertension, cardiovascular disease, coronary heart disease, coronary artery disease, cerebrovascular disease, stroke, and peripheral vessel disease. 
   
   
       26 . A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 1  in combination with one or more pharmaceutical agents. 
   
   
       27 . The method of  claim 26 , wherein the compound of  claim 1  and one or more pharmaceutical agents are administered as a single pharmaceutical dosage formulation. 
   
   
       28 . A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition of  claim 14 ,  15 ,  16 ,  17 , or  18 . 
   
   
       29 . A method of treating obesity-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition of  claim 14 ,  15 ,  16 ,  17 , or  18 . 
   
   
       30 . Compounds according to  claim 1  for the treatment and/or prophylaxis of obesity and obesity-related disorders. 
   
   
       31 . Medicament containing at least one compound according to  claim 1  in combination with at least one pharmaceutically acceptable, pharmaceutically safe carrier or excipient. 
   
   
       32 . Use of compounds according to  claim 1  for manufacturing a medicament for the treatment and/or prophylaxis of obesity and obesity-related disorders. 
   
   
       33 . Medicaments according to  claim 31  for the treatment and/or prophylaxis of obesity. 
   
   
       34 . A process for the preparation of a compound of Formula (VIII) comprising the steps of:
 reacting a compound of Formula (II)   
     
       
         
         
             
             
         
       
       
         wherein 
         R is hydrogen or (C 1 -C 6 )alkyl; 
         X is Cl, Br, or I; and 
         R 1  and A are as defined in  claim 1 ; 
       
       with a boronic ester reagent to give a compound of Formula (X) 
     
     
       
         
         
             
             
         
       
       
         wherein 
         R is hydrogen or (C 1 -C 6 )alkyl; and 
         R 1  and A are as defined in  claim 1 ; 
       
       and coupling the compound of Formula (X) with a compound of Formula (IX) 
     
     
       
         
         
             
             
         
       
       
         wherein 
         R 2 , R 3 , R 4 , and Q are as defined in  claim 1 ; 
       
       in the presence of a palladium catalyst, and optionally in the presence of a base, to give the compound of Formula (VIII) 
     
     
       
         
         
             
             
         
       
       
         wherein 
         R is hydrogen or (C 1 -C 6 )alkyl, 
         R 1 , R 2 , R 3 , R 4 , A, and Q are as defined in  claim 1 . 
       
     
   
   
       35 . The process of  claim 34 , wherein the boronic ester reagent is pinnacol borane and the base is potassium carbonate.