Bicyclic compounds and use as antidiabetics

Abstract

The present invention relates to novel compounds that are useful in the treatment of metabolic disorders, particularly type II diabetes mellitus and related disorders, and also to the methods for the making and use of such compounds.

1 . A compound of the formula (I) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein
 R 1  is selected from the group consisting of halogen, F 3 C—, NC—, HO—, Ar—, R 7 S—, R 7 S(O)—, R 7 S(O) 2 —, R 7 NHS(O) 2 —, R 7 (C 1-5 alkyl)NS(O) 2 —, R 7 C(O)—, R 7 OC(O)—, R 8 R 9 NS(O) 2 —, R 7 NHC(O)—, R 8 R 9 NC(O)—, R 7 S(O) 2 NH—, and R 7 C(O)NH—; 
 Alk is a direct bond or alkylene of 1 to 3 carbons; 
 rings A and B are independently selected from the group consisting of: 
 
       
       
         
           
           
               
               
           
         
         
           R 2  is a replacement for a hydrogen atom and is independently selected from the group consisting of halogen, —CF 3 , —OH, —C 1-5 alkyl, —C 3-7 cycloalkyl, and —C 1-5 alkoxyl; 
           n is 0, 1, 2, 3, or 4; 
           Q is —O—, —S—, —NH—, —NR 7 —, —S(O)—, or —S(O) 2 —; 
           R 3  and R 4  are independently —H, C 1-5 alkyl, C 3-7 cycloalkyl or C 1-5 alkyl substituted by a 3-7 membered heterocyclic ring or R 3  and R 4  are alkyl and are combined to form a 3-7 membered ring; 
           ring C is: 
         
       
       
         
           
           
               
               
           
         
         
           R 5  is a replacement for a ring hydrogen and is independently selected from the group consisting of halogen, —OH, —CN, C 1-5 alkyl, C 3-7 cycloalkyl, and C 1-5 alkyl substituted by a 3-7 membered heterocyclic ring; 
           p is 0, 1, 2, or 3; 
           R 6  is —C(O)C(O)R 7 , —C(O)OR 10 , —C(O)R 10 , —S(O) 2 C 1-5 alkyl, —S(O) 2 C 3-7 cycloalkyl, —S(O) 2 NR 8 R 9 , Ar, —CH 2 Ar, —C(O)NHC 1-5 alkyl, —C(O)NHC 3-7 cycloalkyl, —C(O)NHC 1-5 alkyl-Ar, or —C(O)NR 10 R 11 ; 
           R 7  is independently selected from the group consisting of
 C 1-5 alkyl, 
 C 3-7 cycloalkyl, 
 phenyl, 
 phenyl(C 1-4 alkylene), 
 a heterocyclic group of 3-7 ring members, and 
 C 1-5 alkyl substituted by a heterocyclic group of 3-7 ring members, 
 
           which group members may be further optionally substituted by one or more of halogen, —OH, C 1-5 alkoxyl, a heteroaryl ring of 5-6 members, —NR 8 R 9 , or —C(O)NR 8 R 9 ; 
           R 8  and R 9  are independently selected from the group consisting of —H, C 1-5 alkyl, C 3-7 cycloalkyl, —C(O)OC 1-5 alkyl and a heterocyclic group of 3-7 members or R 8  and R 9  are alkyl and together combine to form a ring having 4 to 7 ring atoms and optionally containing a heterogroup selected from —O—, —NH— and —N(C 1-5 alkyl)- and wherein said ring having 4 to 7 ring atoms is optionally substituted by oxo; 
           R 10  and R 11  are independently selected from the group consisting of
 C 1-5 alkyl, 
 C 1-5 alkenyl, 
 C 3-7 cycloalkyl, and 
 Ar, 
 
           which group members may be further optionally substituted by halogen, 
           —OH, C 1-5 alkyl, C 1-5 alkoxyl, —Ar, —CH 2 Ar, or —C(O)NR 8 R 9 ; and 
           Ar is aryl or a 5- or 6-membered heteroaryl group, which may be substituted by one or more substituents independently selected from halogen, —CF 3 , C 1-5 alkyl, C 3-7 cycloalkyl, —CN, —NR 8 R 9 , and —NO 2 , with the proviso that said compound is not 5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine or a pharmaceutically acceptable salt thereof. 
         
       
     
     
         2 . The compound according to  claim 1 , wherein R 1  is CH 3 S(O) 2 —, (CH 3 ) 2 CHS(O) 2 —, (—CH 2 CH 2 —)CH—NHC(O)—, (CH 3 ) 2 CHCH 2 NHC(O)—, HOCH 2 CH 2 NHS(O) 2 —, CH 3 OCH 2 CH 2 S(O) 2 —, HOCH 2 CH 2 S(O) 2 —, (—CH 2 CH 2 CH 2 CH 2 —)N—C(O)—, CH 3 OCH 2 CH 2 NHS(O) 2 —, CH 3 OCH 2 C(CH 3 )HNHS(O) 2 —, CH 3 OCH 2 CH 2 CH 2 S(O) 2 —, CH 3 CH 2 OC(O)—, CH 3 S(O)—, C 6 H 5 CH 2 NHC(O)—, C 6 H 5 NHC(O)—, C 6 H 5 C(O)—, HOCH 2 —, CH 3 S(O) 2 NH—, CH 3 CH 2 NHC(O)—, (CH 3 ) 2 NC(O)—, H 2 NC(O)—, (CH 3 CH 2 )NC(O)—, O(—CH 2 CH 2 —) 2 N—C(O)—, (—CH 2 CH 2 CH 2 CH 2 —)CH—NHC(O)—, HOCH 2 CH 2 NHC(O)—, (—CH═N—N═CH—)N—NHC(O)—, (CH 3 ) 3 COC(O)NHCH 2 CH 2 NHS(O) 2 —, O(—CH 2 CH 2 —) 2 N—CH 2 CH 2 NHS(O) 2 —, O(—CH 2 CH 2 —) 2 N—CH 2 CH 2 N(CH 3 )S(O) 2 —, (—CH 2 CH 2 CH 2 C(O)—)N—CH 2 CH 2 CH 2 NHS(O) 2 —, N(—CH 2 CH 2 —) 2 CH—CH 2 CH 2 NHS(O) 2 —, CH 3 OCH 2 CH 2 CH 2 NHS(O) 2 —, CH 3 OCH 2 CH 2 NHC(O)—, CH 3 —, CH 3 S—, CF 3 —, (CH 3 ) 2 CHS—, (CH 3 ) 3 C—, CH 3 CH 2 S(O) 2 —, CH 3 CH 2 CH 2 CH 2 NHC(O)—, O(—CH 2 CH 2 —)N—S(O) 2 —, (CH 3 ) 2 CHNHS(O) 2 —, H 2 NC(O)CH 2 S(O) 2 —, (CH 3 ) 2 NCH 2 CH 2 NHS(O) 2 —, (—CH 2 CH 2 CH 2 CH 2 CH 2 —)N—CH 2 CH 2 NHS(O) 2 —, H 2 NCH 2 CH 2 NHS(O) 2 —, HOCH 2 CH 2 NHC(O)—, O(—CH 2 CH 2 —) 2 N—CH 2 CH 2 CH 2 NHS(O) 2 —, Br—, H 3 COCH 2 CH 2 S—, H 2 NC(O)CH 2 S—, H 3 COCH 2 CH 2 CH 2 S—, (R)—CH 3 S(O)—, or (S)—CH 3 S(O)—. 
     
     
         3 . The compound according to  claim 1 , wherein ring A is of formula i), ii) or iii), with n=0. 
     
     
         4 . The compound according to  claim 1 , wherein ring B is of formula i), ii), iii), iv), v), vi) or vii), with n=0. 
     
     
         5 . The compound according to  claim 1 , wherein R 2  is —F, —CH 3 , —OCH 3 , —OH, —C(O)OCH 3 , or —CH 2 F. 
     
     
         6 . The compound according to  claim 1 , wherein R 6  is —C(O)OC(CH 3 ) 3 , —C(—N═CH—)(═N—CH═)C—CH 2 CH 3 , —C(O)OCH(CH 3 ) 2 , —C(—N═CH—)(═N—CH═)C—Br, —C(═N—)(—O—N═)C—CH(CH 3 ) 2 , —C(═N—)(—O—N═)C—CH 2 CH(CH 3 ) 2 , —C(═N—)(—O—N═)C—CH 3 , —C(—N═CH—)(═N—C(CF 3 )═)C—H, —C(—N═CH—)(═N—CH═)C—CH 2 CH 2 CH 3 , —C(—N═CH—)(═N—CH═)C—F, —C(—N═CH—)(═N—CH═)C—CH(—CH 2 CH 2 —), —CH 2 —C(═CH—CH═)(—CH═CH—)C—OCH(CH 3 ) 2 , —C(—CH═CH—)(═N—N═)C—Cl, —C(O)—CH(—CH 2 CH 2 CH 2 —), —C(O)—C(═CH—CH═)(—S—) C—H, —C(O)—CH═C(CH 3 ) 2 , —C(O)—CH 2 C(CH 3 ) 3 , —CH 2 —C(═CH—CH═)(—CH═CH—)C—F, —CH 2 —C(═CH—CH═)(—C(Cl)═CH—)C—H, —CH 2 —C(═CH—CH═)(—CH═CH—)C—Cl, —CH 2 —C(═CH—CH═)(—CH═C(Cl)—)C—H, —CH 2 —C(═CH—CH═)(—CH═C(F)—)C—H, —CH 2 —C(═CH—CH═)(—CH═CH—)C—CF 3 , —CH 2 —C(═C(F)—CH═)(—CH═C(F)—)C—H, —CH 2 —C(═CH—CH═)(—CH═C(CH 3 )—)C—CH 3 , —CH 2 —C(═CH—CH═)(—CH═CH—)C—CN, —CH 2 —C(═C(F)—CH═)(—CH═C(OCH 3 )—)C—H, —CH 2 —C(═C(Br)—CH═)(—CH═CH—)C—H, —CH 2 —C(═CH—CH═)(—CH═CH—)C—Br, —CH 2 —C(═CH—CH═)(—CH═CH—)C—OCH 3 , —CH 2 —C(═CH—CH═)(—CH═CH—)C—CH 3 , —CH 2 —C(═CH—C(CH 3 )═)(—CH═CH—)C—H, —CH 2 —C(═CH—CH═)(—CH═CH—)C—OC(CH 3 ) 3 , —C(—N═)(═N—O—)C—N(CH 3 ) 2 , —C(—CH═CH—)(═N—N═)C—N(CH 3 ) 2 ), —C(O)—C(═CH—CH═)(—O—)C—H, —C(O)—N(CH 2 CH 3 ) 2 , —C(O)—C(═C—)(—N(CH 3 )—N═)C—CH 3 , —C(O)—C(CH 3 ) 2 CH 2 CH 3 , —C(O)—C(—CH═)(═C(CH 3 )—O—)C—CH 3 , —C(—N═CH—)(═CH—C(Cl)═)N, —C(O)—C(═CH—)(—O—N═)C—H or —C(═CH—CH═)(—N═C(CF 3 )—)C—H, —C(O)C(O)OCH 3 , —C(O)C(O)C(CH 3 ) 3 , —C(O)OCH 2 —C(═CH—CH═)(—CH═CH—) C—H, or —C(O)OCH 2 CH 2 F. 
     
     
         7 . The compound according to  claim 1 , wherein R 7  is —CH 3 , —CH(CH 3 ) 2 , —CH(—CH 2 CH 2 —), —CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 OH, —CH 2 CH 2 OCH 3 , —CH(CH 3 )CH 2 OCH 3 , —CH 2 CH 2 CH 2 OCH 3 , —CH 2 CH 3 , —CH 2 C 6 H 5 , —C 6 H 5 , —CH(—CH 2 CH 2 CH 2 CH 2 —), —N(—CH═N—N═CH—), —CH 2 CH 2 NHC(O)OC(CH 3 ) 3 , —CH 2 CH 2 —N(CH 2 CH 2 ) 2 O, —CH 2 CH 2 CH 2 —N(—C(O)CH 2 CH 2 CH 2 —), —C(═CH—CH═)(—CH═CH—)N, —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 N(CH 3 ) 2 , or —C(CH 3 ) 3 . 
     
     
         8 . The compound according to  claim 1 , wherein R 8  and R 9  are (i) both —CH 3 , (ii) both —H, (iii) both —CH 2 CH 3 , (iv) —H and —C(O)OC(CH 3 ) 3 , or are (v) alkyl and combine to form
 —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 OCH 2 CH 2 —. 
 
     
     
         9 . The compound according to  claim 1 , wherein R 10  and R 11  are —C(CH 3 ) 3 , —CH(CH 3 ) 2 , —CH(—CH 2 CH 2 CH 2 —), —CH═C(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , or —CH 2 CH 3 . 
     
     
         10 . The compound according to  claim 1 , wherein Ar is
 —C(—N═CH—)(═N—CH═)C—CH 2 CH 3 , —C(—N═CH—)(═N—CH═)C—Br, —C(═N—)(—O—N═)C—CH(CH 3 ) 2 ,   —C(═N—)(—O—N═)C—CH 2 CH(CH 3 ) 2 , —C(═N—)(—O—N═)C—CH 3 , —C(—N═CH—)(═N—C(CF 3 )═)C—H,   —C(—N═CH—)(═N—CH═)C—CH 2 CH 2 CH 3 , —C(—N═CH—)(═N—CH═)C—F,   —C(—N═CH—)(═N—CH═)C—CH(—CH 2 CH 2 —), —C(═CH—CH═)(—CH═CH—)C—OCH(CH 3 ) 2 , —C(—CH═CH—)(═N—N═)C—Cl, —C(═CH—CH═)(—S—)C—H,   —C(═CH—CH═)(—CH═CH—)C—F, —C(═CH—CH═)(—C(Cl)═CH—)C—H, —C(═CH—CH═)(—CH═CH—)C—Cl, —C(═CH—CH═)(—CH═C(Cl)—)C—H, —C(═CH—CH═)(—CH═C(F)—)C—H, —C(═CH—CH═)(—CH═CH—)C—CF 3 , —C(═C(F)—CH═)(—CH═C(F)—)C—H, —C(═CH—CH═)(—CH═C(CH 3 )—)C—CH 3 , —C(═CH—CH═)(—CH═CH—)C—CN, —C(═C(F)—CH═)(—CH═C(OCH 3 )—)C—H, —C(═C(Br)—CH═)(—CH═CH—)C—H, —C(═CH—CH═)(—CH═CH—)C—Br, —C(═CH—CH═)(—CH═CH—)C—OCH 3 , —C(═CH—CH═)(—CH═CH—)C—CH 3 , —C(═CH—C(CH 3 )═)(—CH═CH—)C—H, —C(═CH—CH═)(—CH═CH—)C—OC(CH 3 ) 3 , —C(—N═)(═N—O—)C—N(CH 3 ) 2 , —C(—CH═CH—)(═N—N═)C—N(CH 3 ) 2 , —C(═CH—CH═)(—O—)C—H, —C(═C—)(—N(CH 3 )—N═)C—CH 3 , —C(—CH═)(═C(CH 3 )—O—)C—CH 3 , —C(—N═CH—)(═CH—C(Cl)═)N, —C(═CH—)(—O—N═)C—H, —C(═CH—CH═)(—N═C(CF 3 )—)C—H, —C(═CH—CH═)(—N═CH)C—CF 3 , —C(═N—)(—S—N═)C—CH(CH 3 ) 2 , —C(═N—N═)(—S—)C—CH(CH 3 ) 2 , or —C(═N—)(—N═N—)N—CH(CH 3 ) 2 .   
     
     
         11 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof wherein formula (I) is: 
       
         
           
           
               
               
           
         
         wherein
 R 1  is selected from the group consisting of F 3 C—, NC—, Ar—, R 7 S—, R 7 S(O)—, R 7 S(O) 2 —, R 7 NHS(O) 2 —, R 7 (C 1-5 alkyl)NS(O) 2 —, R 7 C(O)—, R 7 OC(O)—, R 8 R 9 NS(O) 2 —, 
 
         R 7 NHC(O)—, and R 8 R 9 NC(O)—;
 ring B is selected from the group consisting of: 
 
       
       
         
           
           
               
               
           
         
         
           R 2  is a replacement for a hydrogen atom and is independently selected from the group consisting of halogen, —CF 3 , C 1-5 alkyl, C 3-7 cycloalkyl, and 
         
         C 1-5 alkoxyl;
 n is 0, 1, 2; 
 R 3  is selected from the group consisting of —H, C 1-5 alkyl, and C 3-7 cycloalkyl; 
 R 6  is —C(O)C(O)R 7 , —C(O)OR 10 , —C(O)R 10 , —S(O) 2 C 1-5 alkyl, —S(O) 2 C 3-7 cycloalkyl, —S(O) 2 NR 8 R 9 , Ar, —CH 2 Ar, —C(O)NHC 1-5 alkyl, —C(O)NHC 3-7 cycloalkyl, —C(O)NHC 1-5 alkyl-Ar, or —C(O)NR 10 R 11 ; 
 R 7  is independently selected from the group consisting of 
 C 1-3 alkyl, 
 C 3-7 cycloalkyl, 
 phenyl, 
 phenyl(C 1-4 alkylene), 
 a heterocyclic group of 3-7 ring members, and 
 C 1-5 alkyl substituted by a heterocyclic group of 3-7 ring members, 
 
         which group members may be further optionally substituted by one or more of halogen, —OH, C 1-3 alkoxyl, a heteroaryl ring of 5-6 members, —NR 8 R 9 , or —C(O)NR 8 R 9 ; 
         R 8  and R 9  are independently selected from the group consisting of —H, C 1-5 alkyl, C 3-7 cycloalkyl, —C(O)OC 1-5 alkyl and a heterocyclic group of 3-7 members or R 8  and R 9  are alkyl and together combine to form a ring having 4 to 7 ring atoms and optionally containing a heterogroup selected from —O—, —NH—, and —N(C 1-3 alkyl)- and wherein said ring having 4 to 7 ring atoms is optionally substituted by oxo; 
         R 10  is selected from the group consisting of
 C 1-3 alkyl, 
 C 1-3 alkenyl, 
 C 3-7 cycloalkyl, and 
 Ar, 
 
         which group members may be further optionally substituted by halogen, 
         —OH, C 1-5 alkyl, C 1-5 alkoxyl, —Ar, —CH 2 Ar, or —C(O)NR 8 R 9 ; and 
         Ar is aryl or a 5- or 6-membered heteroaryl group, which may be substituted by one or more substituents independently selected from halogen, —CF 3 , C 1-5 alkyl, C 3-7 cycloalkyl, —CN, —NR 8 R 9 , and —NO 2 . 
       
     
     
         12 . A compound according to  claim 11  wherein ring B is: 
       
         
           
           
               
               
           
         
       
     
     
         13 . A compound according to  claim 11  wherein ring B is: 
       
         
           
           
               
               
           
         
       
     
     
         14 . A compound according to  claim 11  wherein ring B is: 
       
         
           
           
               
               
           
         
       
     
     
         15 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof wherein formula (I) is: 
       
         
           
           
               
               
           
         
         wherein
 ring B is selected from the group consisting of 
 
       
       
         
           
           
               
               
           
         
         
           R 2  is selected from the group consisting of —H, halogen, —CF 3 , —CH 3 , and 
         
         —CH 2 CH 3 ;
 t is 1 or 2; 
 R 3  is selected from the group consisting of —H, —CH 3 , and —CH 2 CH 3 ; 
 R 6  is —C(O)OR 10 , —C(O)R 10 , or Ar* where Ar* is selected from the group consisting of: 
 
       
       
         
           
           
               
               
           
         
         
           in which R 12  is selected from a group consisting of: 
           C 1-5 alkyl and C 3-7 cycloalkyl and 
           R 13  is selected from a group consisting of 
           —H, halogen, C 1-5 alkyl, and C 3-7 cycloalkyl; 
           R 7a  is independently selected from the group consisting of:
 C 1-5  alkyl and C 3-7 cycloalkyl; 
 
           R 10  is selected from the group consisting of:
 C 1-5 alkyl, 
 C 1-5 alkenyl, 
 C 3-7 cycloalkyl, and 
 Ar, 
 
           which group members may be further optionally substituted by halogen, 
           —OH, C 1-5 alkyl, C 1-5 alkoxyl, —Ar, or —CH 2 Ar; and 
           Ar is aryl or a 5- or 6-membered heteroaryl group, which may be substituted by one or more substituents independently selected from halogen, —CF 3 , C 1-5 alkyl, and C 3-7 cycloalkyl. 
         
       
     
     
         16 . A compound according to  claim 15  wherein R 3  is —CH 3 . 
     
     
         17 . A compound according to  claim 16  wherein R 3  is —CH 3  and the stereochemistry of the stereogenic carbon is (S). 
     
     
         18 . A compound according to  claim 15  wherein R 6  is —C(O)OR 10  and R 10  is selected from the group consisting of:
 C 1-5 alkyl, and 
 C 3-7 cycloalkyl. 
 
     
     
         19 . A compound according to  claim 15  wherein ring B is: 
       
         
           
           
               
               
           
         
       
     
     
         20 . A compound according to  claim 15  wherein ring B is: 
       
         
           
           
               
               
           
         
       
     
     
         21 . A compound selected from
 1,1-Dimethylethyl 4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate,   5-Ethyl-2-[4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyrimidine,   2-[4-({[4′-(Methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]-4-(trifluoromethyl)pyrimidine,   2-[4-({[4′-(Methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]-5-propylpyrimidine,   5-Fluoro-2-[4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyrimidine,   3-Chloro-6-[4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyridazine,   4-Chloro-6-[4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyrimidine,   1-Methylethyl 4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-({[4′-(methylthio)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-({[4′-(trifluoromethyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-[({4′-[(ethyloxy)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({4′-[(1-methylethyl)thio]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   (±)-1-Methylethyl 4-({[4′-(methylsulfinyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-{[(4′-{[(phenylmethyl)amino]carbonyl}-4-biphenyl)oxy]methyl}-1-piperidinecarboxylate,   1-Methylethyl 4-({[4′-(ethylsulfonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-({[4′-(1-pyrrolidinylcarbonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-[({4′-[(phenylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-({[4′-(phenylcarbonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-({[4′-(hydroxymethyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[3-(2-Methylpropyl)-1,2,4-oxadiazol-5-yl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[3-(1,1-Dimethylethyl)-1,2,4-oxadiazol-5-yl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine   1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-[({4′-[(1-methylethyl)sulfonyl]-4-biphenylyl}oxy)methyl]piperidine,   N-Cyclopropyl-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-4-biphenylcarboxamide,   1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-({[4′-(1-pyrrolidinylcarbonyl)-4-biphenylyl]oxy}methyl)piperidine,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-(phenylmethyl)-4-biphenylcarboxamide,   1-(3-Methyl-1,2,4-oxadiazol-5-yl)-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-Methylethyl 4-[({4′-[(ethylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({4′-[(dimethylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-({[4′-(aminocarbonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-[({4′-[(diethylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-({[4′-(4-morpholinylcarbonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-[({4′-[(butylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate   1-Methylethyl 4-[({4′-[(cyclopropylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({4′-[(cyclopentylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-{[(4′-{[(2-methylpropyl)amino]carbonyl}-4-biphenylyl)oxy]methyl}-1-piperidinecarboxylate,   1-Methylethyl 4-{[(4′-{[(2-hydroxyethyl)amino]carbonyl}-4-biphenylyl)oxy]methyl}-1-piperidinecarboxylate,   1-Methylethyl 4-[({4′-[(methylsulfonyl)amino]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   N,N-Dimethyl-3-[4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]-1,2,4-oxadiazol-5-amine,   1-Methylethyl 4-({[4′-(4-morpholinylsulfonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-{[(4′-{[(1-methylethyl)amino]sulfonyl}-4-biphenylyl)oxy]methyl}-1-piperidinecarboxylate,   1-Methylethyl 4-[({4′-[(4H-1,2,4-triazol-4-ylamino)carbonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-{[(4′-{[(2-hydroxyethyl)amino]sulfonyl}-4-biphenylyl)oxy]methyl}-1-piperidinecarboxylate,   1-Methylethyl 4-[({4′-[(1-methylethyl)sulfonyl]-4-biphenylyl}oxy)methyl]-1-piperidinecarboxylate,   1-[(4-Fluorophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(4-Chlorophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(3-Chlorophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(2-Chlorophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(3-Fluorophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   4-({[4′-(Methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-{[4-(trifluoromethyl)phenyl]methyl}piperidine,   1-[(2,5-Difluorophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(3,4-Dimethylphenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-{[2-Fluoro-5-(methyloxy)phenyl]methyl}-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-{[4-(Methyloxy)phenyl]methyl}-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(2-Bromophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(4-Bromophenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   4-{[4-({[4′-(Methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]methyl}benzonitrile,   1-[(3-Methylphenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-[(4-Methylphenyl)methyl]-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   1-({4-[(1-Methylethyl)oxy]phenyl}methyl)-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}-methyl)piperidine,   1-({4-[(1,1-Dimethylethyl)oxy]phenyl}methyl)-4-({[4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine,   2-[4-({[4′-(Methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]-6-(trifluoromethyl)pyridine,   1,1-Dimethylethyl 4-({[3-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-({[2′-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1-Methylethyl 4-({[2′-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   5-Bromo-2-[4-({[2′-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyrimidine,   1-Methylethyl 4-({[3-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-({[2-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-pipendinecarboxylate,   1,1-Dimethylethyl 4-[({5-[4-(methylsulfonyl)phenyl]-2-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({5-[4-(methylsulfonyl)phenyl]-2-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   5-Ethyl-2-{4-[({5-[4-(methylsulfonyl)phenyl]-2-pyridinyl}oxy)methyl]-1-piperidinyl}pyrimidine,   1,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-[({4-[6-(methylsulfonyl)-3-pyridinyl]phenyl}oxy)methyl]-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-[({4-[5-(methylsulfonyl)-2-pyridinyl]phenyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({4-[5-(methylsulfonyl)-2-pyridinyl]phenyl}oxy)methyl]-1-piperidinecarboxylate,   5-Ethyl-2-{4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}pyrimidine,   1-Methylethyl 4-({[6-(4-{[2-(methoxy)ethyl]sulfonyl}phenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-{[(6-{4-[(2-hydroxyethyl)sulfonyl]phenyl}-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate,   2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine,   1-Methylethyl 4-{[(6-{4-[(2-amino-2-oxoethyl)sulfonyl]phenyl}-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-({[6-(4-{[3-(methoxy)propyl]sulfonyl}phenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate,   5-({[1-(2-Furanylcarbonyl)-4-piperidinyl]methyl}oxy)-2-[4-(methylsulfonyl)phenyl]pyridine,   2-[4-(Methylsulfonyl)phenyl]-5-({[1-(2-thienylcarbonyl)-4-piperidinyl]methyl}oxy)pyridine,   5-({[1-(Cyclobutylcarbonyl)-4-piperidinyl]methyl}oxy)-2-[4-(methylsulfonyl)phenyl]pyridine,   5-({[1-(3-Methyl-2-butenoyl)-4-piperidinyl]methyl}oxy)-2-[4-(methylsulfonyl)phenyl]pyridine,   5-({[1-(2,2-Dimethylbutanoyl)-4-piperidinyl]methyl}oxy)-2-[4-(methylsulfonyl)phenyl]pyridine,   N,N-Diethyl-4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxamide,   5-({[1-(3,3-Dimethylbutanoyl)-4-piperidinyl]methyl}oxy)-2-[4-(methylsulfonyl)phenyl]pyridine,   5-[({1-[(1,3-Dimethyl-1H-pyrazol-5-yl)carbonyl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   5-[({1-[(2,5-Dimethyl-3-furanyl)carbonyl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   5-({[1-(5-Isoxazolylcarbonyl)-4-piperidinyl]methyl}oxy)-2-[4-(methylsulfonyl)phenyl]pyridine,   1-Methylethyl 4-[({6-[4-(1-pyrrolidinylcarbonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({6-[4-(4-morpholinylcarbonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-({[6-(4-{[(2-hydroxyethyl)amino]carbonyl}phenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-[({6-[4-({[2-(methyloxy)ethyl]amino}carbonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-{4-[(1-methylethyl)sulfonyl]phenyl}pyridine,   1-Methylethyl 4-{[(6-{4-[(1-methylethyl)sulfonyl]phenyl}-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate,   1-Methylethyl 4-({[2-(methoxy)-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate,   N-(2-Hydroxyethyl)-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-4-biphenylsulfonamide,   N-(2-Hydroxyethyl)-4-{5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-pyridinyl}benzenesulfonamide,   2,5-Difluoro-N-(2-hydroxyethyl)-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-4-biphenylsulfonamide,   5-[({1-[5-(1-Methylethyl)-1,2,4-oxadiazol-3-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   1,1-Dimethylethyl {2-[({4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-4-biphenylyl}sulfonyl)amino]ethyl}carbamate,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(4-morpholinyl)ethyl]-4-biphenylsulfonamide,   N-[2-(Dimethylamino)ethyl]-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-4-biphenylsulfonamide,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(1-piperidinypethyl]-4-biphenylsulfonamide,   N-(2-aminoethyl)-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-4-biphenylsulfonamide,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(methoxy)ethyl]-4-biphenylsulfonamide,   (±)-4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[1-methyl-2-(methoxy)ethyl]-4-biphenylsulfonamide,   N-Methyl-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(4-morpholinyl)ethyl]-4-biphenylsulfonamide,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[3-(4-morpholinyl)propyl]-4-biphenylsulfonamide,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[3-(2-oxo-1-pyrrolidinyl)propyl]-4-biphenylsulfonamide,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(4-pyridinyl)ethyl]-4-biphenylsulfonamide,   4′-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[3-(methoxy)propyl]-4-biphenylsulfonamide,   1-Methylethyl 4-({[6-(4-{[(2-hydroxyethyl)amino]sulfonyl}phenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-[({6-[4-({[2-(methoxy)ethyl]amino}sulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({6-[2-fluoro-4-({[2-(methoxy)ethyl]amino}sulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   2-Fluoro-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(methoxy)ethyl]-4-biphenylsulfonamide,   2,5-Difluoro-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(methoxy)ethyl]-4-biphenylsulfonamide,   2-Fluoro-N-(2-hydroxyethyl)-4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-4-biphenylsulfonamide,   1,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridazinyl}oxy)methyl]-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-[({5-[4-(methylsulfonyl)phenyl]-2-pyrimidinyl}oxy)methyl]-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-[({2-[4-(methylsulfonyl)phenyl]-5-pyrimidinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({2-[4-(methylsulfonyl)phenyl]-5-pyrimidinyl}oxy)methyl]-1-piperidinecarboxylate,   5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyrimidine,   1-Methylethyl 4-[({2-fluoro-4-[5-(methylsulfonyl)-2-pyridinyl]phenyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-{[(6-{4-[(methylsulfonyl)methyl]phenyl}-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate,   1-Methylethyl 4-[({2-fluoro-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)methyl]-1-piperidinecarboxylate,   Methyl 3-{[(1-{[(1-methylethyl)oxy]carbonyl}-4-piperidinyl)methyl]oxy}-6-[4-(methylsulfonyl)phenyl]-2-pyridinecarboxylate,   1-Methylethyl 4-[({2-(fluoromethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   Methyl {4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}(oxo)acetate,   1-{4-[({6-[2-Fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}-3,3-dimethyl-1-oxo-2-butanone,   (±)-Phenylmethyl 4-[1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)ethyl]-1-piperidinecarboxylate,   (±)-1-Methylethyl 4-[1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)ethyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[(1S)-1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)ethyl]-1-piperidinecarboxylate,   (±)-1-Methylethyl 4-[1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)propyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[(1R)-1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)propyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[(1S)-1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)propyl]-1-piperidinecarboxylate,   2-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine,   (±)-5-[(1-{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   5-[((1R)-1-{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   5-[((1S)-1-{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   2-Fluoroethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   5-Fluoro-2-{4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}pyrimidine,   5-Fluoro-2-{4-[({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)methyl]-1-piperidinyl}pyrimidine,   (±)-5-Fluoro-2-{4-[1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)ethyl]-1-piperidinyl}pyrimidine,   5-Fluoro-2-{4-[(1S)-1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)ethyl]-1-piperidinyl}pyrimidine,   5-Fluoro-2-{4-[(1R)-1-({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)ethyl]-1-piperidinyl}pyrimidine,   (±)-2-[(1-{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine,   2-[((1R)-1-{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine,   2-[((1S)-1-{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine,   2-[4-(Methylsulfonyl)phenyl]-5-[({1-[5-(trifluoromethyl)-2-pyridinyl]-4-piperidinyl}methyl)oxy]pyridine,   (±)-1,1-Dimethylethyl 4-[1-({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate,   2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyrazine,   (±)-1-Methylethyl 4-[1-({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[(1S)-1-({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[(1R)-1-({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({5-[2-fluoro-4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)methyl]-1-piperidinecarboxylate,   2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[((1S)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]pyrazine,   1-Methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate,   (±)-1-Methylethyl 4-[({6-[2-fluoro-4-(methylsulfinyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-({[4′-(methylsulfonyl)-4-biphenylyl]thio}methyl)-1-piperidinecarboxylate,   5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridine,   1,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}amino)methyl]-1-piperidinecarboxylate,   (±)-1-Methylethyl 4-[({6-[4-(methylsulfinyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   (R)-1-Methylethyl 4-[({6-[4-(methylsulfinyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   (S)-1-Methylethyl 4-[({6-[4-(methylsulfinyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   (±)-2-[2-Fluoro-4-(methylsulfinyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine,   (R)-2-[2-Fluoro-4-(methylsulfinyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine,   (S)-2-[2-Fluoro-4-(methylsulfinyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine,   (R)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridine,   (S)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridine,   1-Methylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}amino)methyl]-1-piperidinecarboxylate,   5-[({1-[3-(1-Methylethyl)-1,2,4-thiadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-thiadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine,   5-[({1-[5-(1-Methylethyl)-1,3,4-thiadiazol-2-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   1,1-Dimethylethyl 4-[({6-[2-methyl-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   1-Methylethyl 4-[({6-[2-methyl-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate,   5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[2-methyl-4-(methylsulfonyl)phenyl]pyridine,   2-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-5-[2-methyl-4-(methylsulfonyl)phenyl]pyrazine,   5-[({1-[2-(1-Methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine,   5-[((1S)-1-{1-[2-(1-Methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethyl)oxy]-2-[4-(methylsulfonyl)phenyl],   2-[((1S)-1-{1-[2-(1-Methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine, and   2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[((1S)-1-{1-[2-(1-methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethyl)oxy]pyridine   or a pharmaceutically acceptable salt thereof.   
     
     
         22 . A compound selected from
 1,1-Dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-({[6-(4-{[2-(methoxy)ethyl]thio}phenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl 4-{[(6-{4-[(2-amino-2-oxoethyl)thio}phenyl]-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate,   1,1-Dimethylethyl 4-({[6-(4-{[3-(methoxy)propyl]thio}phenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate,   1-Methylethyl-4-{[(6-{4-[(ethyloxy)carbonyl]phenyl}-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate,   4-({[2-Hydroxy-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate, and   1,1-Dimethylethyl 4-({[2-(4-bromophenyl)-5-pyrimidinyl]oxy}methyl)-1-piperidinecarboxylate   1-Methylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate   5-Ethyl-2-{4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}pyrimidine   1-Methylethyl 4-[(1S)-1-({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate   1-Methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate   2-[((1S)-1-{1-[2-(1-Methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine   2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[((1S)-1-{1-[2-(1-methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethyl)oxy]pyridine,   or a pharmaceutically acceptable salt thereof.   
     
     
         23 . A method for the treatment of metabolic disorder or condition comprising the administration of a compound according to  claim 1  or a salt thereof, wherein the metabolic disorder or condition is selected from the group consisting of diabetes, obesity, glucose intolerance, insulin resistance, metabolic syndrome X, hyperlipidemia, hypercholesterolemia, and arthersclerosis. 
     
     
         24 . A pharmaceutical composition comprising a compound of  claim 1  or a salt, solvate, or physiological functional derivative thereof and at least one pharmaceutically acceptable carrier, diluent, or excipient.