Arylthiobenzylpiperidine Derivatives

Abstract

This invention is directed to Arylthiobenzylpiperidine derivatives which are ligands at the MCH1 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition made by admixing a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject a therapeutically effective amount of a compound of the subject invention. This invention also provides a method of treating a subject suffering from obesity which comprises administering to the subject a therapeutically effective amount of a compound of the subject invention.

1 . A compound having the structure: 
       
         
           
           
               
               
           
         
         wherein each X 1 , X 2 , X 3 , X 4  and X 5  is independently CR 1  or N, provided that if one X is N then the remaining X are each CR 1 ; 
         wherein each U 1 , U 2 , U 3  and U 4  is independently CH or N, provided that if one U is N then the remaining U are each CH; 
         wherein each Y 1 , Y 2 , Y 3  and Y 4  is independently CR 7  or N, provided that if one Y is N then the remaining Y are each CR 7 ; 
         wherein G is hydrogen or —C(O)D; 
         wherein D is 
       
       
         
           
           
               
               
           
         
         wherein Z is —N(R 5 ) or —O—; 
         wherein each A is independently H or straight chained or branched C 1 -C 4  alkyl; 
         wherein B is CH or N; 
         wherein each R 1  is independently H, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  fluoroalkyl, straight chained or branched C 1 -C 7  alkoxy, F, Cl, Br or I; 
         wherein R 2  is H or straight chained or branched C 1 -C 4  alkyl; 
         wherein R 3  is H or straight chained or branched C 1 -C 4  alkyl; 
         or wherein if B is N, then the R 2  moiety, B, the R 3  moiety and a bond formed between the R 2  moiety and the R 3  moiety form: 
       
       
         
           
           
               
               
           
         
         or wherein if B is CH, then the R 2  moiety, B, the R 3  moiety and a bond formed between the R 2  moiety and the R 3  moiety form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; 
         wherein R 4  is H, straight chained or branched C 1 -C 4  alkyl, straight chained or branched C 1 -C 4  fluoroalkyl or F; 
         wherein R 5  is H or straight chained or branched C 1 -C 4  alkyl; 
         wherein each R 6  is independently straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  fluoroalkyl, straight chained or branched C 1 -C 7  alkoxy, F, Cl, Br or I; 
         wherein each R 7  is independently H, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  fluoroalkyl, straight chained or branched C 1 -C 7  alkoxy, F, Cl, Br or I; 
         wherein R 8  is H, straight chained or branched C 1 -C 4  alkyl, straight chained or branched C 1 -C 4  fluoroalkyl or F; 
         wherein m is an integer from 0 to 4 inclusive; 
         wherein n is an integer from 0 to 2 inclusive; 
         wherein p is an integer from 0 to 4 inclusive; 
         wherein q is an integer from 0 to 3 inclusive; 
         wherein r is 1 or 2; 
         wherein s is an integer from 0 to 4 inclusive; 
         wherein t is an integer from 2 to 4 inclusive; 
         wherein v is an integer from 0 to 2 inclusive; and 
         wherein w is an integer from 1 to 5 inclusive; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound of  claim 1 , having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 2 , wherein m is 0 or 1 and R 6  is methyl, F or Cl. 
     
     
         4 . The compound of  claim 3 , wherein each X 1 , X 2 , X 3 , X 4  and X 5  is CR 1 , and each Y 1 , Y 2 , Y 3  and Y 4  is CR 7 . 
     
     
         5 . The compound of  claim 4 , wherein each R 1  is independently H, methyl, F or Cl, and each R 7  is independently H, F or methyl. 
     
     
         6 . The compound of  claim 5 , wherein D is 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 6 , wherein D is 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 7 , wherein B is N, then the R 2  moiety, B, the R 3  moiety and the bond formed between the R 2  moiety and the R 3  moiety form: 
       
         
           
           
               
               
           
         
       
       or wherein B is CH then the R 2  moiety, B, the R 3  moiety and the bond formed between the R 2  moiety and the R 3  moiety form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; 
     
     
         9 . The compound of  claim 7 , wherein B is N, and R 2  and R 3  each are independently H, methyl or ethyl. 
     
     
         10 . The compound of  claim 9 , wherein s is 1 or 2. 
     
     
         11 . The compound of  claim 7 , wherein R 2  and R 3  are each independently H, methyl or ethyl and B is CH. 
     
     
         12 . The compound of  claim 11 , wherein each A is independently H, methyl or ethyl; s is 0 or 1; and m is 0. 
     
     
         13 . The compound of  claim 6 , wherein D is 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 13 , wherein each A is independently H, methyl or ethyl; Z is O; s is 0 or 1; and m is 0. 
     
     
         15 . The compound of  claim 14 , wherein R 2  and R 3  are independently H, methyl or ethyl. 
     
     
         16 . The compound of  claim 6 , wherein D is 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 16 , wherein the R 2  moiety, N, the R 3  moiety and the bond formed between the R 2  moiety and the R 3  moiety form: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 16 , wherein R 2  and R 3  are each independently H, methyl or ethyl. 
     
     
         19 - 27 . (canceled) 
     
     
         28 . A pharmaceutical composition comprising a therapeutically amount of a compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         29 . (canceled) 
     
     
         30 . A method of treating a subject suffering from depression comprising administering to the subject a therapeutically effective amount of the compound of  claim 1 . 
     
     
         31 . A method of treating a subject suffering from anxiety comprising administering to the subject a therapeutically effective amount of the compound of  claim 1 . 
     
     
         32 . A method of treating a subject suffering from obesity comprising administering to the subject a therapeutically effective amount of the compound of  claim 1 .