Substituted Azepine Derivatives As Serotonin Receptor Modulators

Abstract

The present invention generally relates to compounds and pharmaceutical compositions containing the compounds. More specifically, compounds of the present invention are hexahydroazepinoindole and octahydroazepinoindole compounds. These compounds are serotonin receptor (5-HT) ligands and are useful for treating diseases, disorders, and conditions wherein modulation of the activity of serotonin receptors (5-HT) is desired (e.g. anxiety, depression and obesity).

1 . A compound of the formula 
     
       
         
         
             
             
         
       
       where X is S, O or NR 5 ; 
       R 1  and R 2  are independently selected from the group consisting of H, halogen, C 1-8  alkyl, C 1-8  alkylaryl, C 1-8  alkyl heteroaryl, C 2-8  alkenyl, perhalo alkyl, CN, OR 5 , SR 5 , N(R 5 ) 2 , CON(R 5 ) 2 , NR 5 COR 5 , NR 5 CO 2 R 5 , SO 2 N(R 5 ) 2 , NR 5 SO 2 R 5 , aryl and heteroaryl, wherein said aryl or heteroaryl can be optionally substituted with up to three substituents selected from alkyl, halogen and alkoxy; 
       R 3  is selected from the group consisting of H, C 1-8  alkyl, C 1-8  alkylaryl, C 1-8  alkylheteroaryl, OR 5 , —CH 2 —O—C 1-8  alkyl, —CH 2 OH, —COO—C 1-8  alkyl, —CON(R 5 ) 2 , and aryl; 
       R 3a  is H or R 3  and R 3a  taken together are CH 2 CH 2 — or 
       R 2  and R 3  form a 5- or 6-member ring; 
       R 4  is selected from the group consisting of H, C 1-8  alkyl, C 1-8  alkylaryl, C 1-8  alkylheteroaryl, OR 5 , —CH 2 —O—C 1-8  alkyl, —CH 2 OH, —COO—C 1-8  alkyl, and —CON(R 5 ) 2 ; 
       R 4a  is H or R 4  and R 4a  taken together are —CH 2 CH 2 —; 
       R 5  is selected from the group consisting of H, C 1-8  alkyl, C 1-8  alkylaryl, C 1-8  alkylheteroaryl, aryl, heteroaryl, and perhaloalkyl; with the provisos that at least one of R 1 , R 2 , R 3 , R 3a , R 4 , and R 4a  must be other than hydrogen; 
       if R 3  is OH, then at least one of R 1 , R 2 , R 4 , and R 4a  must be other than hydrogen; and 
       if X is O, then at least one of R 3 , R 3a , R 4 , and R 4a  must be other than hydrogen; 
     
     or a pharmaceutically acceptable salt thereof. 
   
   
       2 . A pharmaceutical composition comprising at least one compound of  claim 1  and a pharmaceutically acceptable carrier.