Bicyclic Indolyl Derivatives and Methods for Their Use as Serotonergic Agents

Abstract

Bicyclic indolyl derivatives and compositions containing such compounds are disclosed. Methods of using the bicyclic indolyl derivatives and compositions containing such composition as serotonergic agents, such as in the treatment of depression and anxiety, are also disclosed. In addition, processes for the preparation of bicyclic indolyl derivatives are disclosed.

1 . (canceled)  
   
   
       2 . A method according to  claim 8 ,  9 , or  21   wherein:    R 2  is H or methyl.    
   
   
       3 . A method according to  claim 8 ,  9 , or  21 , 
 wherein: 
 R 1  is H or alkyl; and  
 n is 1.  
   
   
   
       4 . A method according to  claim 8 ,  9 , or  21 , wherein said compound is selected from the group consisting of: 
 (S)-N-{(2R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]propyl}-N-pyridin-2-ylbicyclo[2.2.2]octane-2-carboxamide;    (R)-N-{(2R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]propyl}-N-pyridin-2-ylbicyclo[2.2.2]octane-2-carboxamide;    N-{(2R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]propyl}-7-methyl-N-pyridin-2-yl-bicyclo[2.2.1]heptane-7-carboxamide;    N-{(2R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]propyl}-7-methyl-N-pyridin-2-yl-bicyclo[2.2.1]heptane-7-carboxamide; and    prodrugs, N-oxides and pharmaceutically-acceptable salts thereof.    
   
   
       5 . A method according to  claim 8 ,  9 , or  21 , wherein said compound is selected from the group consisting of: 
 (S)-N-{(2R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]propyl}-N-pyridin-2-ylbicyclo[2.2.2]octane-2-carboxamide;    (R)-N-{(2R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]propyl}-N-pyridin-2-ylbicyclo[2.2.2]octane-2-carboxamide; and    prodrugs, N-oxides and pharmaceutically-acceptable salts thereof.    
   
   
       6 . (canceled)  
   
   
       7 . (canceled)  
   
   
       8 . A method of binding 5-HT 1A  receptors in a patient in need thereof, 
 comprising the step of administering to the patient an effective amount of the compound of formula (I):                          or a prodrug, stereoisomer, N-oxide or pharmaceuticallv-acceptable salt thereof;    wherein: 
 R 1  is H, halo or alkyl;  
 R 2  is H or lower alkyl; and  
 n is 0 or 1.  
   
   
   
       9 . A method of antagonizing 5-HT 1A  receptors in a patient in need thereof, 
 comprising the step of administering to the patient an effective amount of the compound of formula (I):                          or a prodrug, stereoisomer, N-oxide or pharmaceutically-acceptable salt thereof;    wherein: 
 R 1  is H, halo or alkyl;  
 R 2  is H or lower alkyl; and  
 n is 0 or 1.  
   
   
   
       10 - 20 . (canceled)  
   
   
       21 . A method for treating prostate cancer in a patient in need thereof, comprising the step of: 
 administering to the patient an effective amount of the compound of formula (I):                          or a prodrug, stereoisomer, N-oxide or pharmaceutically-acceptable salt thereof;    wherein: 
 R 1  is H, halo or alkyl;  
 R 2  is H or lower alkyl; and  
 n is 0 or 1.  
   
   
   
       22 . (canceled)