3-amino-1-arylpropyl azaindoles and uses thereof

Abstract

The present invention provides compounds of the formula: or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein p, Ar, R 1 , R 2 , R 3 , R a , R b , R c , R d and R e are defined herein. Also provided are pharmaceutical compositions, methods of using, and methods of preparing the compounds.

1 - 28 . (canceled) 
   
   
       29 . A compound of formula I: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, 
     wherein:
 p is 1 or 2; 
 Ar is:
 pyrrolo[3,2-b]pyridinyl selected from pyrrolo[3,2-b]pyridin-1-yl, pyrrolo[3,2-b]pyridin-2-yl, and pyrrolo[3,2-b]pyridin-3-yl, each optionally substituted; 
 
 R 1  is:
 (a) aryl selected from phenyl and naphthyl, each optionally substituted; or 
 (b) heteroaryl selected from indolyl, pyridinyl, thienyl, furanyl, pyrimidinyl, pyridazinyl, pyrazinyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, quinolinyl and isoquinolinyl, each optionally substituted; 
 (c) optionally substituted arylalkyl; 
 (d) optionally substituted heteroarylalkyl; 
 (e) cycloalkyl; 
 (f) cycloalkylmethyl; or 
 (g) branched alkyl; 
 
 R 2  is:
 (a) hydrogen; 
 (b) alkyl; 
 (c) hydroxyalkyl; 
 (d) alkoxyalkyl; 
 (e) benzyl; or 
 
 or R 2  is a bond that connects the nitrogen atom to one of the ring carbon atoms of Ar; 
 R 3  is:
 (a) hydrogen; 
 (b) alkyl; 
 (c) hydroxyalkyl; 
 (d) alkoxyalkyl; 
 (e) benzyl; or 
 (f) R 2  and R 3  together with the nitrogen to which they are attached may form an optionally substituted four to seven membered ring that optionally includes an additional heteroatom selected from N, O and S; 
 
 R a , R b , R c  and R d  are hydrogen; and: 
 R e  is hydrogen or alkyl. 
 
   
   
       30 . The compound according to  claim 29 , wherein p is 1. 
   
   
       31 . The compound according to  claim 29 , wherein R 1  is aryl, heteroaryl, or cycloalkyl, each of which is optionally substituted. 
   
   
       32 . The compound according to  claim 29 , wherein each of R 2  and R 3  is independently hydrogen or alkyl. 
   
   
       33 . The compound according to  claim 29 , wherein R 2  is a bond that connects the nitrogen atom to one of the ring carbon atoms of Ar. 
   
   
       34 . The compound according to  claim 29  of the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, 
     wherein:
 R 2  is hydrogen, alkyl, or a bond that connects the nitrogen atom to one of the ring carbon atoms of Ar; 
 R 3  is hydrogen or alkyl; and 
 Ar and R 1  are as recited in  claim 29 . 
 
   
   
       35 . The compound according to  claim 34 , wherein R 1  is phenyl, pyridinyl, or cyclohexyl, each of which is optionally substituted. 
   
   
       36 . The compound according to  claim 34  of the formula: 
     
       
         
         
             
             
         
       
     
     wherein
 m is an integer from 0 to 3; 
 each of R 4  and R 5  is independently: hydrogen; alkoxy, cyano, alkyl, halo, —S(O) r R f ; and
 —C(═O)NR g R h ; wherein r is an integer from 0 to 2, and each of R f , R g , and R h  is independently hydrogen or alkyl; 
 
 each R 6  is independently: alkoxy, cyano, alkyl, amino, alkylamino, dialkylamino, halo, —S(O) r R f ; and —C(═O)NR g R h ; wherein r is an integer from 0 to 2, and each of R f , R g , and R h  is independently hydrogen or alkyl; and 
 R 1 , R 2  and R 3  are as recited in  claim 34 . 
 
   
   
       37 . A pharmaceutical composition comprising a compound of  claim 29  and a pharmaceutically acceptable carrier. 
   
   
       38 . A method of treating depression or anxiety, the method comprising administering an effective amount of a compound of  claim 29  to a subject in need thereof.