IMIDAZO[1,2-a]PYRIDINE COMPOUNDS

Abstract

Imidazo[1,2-a]pyridines are disclosed. Compounds of the invention are useful therapeutic agents and their inclusion in pharmaceutical formulations and use in methods of treatment are disclosed.

1 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3  and R 4  are each members independently selected from H, D, halogen, hydroxyl, dialkylamino, cyano, sulfonamide, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, wherein a member selected from R 1  and R 3 , R 2  and R 4  and a combination thereof are optionally joined in a ring; 
 R 5  and R 6  are each a member independently selected from H, D, F, hydroxyl, substituted or unsubstituted alkoxy and lower alkyl, wherein R 5  and R 6  are optionally joined into a ring; 
 Q is a member selected from: 
 
       
         
           
           
               
               
           
         
       
       wherein
 ring A 1  is an unsubstituted 4, 6 or 7 member monocyclic, a substituted 4, 5, 6 or 7 member monocyclic or an optionally substituted 8, 9, 10, 11 or 12 member bicyclic ring comprising 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S; 
 ring A 2  is a substituted 4, 5, 6 or 7 member monocyclic or an optionally substituted 8, 9, 10, 11 or 12 member bicyclic ring comprising 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S; 
 ring A 3  is chosen from substituted or unsubstituted thiadiazolyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted oxadiazolyl, substituted or unsubstituted triazinyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted triazolyl, substituted or unsubstituted indolinyl, substituted or unsubstituted furopyrrolyl, substituted or unsubstituted indolyl, substituted or unsubstituted isoindolyl, substituted or unsubstituted benzotriazolyl, substituted or unsubstituted benzooxazolyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted tetrazolyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted thiadiazolyl, substituted or unsubstituted indazolyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted benzooxazinyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzothiadiazonyl, substituted or unsubstituted thiopheneyl, substituted or unsubstituted quinolinyl, substituted or unsubstituted quinazolinyl, substituted or unsubstituted oxazolidinyl and substituted or unsubstituted azetidinyl; 
 X is selected from O, S and NR 7 , wherein R 7  is selected from H, D, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; 
 Y is a member selected from a bond, (CR 8 R 9 ) n , O, S, NR 10 R 11 , S(O), S(O) 2 , S(O)pNR 10 R 11 , (CR 8 R 9 ) n G(CR 8 R 9 ) m    
 wherein
 G is a member selected from a bond and O; 
 m and n are independently selected integers from 0 to 4; 
 each R 8 , R 9  and R 10  are independently selected from H, D, substituted or unsubstituted alkyl, acyl, SO 2 R 8a , OR 8a , COOR 8a , and CONR 8a R 8b , wherein R 8a  and R 8b  are independently selected from H, D, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, wherein a member selected from R 8  and R 9 , R 8a  and R 8b  and a combination thereof are optionally joined in a ring; 
 R 11  is selected from a bond and NR 11a    
 wherein
 R 11a  is selected from H, D, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; and 
 
 
 Z is. 
 
     
     
         2 . The compound of  claim 1 , wherein R 5  and R 6  are both H. 
     
     
         3 . The compound of  claim 1 , wherein Q is 
       
         
           
           
               
               
           
         
         and ring A 1  is selected from substituted or unsubstituted heteroaryl. 
       
     
     
         4 . (canceled) 
     
     
         5 . The compound of  claim 3  wherein ring A 1  is a member selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1  wherein Q is 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 6  wherein Q is a member selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 1  wherein Q is 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 8  wherein Q is a member selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 1  wherein A 1 , A 2  or A 3  is selected from substituted or unsubstituted thiadiazolyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted oxadiazolyl, substituted or unsubstituted triazinyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted triazolyl, substituted or unsubstituted benzoimidazolyl, substituted or unsubstituted indolinyl, substituted or unsubstituted furopyrrolyl, substituted or unsubstituted indolyl, substituted or unsubstituted benzotriazolyl, substituted or unsubstituted benzooxazolyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted tetrazolyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted indazolyl, substituted or unsubstituted diazolyl, substituted or unsubstituted purinyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted imidazopyridinyl, substituted or unsubstituted benzooxazinyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted benzyl, substituted or unsubstituted benzothiadiazonyl, substituted or unsubstituted thiopheneyl, substituted or unsubstituted quinolinyl, substituted or unsubstituted quinazolinyl, substituted or unsubstituted oxazolidinyl, substituted or unsubstituted imidazolidinyl and substituted or unsubstituted azetidinyl. 
     
     
         11 .- 16 . (canceled) 
     
     
         17 . A compound having a structure selected from: 
       
         
           
           
               
               
           
         
       
       wherein
 R 16  and R 17  are independently selected from H, D, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl and NR 18 R 19  wherein R 18  and R 19  are substituted or unsubstituted alkyl, and R 18  and R 19  are optionally joined in a ring; 
 a is an integer selected from 1, 2 and 3; and 
 Q is selected from substituted or unsubstituted heterocycloalkyl and substituted or unsubstituted heteroaryl 
 
     
     
         18 . The compound of  claim 17  wherein Q has the structure:
   —R 20 -R 21  
 
 wherein R 20  is selected from a bond and NH; and 
 R 21  is selected from substituted or unsubstituted heterocycloalkyl and substituted or unsubstituted heteroaryl 
 
     
     
         19 . The compound of  claim 18  wherein Q has a structure selected from: 
       
         
           
           
               
               
           
         
       
     
     
         20 .- 50 . (canceled) 
     
     
         51 . The compound according to  claim 1  as a pharmaceutically acceptable salt. 
     
     
         52 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         53 . A method for treating or preventing a disease or condition selected from the group consisting of anxiety disorders, psychiatric disorders, convulsive disorders, aggressive behavior, muscle spasms or tension, depressive or bipolar disorders, cognitive disorders, sleeping disorders, neurodegenerative eye diseases, neurodegeneration, pain, schizophrenia, emesis and eating disorders, comprising administering to a patient a therapeutically effective amount of the composition of  claim 52 . 
     
     
         54 . A method for modulating GABA A  receptor subtypes comprising administering to a patient a therapeutically effective amount of a compound according to the composition of  claim 52 . 
     
     
         55 . A method for inhibiting a benzodiazepine receptor comprising administering to a patient a therapeutically effective amount of a compound according to  claim 1 .