Imidazopyridine compounds and uses thereof

Abstract

This invention generally relates to substituted imidazopyridine compounds, particularly substituted 4-(imidazo[1,2-a]pyridin-2-yl)benzamide compounds and salts thereof. This invention also relates to pharmaceutical compositions and kits comprising such a compound, uses of such a compound (including, for example, treatment methods and medicament preparations), processes for making such a compound, and intermediates used in such processes.

We claim: 
     
         1 . A method for treating a disorder associated with P2X3 activity in an animal, wherein the disorder associated with P2X3 activity is selected from the group consisting of multiple sclerosis, Parkinson's disease, Huntington's chorea, Alzheimer's disease, endometriosis, depression, anxiety, a stress-related disorder, and drug addiction, and wherein the method comprises administering to the animal a therapeutically effective amount of a pharmaceutically active compound of Formula (I) or a salt thereof, wherein the compound of Formula (I) is: 
       
         
           
           
               
               
           
         
         R 1  is selected from the group consisting of cyano, halogen, methyl, and ethyl; 
         R 2  is selected from the group consisting of hydrogen, halogen, methyl, and ethyl; 
         R 3  is selected from the group consisting of halogen, methyl, and ethyl; 
         R 4  is selected from the group consisting of hydrogen, halogen, methyl, ethyl, and methoxy; 
         as to R 5  and R 6 ; 
         R 5  and R 6  are independently selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, and hydroxy-C 1 -C 6 -alkyl; or 
         R 5  and R 6 , together with the nitrogen to which they are both attached, form a 5- or 6-member heterocycloalkyl, wherein: 
         the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, and C 1 -C 4 -alkyl; 
         R 7  and R 8  are independently selected from the group consisting of hydrogen and C 1 -C 4 -alkyl; 
         R 9  is selected from the group consisting of C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl-C 3 -C 6 -cycloalkyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkoxy, and C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl; and 
       
       X is selected from a bond, CH 2 , and O. 
     
     
         2 . The method of  claim 1 , wherein R 1  is methyl and R 2  is hydrogen. 
     
     
         3 . The method of  claim 1 , wherein R 3  and R 4  are fluoro. 
     
     
         4 . The method of  claim 1 , wherein X is O. 
     
     
         5 . The method of  claim 1 , wherein the compound corresponds in structure to: 
       
         
           
           
               
               
           
         
       
       and
 R 4  is selected from the group consisting of halogen, methyl, and ethyl. 
 
     
     
         6 . The method of  claim 1 , wherein R 5  is hydrogen and R 6  is C 1 -C 6 -alkyl. 
     
     
         7 . The method of  claim 1 , wherein R 6  is methyl. 
     
     
         8 . The method of  claim 1 , wherein R 7  and R 8  are hydrogen. 
     
     
         9 . The method of  claim 1 , wherein R 9  is C 1 -C 6 -alkoxy. 
     
     
         10 . The method of  claim 1 , wherein R 9  is methoxy. 
     
     
         11 . The method of  claim 1 , wherein the compound corresponds in structure to: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 1 , wherein the compound corresponds in structure to: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 1 , wherein the compound corresponds in structure to: 
       
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 1 , wherein the compound corresponds in structure to: 
       
         
           
           
               
               
           
         
       
     
     
         15 . The method of  claim 1 , wherein the animal is a mammal. 
     
     
         16 . The method of  claim 15 , wherein the mammal is a human. 
     
     
         17 . The method of  claim 1 , wherein the disorder associated with P2X3 activity is endometriosis. 
     
     
         18 . The method of  claim 13 , wherein the disorder associated with P2X3 activity is endometriosis. 
     
     
         19 . The method of  claim 14 , wherein the disorder associated with P2X3 activity is endometriosis. 
     
     
         20 . The method of  claim 1 , wherein the method further comprises administering a second pharmaceutically active compound. 
     
     
         21 . The method of  claim 13 , wherein the method further comprises administering a second pharmaceutically active compound. 
     
     
         22 . The method of  claim 14 , wherein the method further comprises administering a second pharmaceutically active compound.