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.

1 . A method for treating a disorder associated with P2X3 activity in an animal, wherein the method comprises administering to the animal a therapeutically effective amount of a first pharmaceutically active compound of Formula (I) or a salt thereof, and a second pharmaceutically active compound, 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 selected from the group consisting of pain, chronic cough, a urinary tract disorder, multiple sclerosis, Parkinson's disease, Huntington's chorea, Alzheimer's disease, endometriosis, depression, anxiety, a stress-related disorder, and drug addiction. 
     
     
         18 . The method of  claim 1 , wherein the second pharmaceutically active compound is selected from the group consisting of antidepressants, antipsychotics, anxiolytics, anticonvulsants, Alzheimer's therapies, Parkinson's therapies, urinary incontinence therapies, insomnia therapies, mood stabilizers, obesity medications, ADHD medications, and agents used to treat substance abuse disorders, dependence, and withdrawal. 
     
     
         19 . (canceled) 
     
     
         20 . A compound of Formula (I) or a salt thereof, wherein 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; 
         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.