Compounds for the treatment of mycobacterial infections

Abstract

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

What is claimed is: 
     
       1. A compound of Formula Ia or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is selected from the group consisting of phenyl, substituted phenyl, pyridinyl, and substituted pyridinyl; 
         R 3  is hydrogen or unsubstituted C 1 -C 8  alkyl; 
         R 4  is hydrogen or unsubstituted C 1 -C 8  alkyl; 
         R 2  is: 
       
       
         
           
           
               
               
           
         
         each R 6 , R 7 , R 10  and R 11  is independently selected from the group consisting of hydrogen and unsubstituted C 1 -C 8  alkyl; 
         m is 0;  
         R 5  is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         R 100  is hydrogen or unsubstituted C 1 -C 8  alkyl; and 
         R 100 ′ is hydrogen or unsubstituted C 1 -C 8  alkyl; 
         wherein the substituted phenyl and the substituted pyridinyl are each independently substituted with one or more substituents independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl,-alkoxy alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl,-alkoxycarbonyl alkoxycarbonyl, aryloxycarbonyl, haloalkyl, amino, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxy, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, aralkoxycarbonyl, and sulfonyl. 
       
     
     
       2. The compound of  claim 1  selected from the group consisting of:
 4-(3-aminophenyl)-5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2H-chromen-2-one; and 
 4-phenyl-5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2H-chromen-2-one, or a pharmaceutically acceptable salt of any of thereof. 
 
     
     
       3. The compound of  claim 1 , wherein R 5  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
       4. The compound of  claim 1 , wherein R 3  is unsubstituted C 1 -C 8  alkyl, and R 4  is unsubstituted C 1 -C 8  alkyl, or a pharmaceutically acceptable salt thereof. 
     
     
       5. The compound of  claim 1 , wherein R 1  is phenyl or substituted phenyl, or a pharmaceutically acceptable salt thereof. 
     
     
       6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
       7. A compound selected from the table below, or a pharmaceutically acceptable salt thereof: 
       
         
           
                 
                 
               
                   TABLE A 
                 
                     
                 
                   No 
                   Structure 
                 
                     
                 
                    1 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-4-phenyl-2H- 
                 
                     
                   chromen-2-one 
                 
                     
                 
                    2 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   5,7-dimethyl-4-phenyl-6-(4-(piperidin-l-ylmethyl)phenyl)-2H- 
                 
                     
                   chromen-2-one 
                 
                     
                 
                    3 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   6-(4-((cyclohexylamino )methyl)phenyl)-5,7-dimethyl-4-phenyl-2H- 
                 
                     
                   chromen-2-one 
                 
                     
                 
                    5 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   5,7-dimethyl-6-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-4- 
                 
                     
                   phenyl-2H-chromen-2-one 
                 
                     
                 
                    6 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   4-(3-aminophenyl)-5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)- 
                 
                     
                   2H-chromen-2-one hydrochloride 
                 
                     
                 
                    7 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   4-(4-aminophenyl)-5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)- 
                 
                     
                   2H-chromen-2-one 
                 
                     
                 
                    8 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-4-(3-nitrophenyl)-2H- 
                 
                     
                   chromen-2-one 
                 
                     
                 
                    9 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   methyl 3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo-2H- 
                 
                     
                   chromen-4-yl)benzoate 
                 
                     
                 
                   10 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   N-(3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo-2H- 
                 
                     
                   chromen-4-yl)phenyl)acetamide 
                 
                     
                 
                   11 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   N-(3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo-2H- 
                 
                     
                   chromen-4-yl)phenyl)methanesulfonamide 
                 
                     
                 
                   12 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   ethyl (3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo-2H- 
                 
                     
                   chromen-4-yl)phenyl)caxbamate 
                 
                     
                 
                   13 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                   5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-4-(pyridin- 
                 
                     
                   3-yl)-2H-chromen-2-one 
                 
                     
                 
                   43 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   44 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
       8. The compound of  claim 1 , wherein R 5  is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
       9. The compound of  claim 1 , wherein R 5  is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
       10. The compound of  claim 1 , wherein R 5  is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
       11. The compound of  claim 1 , wherein R 5  is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
       12. The compound of  claim 8 , wherein R 100  is hydrogen, or a pharmaceutically acceptable salt thereof. 
     
     
       13. The compound of  claim 9 , wherein R 100  is hydrogen, or a pharmaceutically acceptable salt thereof. 
     
     
       14. The compound of  claim 10 , wherein R 100  is hydrogen, or a pharmaceutically acceptable salt thereof. 
     
     
       15. The compound of  claim 11 , wherein R 100  is hydrogen, or a pharmaceutically acceptable salt thereof. 
     
     
       16. The compound of  claim 15 , wherein R 100 ′  is hydrogen or methyl, or a pharmaceutically acceptable salt thereof. 
     
     
       17. The compound of  claim 4 , wherein R 3  is unsubstituted C 1 -C 3  alkyl, and R 4  is unsubstituted C 1 -C 3  alkyl, or a pharmaceutically acceptable salt thereof. 
     
     
       18. The compound of  claim 17 , wherein R 3  is methyl and R 4  is methyl, or a pharmaceutically acceptable salt thereof. 
     
     
       19. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of  claim 7 , or a pharmaceutically acceptable salt thereof.