2-pyridone antimicrobial compositions

Abstract

Disclosed herein are compounds of Formula I wherein R 1 , R 2 , X, and Y are defined herein. These compounds are type II topoisomerase inhibitors and can be used in methods for treating infections caused by gram-positive pathogens, gram-negative pathogens, and drug-resistant strains thereof.

1 - 30 . (canceled) 
     
     
         31 . A method of treating a subject infected by an organism selected from  Enterococcus faecalis, Streptococcus pneumonia , and  Haemophilus influenza , wherein the method comprises administering to the subject a compound of the formula, 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein
 Y is phenyl substituted by
 one 5-6 membered heterocyclyl optionally substituted with amino; or 
 one to five groups that are each independently halogen, —C 1-8  alkyl-NH 2 , C 1-8  alkyl, —N(R Y1 ) 2 , —C(O)OR Y1 , or —C(O)N(R Y1 ) 2 ,
 wherein each R Y1  is independently hydrogen or C 1-8  alkyl. 
 
 
 
       
     
     
         32 . A method according to  claim 31 , wherein Y is phenyl substituted with
 a) one group which is —NH 2  or —C 2-8  alkyl-NH 2 , and   b) two groups that are each independently halogen, C 1-8  alkyl, —C(O)OR Y1 , or —C(O)N(R Y1 ) 2 .   
     
     
         33 . A method according to  claim 31 , wherein Y is phenyl substituted with
 a) one group which is —NH 2  or —CH 2 NH 2 , and   b) two groups that are each halogen.   
     
     
         34 . A method according to  claim 31 , wherein the compound is:
 8-(3-fluoro-4-amino-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid;   8-(3-amino-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid;   8-(4-amino-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid;   8-(4-carbamoyl-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid;   8-[(3S)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid;   8-(4-(aminomethyl)phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid;   8-(2,5-difluoro-4-amino-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid;   8-(4-carboxy-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid;   or a pharmaceutically acceptable salt thereof.   
     
     
         35 . A method according to  claim 31 , wherein the compound is a pharmaceutically acceptable salt, and the pharmaceutically acceptable salt is a potassium salt. 
     
     
         36 . A method according to  claim 34 , wherein the compound is a pharmaceutically acceptable salt, and the pharmaceutically acceptable salt is a potassium salt. 
     
     
         37 . A method according to  claim 31 , wherein the compound is 8-(2,5-difluoro-4-amino-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid or a pharmaceutically acceptable salt thereof. 
     
     
         38 . A method according to  claim 31 , which is 8-(4-amino-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-quinolizine-3-carboxylic acid or a pharmaceutically acceptable salt thereof.