2-PYRIDONE ANTIMICROBIAL COMPOSITIONS
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.