New quinolone antibacterial agents. Synthesis and biological activity of 7-(3,3- or 3,4-disubstituted-1-pyrrolidinyl)quinoline-3-carboxylic acids.
A series of 7-(3-amino- or 3-aminomethyl-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-o xo-3-quinolinecarboxylic acids was synthesized and tested for antibacterial activity. Unique to these quinolones was the presence of a methyl or phenyl group in the pyrrolidine ring. Although the in vitro activity of these agents was usually equal to or less than that of their unsubstituted counterparts, one quinolone, 7-[3-(aminomethyl)-3-methyl-1-pyrrolidinyl]-1-cyclopropyl-6,8-difluoro-1 ,4-dihydro-4-oxo-3-quinolinecarboxylic acid, displayed exceptional potency both in vitro and in vivo, particularly against Gram-positive organisms.
Hagen
S E
SE
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Domagala
J M
JM
Heifetz
C L
CL
Sanchez
J P
JP
Solomon
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001424:Bacterial Infections / Q000188:drug therapy; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D015363:Quinolones