Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains.
The synthesis and antibacterial activity of 1beta-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied. Two types of new carbapenem derivatives have been synthesized. These 1beta-methylcarbapenems, one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio-4-+ ++ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-yl carbonyl)pyrrolidin-4-ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.
Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
K
K
Ishikawa
K
K
Kojima
M
M
Miyauchi
R
R
Endo
H
H
Yasuda
I
I
Kawamoto
D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D015780:Carbapenems