title: Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834.
abstract: We have studied an ester prodrug of a carbapenem to develop a potent orally active beta-lactam antibiotic. A variety of 1 beta-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-hydroxyethyl]-l-methyl-2-[(R)-5-oxopyrrolidin-3-yl thio]- l-carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.
authors.affiliation: Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyauchi
authors.forename: R
authors.initials: R
authors.lastname: Endo
authors.forename: M
authors.initials: M
authors.lastname: Hisaoka
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: I
authors.initials: I
authors.lastname: Kawamoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015377:Cilastatin / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007275:Injections, Intravenous; D051379:Mice; D008826:Microbial Sensitivity Tests; D011480:Protease Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D015780:Carbapenems; D011480:Protease Inhibitors; D015377:Cilastatin; C107030:CS 834