title: Synthesis and structure-activity relationships of novel parenteral carbapenems, CS-023 (R-115685) and related compounds containing an amidine moiety.
abstract: In order to design a new parenteral 1beta-methylcarbapenem antibiotic which has a broad antibacterial spectrum and improved plasma half-life, a series of 1beta-methylcarbapenems with 5-substituted pyrrolidine-3-ylthio groups including an amidine moiety at the C-2 position have been synthesized and structure-activity relationships were investigated. Among those carbapenem derivatives, CS-023 (R-115685) showed a broad spectrum and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. This compound also showed sufficient dehydropeptidase-I (DHP-I) stability and high urinary recovery in animals after subcutaneous administration without cilastatin, a DHP-I inhibitor. Based on these characteristics, CS-023 was selected for further study.
authors.affiliation: Research Laboratories, Sankyo Co., Ltd. 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kawamoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shimoji
authors.forename: Osamu
authors.initials: O
authors.lastname: Kanno
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kojima
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Emi
authors.initials: E
authors.lastname: Matsuyama
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ashida
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shibayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuoka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohya
mesh_terms: D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D015780:Carbapenems