Synthesis and structure-activity relationships of novel parenteral carbapenems, CS-023 (R-115685) and related compounds containing an amidine moiety

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 s...

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Bibliographic Details
Published in:	Journal of antibiotics Vol. 56; no. 6; p. 565
Main Authors:	Kawamoto, Isao, Shimoji, Yasuo, Kanno, Osamu, Kojima, Katsuhiko, Ishikawa, Katsuya, Matsuyama, Emi, Ashida, Yuka, Shibayama, Takahiro, Fukuoka, Takashi, Ohya, Satoshi
Format:	Journal Article
Language:	English
Published:	Japan 01-06-2003
Subjects:	Animals Carbapenems - chemical synthesis Carbapenems - chemistry Carbapenems - pharmacology Humans Mice Microbial Sensitivity Tests Structure-Activity Relationship
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Summary:	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.
ISSN:	0021-8820
DOI:	10.7164/antibiotics.56.565