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

J Antibiot (Tokyo). 2003 Jun;56(6):565-79. doi: 10.7164/antibiotics.56.565.

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.

MeSH terms

  • Animals
  • Carbapenems* / chemical synthesis
  • Carbapenems* / chemistry
  • Carbapenems* / pharmacology
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship

Substances

  • Carbapenems