Synthesis and biological evaluation of novel 1 beta-methylcarbapenems with isothiazoloethenyl side chains

Bioorg Med Chem Lett. 2003 Feb 10;13(3):463-6. doi: 10.1016/s0960-894x(02)00948-4.

Abstract

The synthesis of novel 1 beta-methylcarbapenems 1a,b bearing isothiazoloethenyl moieties at C-5 position of pyrrolidine ring and their biological evaluation are described. Both compounds showed potent and well-balanced antibacterial activity as well as high stability to DHP-I. Especially, 5-isothiazole derivative 1a exhibited excellent DHP-I stability and advanced pharmacokinetics profiles, compared to 5-isoxazole derivative 2, imipenem, and meropenem.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Carbapenems / chemical synthesis*
  • Carbapenems / pharmacokinetics
  • Carbapenems / pharmacology*
  • Half-Life
  • Indicators and Reagents
  • Meropenem
  • Mice
  • Microbial Sensitivity Tests
  • Oxidation-Reduction
  • Rats
  • Structure-Activity Relationship
  • Thienamycins / pharmacology

Substances

  • 1 beta-methylcarbapenem
  • Anti-Bacterial Agents
  • Carbapenems
  • Indicators and Reagents
  • Thienamycins
  • Meropenem