Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems--I. 2-Alkoxymethyl derivatives

Bioorg Med Chem. 1997 Nov;5(11):2069-87. doi: 10.1016/s0968-0896(97)00142-9.

Abstract

The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are described. As a result of these studies, we discovered that FR27743 (19j) containing a novel 2-fluoroethoxymethyl substituent possesses a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa. Furthermore, FR27743 exhibited excellent stability against renal dehydropeptidase-I (DHP-I), good urinary recovery, and superior in vivo activity compared to that for Meropenem against several systemic infections.

MeSH terms

  • Animals
  • Carbapenems / chemical synthesis*
  • Carbapenems / chemistry
  • Carbapenems / pharmacology*
  • Dipeptidases / metabolism
  • Drug Stability
  • Male
  • Meropenem
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests
  • Pseudomonas Infections / drug therapy
  • Rats
  • Staphylococcal Infections / drug therapy
  • Thienamycins / chemical synthesis*
  • Thienamycins / chemistry
  • Thienamycins / pharmacology*
  • Urine / chemistry

Substances

  • Carbapenems
  • FR 27743
  • Thienamycins
  • Dipeptidases
  • dipeptidase
  • Meropenem