Synthesis and properties of 2-(naphthosultamyl)methyl-carbapenems with potent anti-MRSA activity: discovery of L-786,392

Bioorg Med Chem Lett. 1999 Mar 8;9(5):679-84. doi: 10.1016/s0960-894x(99)00071-2.

Abstract

A series of 1beta-methyl-2-(naphthosultamyl)methyl-carbapenems bearing dicationic groups on the naphthosultamyl moiety was prepared and evaluated for activity against resistant gram-positive bacteria. Based on a combination of excellent in vitro antibacterial activity, acceptable mouse acute toxicity, and a desirable fragmentation pattern on beta-lactam ring opening, the analog 2g (L-786,392) was selected for extended evaluation.

MeSH terms

  • Animals
  • Carbapenems / chemical synthesis*
  • Carbapenems / chemistry
  • Carbapenems / pharmacology
  • Carbapenems / toxicity
  • Drug Resistance, Microbial
  • Gram-Positive Bacteria / drug effects*
  • Humans
  • Lactams / chemistry
  • Lactams / pharmacokinetics
  • Lactams / pharmacology*
  • Mice
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacokinetics
  • Thiazoles / pharmacology*

Substances

  • Carbapenems
  • Lactams
  • Thiazoles
  • L 786392