Discovery, SAR, synthesis, pharmacokinetic and biochemical characterization of A-192411: a novel fungicidal lipopeptide-(I)

Bioorg Med Chem Lett. 2003 Feb 10;13(3):489-93. doi: 10.1016/s0960-894x(02)00978-2.

Abstract

The echinocandin class of cyclic lipopeptides has been simplified to discover potent antifungal compounds. Namely A-192411 shows good in vitro activity against common pathogenic yeasts and has an acceptable safety window in vivo. Discovery, limited SAR, synthesis, biochemical and pharmaco-dynamic profiles of A-192411 are presented.

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / pharmacology*
  • Area Under Curve
  • Candida / drug effects
  • Candida / metabolism
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Chemical Phenomena
  • Chemistry, Physical
  • Dogs
  • Drug Design
  • Fungi / drug effects
  • Fungi / metabolism*
  • Glucans / metabolism
  • Haplorhini
  • Mice
  • Microbial Sensitivity Tests
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacokinetics
  • Oligopeptides / pharmacology*
  • RNA, Fungal / biosynthesis
  • Rats
  • Structure-Activity Relationship

Substances

  • A-192411
  • Antifungal Agents
  • Glucans
  • Oligopeptides
  • RNA, Fungal