Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5]

Bioorg Med Chem Lett. 2006 Jan 1;16(1):186-90. doi: 10.1016/j.bmcl.2005.09.031. Epub 2005 Nov 2.

Abstract

As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies.

MeSH terms

  • Alcohols
  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Aspergillosis / drug therapy
  • Candidiasis / drug therapy
  • Chemistry, Pharmaceutical / methods*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Evaluation, Preclinical
  • Haplorhini
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Mice
  • Models, Chemical
  • Time Factors
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry*
  • Triazoles / pharmacokinetics
  • Triazoles / pharmacology*

Substances

  • Alcohols
  • Antifungal Agents
  • Immunosuppressive Agents
  • SCH 51048
  • Triazoles
  • posaconazole