Synthesis of pochoxime prodrugs as potent HSP90 inhibitors

Bioorg Med Chem Lett. 2009 Jul 15;19(14):3836-40. doi: 10.1016/j.bmcl.2009.04.030. Epub 2009 Apr 17.

Abstract

Pochoximes are potent inhibitors of heat shock protein 90 (HSP90) based on the radicicol pharmacophores. Herein we present a pharmacokinetics and pharmacodynamics evaluation of this compound series as well as a phosphate prodrug strategy to facilitate formulation and improve oral bioavailability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Macrolides / chemistry
  • Mice
  • Mice, Inbred ICR
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / pharmacokinetics
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Macrolides
  • Prodrugs
  • monorden