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.
Cuihua Wang  1 ,  Sofia Barluenga ,  Girish K Koripelly ,  Jean-Gonzague Fontaine ,  Ruihong Chen ,  Jin-Chen Yu ,  Xiaodong Shen ,  John C Chabala ,  James V Heck ,  Allan Rubenstein ,  Nicolas Winssinger
Affiliations
  • 1. Institute de Science et d'Ingénierie Supramoleculaires, Université de Strasbourg, Strasbourg, France.
PMID: 19410458 DOI: 10.1016/j.bmcl.2009.04.030
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.