3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone

Bioorg Med Chem Lett. 2005 Dec 1;15(23):5197-201. doi: 10.1016/j.bmcl.2005.08.091. Epub 2005 Oct 5.

Abstract

Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction.

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology
  • Crystallography, X-Ray
  • Drug Design
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Molecular Structure
  • Oxamic Acid / chemistry
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology

Substances

  • Amides
  • HSP90 Heat-Shock Proteins
  • Pyrazoles
  • Oxamic Acid

Associated data

  • PDB/2BYH
  • PDB/2BYI