Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone

  • Bioorg Med Chem Lett. 2008 Dec 1;18(23):6273-8. doi: 10.1016/j.bmcl.2008.09.081.
Pei-Pei Kung  1 ,  Lee Funk ,  Jerry Meng ,  Michael Collins ,  Joe Zhongxiang Zhou ,  M Catherine Johnson ,  Anne Ekker ,  Jeff Wang ,  Pramod Mehta ,  Min-Jean Yin ,  Caroline Rodgers ,  Jay F Davies 2nd ,  Eileen Bayman ,  Tod Smeal ,  Karen A Maegley ,  Michael R Gehring
Affiliations
  • 1. Pfizer Global Research and Development, La Jolla Laboratories, 10770, Science Center Dr., San Diego, CA 92121, USA. [email protected]
PMID: 18929486 DOI: 10.1016/j.bmcl.2008.09.081
Abstract

Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a HSP90 competitive binding assay. A class of novel and potent small molecule HSP90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human Cancer cell lines in vitro, with IC(50) values averaging 20 nM.