2. Academic Validation
  3. N-aryl-benzimidazolones as novel small molecule HSP90 inhibitors

N-aryl-benzimidazolones as novel small molecule HSP90 inhibitors

  • Bioorg Med Chem Lett. 2010 Dec 15;20(24):7503-6. doi: 10.1016/j.bmcl.2010.10.010.
Milan Bruncko 1,  Stephen K Tahir,  Xiaohong Song,  Jun Chen,  Hong Ding,  Jeffrey R Huth,  Sha Jin,  Russell A Judge,  David J Madar,  Chang H Park,  Cheol-Min Park,  Andrew M Petros,  Christin Tse,  Saul H Rosenberg,  Steven W Elmore
Affiliations

Affiliation

  • 1 Cancer Research, Global Pharmaceutical R&D, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. milan.bruncko@abbott.com
PMID: 21106457 DOI: 10.1016/j.bmcl.2010.10.010
Abstract

We describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors (9) targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around X-ray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATP-ase inhibition and cellular client protein degradation.

Figures