Conformationally-restricted cyclic sulfones as potent and selective mTOR kinase inhibitors

  • Bioorg Med Chem Lett. 2012 Aug 1;22(15):5114-7. doi: 10.1016/j.bmcl.2012.05.104.
Kevin K-C Liu  1 ,  Simon Bailey ,  Dac M Dinh ,  Hieu Lam ,  Chunze Li ,  Peter A Wells ,  Min-Jean Yin ,  Aihua Zou
Affiliations
  • 1. Pfizer Global Research and Development, Chemistry Department, La Jolla, CA 92120, USA. [email protected]
PMID: 22765900 DOI: 10.1016/j.bmcl.2012.05.104
Abstract

Novel conformationally-restricted mTOR kinase inhibitors with cyclic sulfone scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the mTOR potency and selectivity against class I PI3Kα kinase. PF-05139962 was identified with excellent mTOR biochemical inhibition, cellular potency, kinase selectivity and in vitro ADME properties.

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