Evolution of a Novel, Orally Bioavailable Series of PI3Kδ Inhibitors from an Inhaled Lead for the Treatment of Respiratory Disease

  • J Med Chem. 2016 Aug 11;59(15):7239-51. doi: 10.1021/acs.jmedchem.6b00799.
Augustin Amour  1 ,  Nick Barton  1 ,  Anthony W J Cooper  1 ,  Graham Inglis  1 ,  Craig Jamieson  2 ,  Christopher N Luscombe  1 ,  Josie Morrell  1 ,  Simon Peace  1 ,  David Perez  1 ,  Paul Rowland  1 ,  Christopher J Tame  1 ,  Sorif Uddin  1 ,  Giovanni Vitulli  1 ,  Natalie Wellaway  1
Affiliations
  • 1. GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
  • 2. Department of Pure and Applied Chemistry, University of Strathclyde , 295 Cathedral Street, Glasgow G1 1XL, U.K.
PMID: 27429068 DOI: 10.1021/acs.jmedchem.6b00799
Abstract

A four-step process of high-quality modeling of existing data, deconstruction, identification of replacement cores, and an innovative synthetic regrowth strategy led to the rapid discovery of a novel oral series of PI3Kδ inhibitors with promising selectivity and excellent in vivo characteristics.

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