Evolution of a novel orally bioavailable series of PI3Kδ inhibitors from an inhaled lead for the treatment of respiratory disease.

Augustin Amour, Nick Barton, Anthony W.J. Cooper, Graham Inglis, Craig Jamieson, Christopher N. Luscombe, David Perez, Simon Peace, Paul Rowland, Chris Tame, Sorif Uddin, Giovanni Vitulli, Natalie Wellaway

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Abstract

A four step process of high quality modelling of existing data, deconstruction, identification of replacement cores and an innovative synthetic re-growth strategy led to the rapid discovery of a novel oral series of PI3K δ inhibitors with promising selectivity and excellent in vivo characteristics.
Original languageEnglish
Number of pages34
JournalJournal of Medicinal Chemistry
Early online date18 Jul 2016
DOIs
Publication statusE-pub ahead of print - 18 Jul 2016

Keywords

  • PI3Kδ inhibitors
  • respiratory disease
  • bioavailability
  • deconstruction
  • hinge-binding groups
  • optimisation
  • indazole core
  • physicochemical properties
  • pharmacokinetic properties

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