Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway

  • Bioorg Med Chem Lett. 2012 Sep 1;22(17):5445-50. doi: 10.1016/j.bmcl.2012.07.042.
Ian Bruce  1 ,  Mohammed Akhlaq ,  Graham C Bloomfield ,  Emma Budd ,  Brian Cox ,  Bernard Cuenoud ,  Peter Finan ,  Peter Gedeck ,  Julia Hatto ,  Judy F Hayler ,  Denise Head ,  Thomas Keller ,  Louise Kirman ,  Catherine Leblanc ,  Darren Le Grand ,  Clive McCarthy ,  Desmond O'Connor ,  Charles Owen ,  Mrinalini S Oza ,  Gaynor Pilgrim ,  Nicola E Press ,  Lilya Sviridenko ,  Lewis Whitehead
Affiliations
  • 1. Novartis Institutes for Biomedical Research, Respiratory Disease Area, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. [email protected]
PMID: 22863202 DOI: 10.1016/j.bmcl.2012.07.042
Abstract

Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide Alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein Kinases and other members of the PI3K superfamily including mTOR and DNA-PK.

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