Bioorganic & Medicinal Chemistry Letters 2012-09-01

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

Ian Bruce, 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

Index: Bioorg. Med. Chem. Lett. 22(17) , 5445-50, (2012)

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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.Copyright © 2012 Elsevier Ltd. All rights reserved.