PI3 Kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation.  The PI3 Kinase pathway is often de-regulated in cancer through PI3K alpha overexpression, gene amplification, mutation and PTEN phosphatase deletion. PI3K inhibition represents therefore an attractive therapeutic modality for cancer treatment.  Herein we describe how the potency of a 2-acetamido benzothiazole fragment hit was quickly improved based on structural information and how this early chemotype was further optimized through scaffold hopping.  This effort led to a series of 2-acetamido-6-heterocyclyl imidazopyridines showing potent in vitro activity against class I PI3Ks.

Structure guided optimization of a fragment hit to a series of imidazopyridine inhibitors of PI3K

243rd National Meeting (2012)

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