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Publication Abstract from PubMed

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 PI3Kalpha overexpression, gene amplification, mutations and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe how the potency of a 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 the identification of a series of 2-acetamido-5-heteroaryl imidazopyridines showing potent in vitro activity against all class I PI3Ks and attractive pharmacokinetic properties.

Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K.,Pecchi S, Ni ZJ, Han W, Smith A, Lan J, Burger M, Merritt H, Wiesmann M, Chan J, Kaufman S, Knapp MS, Janssen J, Huh K, Voliva CF Bioorg Med Chem Lett. 2013 Jun 12. pii: S0960-894X(13)00719-1. doi:, 10.1016/j.bmcl.2013.06.010. PMID:23820386^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.