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ID: ALA2203257

Journal: Bioorg Med Chem Lett

Title: Discovery of 5-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-N-(tert-butyl)pyridine-3-sulfonamide (CZC24758), as a potent, orally bioavailable and selective inhibitor of PI3K for the treatment of inflammatory disease.

Authors: Sunose M, Bell K, Ellard K, Bergamini G, Neubauer G, Werner T, Ramsden N.

Abstract: Herein, we disclose the discovery of a series of 7-substituted triazolopyridines which culminated in the identification of 14 (CZC24758), a potent, orally bioavailable small-molecule inhibitor of PI3Kγ, an attractive drug target for inflammatory and autoimmune disorders. Compound 14 has excellent selectivity across the kinome, demonstrates good potency in cell based assays and furthermore exhibits in vivo efficacy in a collagen induced arthritis model in mouse after oral dosing.

CiteXplore: 22726925

DOI: 10.1016/j.bmcl.2012.05.090