Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474

Publication date: Available online 20 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Swarna A. Gamage, Anna C. Giddens, Kit Y. Tsang, Jack U. Flanagan, Jackie D. Kendall, Woo-Jeong Lee, Bruce C. Baguley, Christina M. Buchanan, Stephen M.F. Jamieson, Peter R. Shepherd, William A. Denny, Gordon W. Rewcastle
Replacement of one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 (1) with sulfonamide containing substituents produced a new class of active and potent PI3Kα inhibitors. Solubility issues prevented all but the 6-amino derivative 17 from being evaluated in vivo, but the clear activity of this compound demonstrated that this class of PI3K inhibitor shows great promise.

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