Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474. Issue 20 (15th October 2017)

• Record Type: Journal Article
• Authors: Gamage, Swarna A.; Giddens, Anna C.; Tsang, Kit Y.; Flanagan, Jack U.; Kendall, Jackie D.; Lee, Woo-Jeong; Baguley, Bruce C.; Buchanan, Christina M.; Jamieson, Stephen M.F.; Shepherd, Peter R.; Denny, William A.; Rewcastle, Gordon W.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 20(2017)
• Page Start: 5859
• Page End: 5874
• Publication Date: 2017-10-15
• Subjects: Phosphatidylinositol 3-kinase -- PI3K -- p110α -- ZSTK474; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.09.025
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 derivative17 from being evaluated in vivo, but the clear activity of this compound demonstrated that this class of PI3K inhibitor shows great promise.