Portal de Periódicos da CAPES

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

2019; Elsevier BV; Volume: 27; Issue: 8 Linguagem: Inglês

10.1016/j.bmc.2019.02.050

1464-3391

Anna C. Giddens, Swarna A. Gamage, Jackie D. Kendall, Woo Jung Lee, Bruce C. Baguley, Christina M. Buchanan, Stephen M. F. Jamieson, James M. Dickson, Peter R. Shepherd, William A. Denny, Gordon W. Rewcastle,

Chronic Lymphocytic Leukemia Research

Replacing one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 with a variety of sulfonamide-linked solubilizing substituents produced a new class of active and potent PI3Kα inhibitors, with several derivatives demonstrating high PI3Kα enzyme potency and good cellular potency in two human derived cell lines. The overall results suggest a preference for linear and somewhat flexible solubilizing functions. From this series, compound 16, also known as SN32976, was selected for advanced preclinical evaluation.