Design, synthesis and evaluation of 2-phenylisothiazolidin-3-one-1,1-dioxides as a new class of human protein kinase CK2 inhibitors

摘要

The synthesis and in vitro evaluation of 40 new 2-phenylisothiazolidin-3-one-1,1-dioxide derivatives are described. The optimization based on biological screening data and molecular modeling resulted in a 10-fold increase in inhibitory activity compared with previously reported inhibitors of this class and led to the identification of 3-{[2-chloro-4-(1,1-dioxido-3- oxoisothiazolidin-2-yl)benzoyl]amino}benzoic acid, a potent inhibitor of human protein kinase CK2 (IC50 = 1.5 mu M).