2-phenylisothiazolidin-3-one-1,1-dioxides

We have synthesized 40 new 2-phenylisothiazolidin-3-one-1,1-dioxide derivatives. 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 μM) (Fig. 1). 

Figure 1. The binding mode of 2-phenylisothiazolidin-3-one-1,1-dioxide inhibitor obtained with molecular docking. Intermolecular hydrogen bonds are indicated with dotted lines.

• Design, synthesis and evaluation of 2-phenylisothiazolidin-3-one-1,1-dioxides as a new class of human protein kinase CK2 inhibitors. Chekanov MO, Ostrynska OV, Synyugin AR, Bdzhola VG, Yarmoluk SM. J Enzyme Inhib Med Chem. 2014, 29(3):338-343.