Imidazo[2,1-b]thiazolylmethylene- and indolylmethylene-2-indolinones: a new class of cyclin-dependent kinase inhibitors. Design, synthesis, and CDK1/cyclin B inhibition

Compounds containing a 2-indolinone moiety linked to imidazothiazole and in dole fragments were studied as cyclin-dependent kinase inhibitors. The acti vity of all the new derivatives was tested in vitro against CDK1/cyclinB an d the selectivity towards two other kinases was determined for the most pro mising compounds. The binding mode of one representative compound was inves tigated by means of a three-dimensional model of the inhibitor-CDK1 complex . The work allowed us to identify (2-chloroindolyl)methylene-2-indolinone a s a new lead of a class of CDK1/cyclinB inhibitors, whose potency can be im proved by the introduction of suitable variations on the basic molecular sk eleton.