Compounds containing a 2-indolinone moiety linked to imidazothiazole and indole fragments were studied as cyclin-dependent kinase inhibitors. The activity of all the new derivatives was tested in vitro against CDK1/cyclinB and the selectivity towards two other kinases was determined for the most promising compounds. The binding mode of one representative compound was investigated by means of a three-dimensional model of the inhibitor-CDK1 complex. The work allowed us to identify (2-chloroindolyl)methylene-2-indolinone as a new lead of a class of CDK1/cyclinB inhibitors, whose potency can be improved by the introduction of suitable variations on the basic molecular skeleton.