Microwave synthesis of new 3-(3-aminopropyl)-5-arylidene-2-thioxo-1,3-thiazolidine-4-ones as potential Ser/Thr protein kinase inhibitors
Abstract
The synthesis of a series of new 3-(3-aminopropyl)-5-arylidene-2-thioxo-1,3-thiazolidine-4-ones hydrochlorides was reported. The key step of this synthetic approach involved a "one-pot two-step" protocol under microwave dielectric heating with good stereocontrol of the Knoevenagel condensation for all these new 5-arylidene rhodanines. The 18 new compounds were evaluated for their in vitro cell proliferation inhibition and also for their kinase inhibitory potencies against seven protein kinases. Two compounds (7f and 7r) were identified as potential protein kinase inhibitors. New (5Z) 3-(3-aminopropyl)-5-arylidene rhodanine derivatives 7a-r were synthesized in four steps with overall yields ranging from 7 to 68 % and tested against seven protein kinases (HsCDK5-p25, GSK3 alpha/beta, SsCK1 delta/epsilon, HsHaspin, HsRIPK3, HsPIM1 and Aurora B).