Synthesis and Evaluation of New Isatin-Aminorhodanine Hybrids as Pim1 and Clk1 Kinase Inhibitors

Abstract

A series of new hybrid isatin-aminorhodanine molecules was prepared by microwave activation under mild conditions. Unexpected condensation of isatin derivatives at C-5 position of aminorhodanine was highlighted and confirmed by NMR and X-ray analyses. The inhibitory activity of these compounds was evaluated towards eight protein kinases, CDK's-2,-5,-9; PIM-1, CLK-1, Haspin, GSK3β and DYRK1A, whose signaling pathway dysregulation is associated to multifactorial diseases such as cancer, inflammatory, cardiovascular, and neurodegenerative diseases. Compound 3l bearing a bromo substituent has shown a potent and selective Pim1 kinase inhibitor activity. © 2019 Elsevier B.V.