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ID: ALA1139977

Journal: Bioorg Med Chem Lett

Title: Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones.

Authors: Rizzi E, Cassinelli G, Dallavalle S, Lanzi C, Cincinelli R, Nannei R, Cuccuru G, Zunino F.

Abstract: A novel series of 3-arylureidobenzylidene-indolin-2-ones was synthesized and their inhibitory activity against Ret tyrosine kinase investigated in comparison with the Ret inhibitor RPI-1 as a reference compound for this series. A few compounds were able to revert the RETC634R oncogene-transformed morphologic phenotype of NIH3T3(MEN2A) cells and showed a selective antiproliferative activity against these cells as compared to parental NIH3T3 cells or NIH3T3 cells transformed with a non-tyrosine kinase oncogene (NIH3T3(H-RAS)). Inhibition of Ret enzyme activity by effective derivatives was confirmed in a kinase assay. Structure-activity relationship indicated a favourable activity for 5,6-dimethoxyindolinone derivatives with H, OH, or OMe in the para position of the distal aryl ring.

CiteXplore: 17499504

DOI: 10.1016/j.bmcl.2007.04.091