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

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 NIH3T3MEN2A 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 (NIH3T3H-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.

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