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.
Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones / E. Rizzi, G. Cassinelli, S. Dallavalle, C. Lanzi, R. Cincinelli, R. Nannei, G. Cucurru, F. Zunino. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 17:14(2007 Jul 15), pp. 3962-3968.
|Titolo:||Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones|
|Parole Chiave:||Antitumour; Indolinone; Protein kinase; RET; Synthesis; Thyroid cancer|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
Settore CHIM/08 - Chimica Farmaceutica
|Data di pubblicazione:||15-lug-2007|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bmcl.2007.04.091|
|Appare nelle tipologie:||01 - Articolo su periodico|