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

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• 作者：Eleonora Rizzi ; Giuliana Cassinelli ; Sabrina Dallavalle ; Cinzia Lanzi ; Raffaella Cincinelli ; Raffaella Nannei ; Giuditta Cuccuru ; Franco Zunino
• 关键词：RET ; Protein kinase ; Antitumour ; Thyroid cancer ; Indolinone ; Synthesis
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 July 2007
• 卷：17
• 期：14
• 页码：3962-3968
• 文件大小：287 K

摘要

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.