5-Benzylidene-hydantoins as new EGFR inhibitors with antiproliferative activity

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• 作者：Caterina Carmi ; Andrea Cavazzoni ; Valentina Zuliani ; Alessio Lodola ; Fabrizio Bordi ; Pier Vincenzo Plazzi ; Roberta R. Alfieri ; Pier Giorgio Petronini and Marco Mor
• 关键词：Hydantoin ; EGFR ; Tyrosine kinase ; Antiproliferative activity ; Antitumor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2006
• 出版时间：1 August 2006
• 年：2006
• 卷：16
• 期：15
• 页码：4021-4025
• 全文大小：217 K

文摘

A series of 1,5-disubstituted hydantoins, whose structure was designed to interact at the ATP-binding site of EGFR, was synthesized and evaluated for inhibition of EGFR kinase activity and antiproliferative action. Some of these compounds, characterized by a 1-phenethyl and a 5-(E)-benzylidene substituent, inhibited EGFR autophosphorylation and polyGAT phosphorylation, and also inhibited the growth and proliferation of human A431 cells, which overexpress EGFR. These compounds can therefore be regarded as examples of a new scaffold for tyrosine kinase inhibitors.