Discovery of novel 5-alkynyl-4-anilinopyrimidines as potent, orally active dual inhibitors of EGFR and Her-2 tyrosine kinases

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• 作者：Naoyuki Suzuki ; ^{naoyuki.suzuki@shionogi.co.jp} ; Takeshi Shiota ; Fumihiko Watanabe ; Norihiro Haga ; Takami Murashi ; Takafumi Ohara ; Kenji Matsuo ; Naoki Omori ; Hiroshi Yari ; Keiji Dohi ; Makiko Inoue ; Motofumi Iguchi ; Jyunko Sentou ; Tooru Wada
• 关键词：Kinase inhibitor ; EGFR ; Her-2 ; BT474 ; N87 ; Pyrimidine ; Antitumor efficacy
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 January, 2012
• 年：2012
• 卷：22
• 期：1
• 页码：456-460
• 全文大小：624 K

文摘

5-Alkenyl or 5-alkynyl-4-anilinopyrimidines were prepared and evaluated for in vitro inhibition of EGFR/Her-2 kinase activity and the growth of tumor cell lines (BT474 and N87). Several of these compounds inhibited the growth of BT474 and N87 at concentrations below 200 nM. Structure-activity relationship studies revealed a critical role for the 5-alkynyl moieties. The representative compound 19 exhibited significant antitumor potency in a mouse xenograft model.