Discovery and Preclinical Evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic Acid, (3S)-3-Morpholinylmethyl Este

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• 作者：Ashvinikumar V. Gavai ; Brian E. Fink ; David J. Fairfax ; Gregory S. Martin ; Lana M. Rossiter ; Christian L. Holst ; Soong-Hoon Kim ; Kenneth J. Leavitt ; Harold Mastalerz ; Wen-Ching Han ; Derek Norris ; Bind
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：November 12, 2009
• 年：2009
• 卷：52
• 期：21
• 页码：6527-6530
• 全文大小：732K
• 年卷期：v.52,no.21(November 12, 2009)
• ISSN：1520-4804

文摘

Structure−activity relationships in a series of 4-[1H-indazol-5-ylamino]pyrrolo[2,1-f][1,2,4]triazine-6-carbamates identified dual human epidermal growth factor receptor (HER)1/HER2 kinase inhibitors with excellent biochemical potency and kinase selectivity. On the basis of its favorable pharmacokinetic profile and robust in vivo activity in HER1 and HER2 driven tumor models, 13 (BMS-599626) was selected as a clinical candidate for treatment of solid tumors.