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 Ester (BMS-599626), a Selective and Orally Efficacious Inhibitor of Human Epidermal Growth Factor Receptor 1 and 2 Kinases

被引：28

作者：

Gavai, Ashvinikumar V. ^{[1
]}

Fink, Brian E. ^{[1
]}

Fairfax, David J. ^{[2
]}

Martin, Gregory S. ^{[2
]}

Rossiter, Lana M. ^{[2
]}

Holst, Christian L. ^{[2
]}

Kim, Soong-Hoon ^{[1
]}

Leavitt, Kenneth J. ^{[1
]}

Mastalerz, Harold ^{[1
]}

Han, Wen-Ching ^{[1
]}

Norris, Derek ^{[1
]}

Goyal, Bindu ^{[1
]}

Swaminathan, Shankar ^{[1
]}

Patel, Bharat ^{[1
]}

Mathur, Arvind ^{[1
]}

Vyas, Dolatrai M. ^{[1
]}

Tokarski, John S. ^{[1
]}

Yu, Chiang ^{[1
]}

Oppenheimer, Simone ^{[1
]}

Zhang, Hongjian ^{[1
]}

Marathe, Punit ^{[1
]}

Fargnoli, Joseph ^{[1
]}

Lee, Francis Y. ^{[1
]}

Wong, Tai W. ^{[1
]}

Vite, Gregory D. ^{[1
]}

机构：

[1] Bristol Myers Squibb Res & Dev, Princeton, NJ 08543 USA

[2] Albany Mol Res, Albany, NY 12212 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 21期

关键词：

EGFR; HER-2/NEU; DESIGN;

D O I：

10.1021/jm9010065

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：6527 / 6530

页数：4

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