New C-5 substituted pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases

被引：42

作者：

Mastalerz, Harold

Chang, Ming

Chen, Ping

Dextraze, Pierre

Fink, Brian E.

Gavai, Ashvinikumar

Goyal, Bindu

Han, Wen-Ching

Johnson, Walter

Langley, David

Lee, Francis Y.

Marathe, Punit

Mathur, Arvind

Oppenheimer, Simone

Ruediger, Edward

Tarrant, James

Tokarski, John S.

Vite, Gregory D.

Vyas, Dolatrai M.

Wong, Henry

Wong, Tai W.

Zhang, Hongjian

Zhang, Guifen

机构：

[1] Dept Oncol Chem, Wallingford, CT 06492 USA

[2] Dept Discovery Biol, Wallingford, CT 06492 USA

[3] Dept Pharmaceut Candidate Optimizat, Wallingford, CT 06492 USA

[4] Dept Comp Aided Drug Design, Wallingford, CT 06492 USA

[5] Dept Chem Synth, Wallingford, CT 06492 USA

[6] Bristol Myers Squibb Pharmaceut Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 07期

关键词：

EGFR; HER2; receptor tyrosine kinase inhibitor; pyrrolotriazine;

D O I：

10.1016/j.bmcl.2007.01.002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel C-5 substituted pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.

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页码：2036 / 2042

页数：7

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