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.
引用
收藏
页码：2036 / 2042
页数：7
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