標題: Design and Synthesis of Tetrahydropyridothieno[2,3-d]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency
作者: Wu, Chia-Hsien
Coumar, Mohane Selvaraj
Chu, Chang-Ying
Lin, Wen-Hsing
Chen, Yi-Rong
Chen, Chiung-Tong
Shiao, Hui-Yi
Rafi, Shaik
Wang, Sing-Yi
Hsu, Hui
Chen, Chun-Hwa
Chang, Chun-Yu
Chang, Teng-Yuan
Lien, Tzu-Wen
Fang, Ming-Yu
Yeh, Kai-Chia
Chen, Ching-Ping
Yeh, Teng-Kuang
Hsieh, Su-Huei
Hsu, John T. -A.
Liao, Chun-Chen
Chao, Yu-Sheng
Hsieh, Hsing-Pang
生物科技學系
Department of Biological Science and Technology
公開日期: 28-Oct-2010
摘要: HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.
URI: http://dx.doi.org/10.1021/jm100607r
http://hdl.handle.net/11536/32051
ISSN: 0022-2623
DOI: 10.1021/jm100607r
期刊: JOURNAL OF MEDICINAL CHEMISTRY
Volume: 53
Issue: 20
起始頁: 7316
結束頁: 7326
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