Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents

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• 作者：Ji-Wen Yuan^&dagger ; ; She-Feng Wang^&dagger ; ; Zhong-Liang Luo ; Han-Yue Qiu ; Peng-Fei Wang ; Xin Zhang ; Yong-An Yang ; Yong Yin ; Fei Zhang ; Hai-Liang Zhu ; ^{zhuhl@nju.edu.cn" class="auth_mail}
• 关键词：EGFR inhibitors ; Anti-tumor activity ; Cell migration ; Structure&ndash ; activity relationship
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 May 2014
• 年：2014
• 卷：24
• 期：10
• 页码：2324-2328
• 全文大小：1064 K

文摘

A series of compounds which contain pyrazole, thiazole and naphthalene ring (1a–7a, 1b–7b, 1c–7c, 1d–7d) were firstly synthesized and their anti-proliferative activity, EGFR inhibitory activity, cytotoxicity and inhibition to Hela cell migration were evaluated. Compound 2-(3-(3,4-dimethylphenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (7d) displayed the most potent inhibitory activity (IC₅₀ = 0.86 渭M for Hela and IC₅₀ = 0.12 渭M for EGFR). Structure–activity relationship (SAR) analysis showed that the anti-proliferative activity was affected by A-ring-substituent (–OCH₃ > –CH₃ > –H > –Br > –Cl > –F). Docking simulation of compound 7d into EGFR active site showed that naphthalene ring of 7d with LYS721 formed two p–蟺 bonds, which enhanced antitumor activity. Therefore, compound 7d may be developed as a potential antitumor agent.