Combination of 4-anilinoquinazoline, arylurea and tertiary amine moiety to discover novel anticancer agents

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• 作者：Sai-Jie Zuo^a ; Sai Zhang^b ; Shuai Mao^a ; Xiao-Xiao Xie^a ; Xue Xiao^b ; Min-Hnag Xin^a ; Wei Xuan^a ; Yuan-Yuan He^a ; Yong-Xiao Cao^b ; San-Qi Zhang^a ; ^{sqzhang@mail.xjtu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Gefitinib ; Diaryl urea ; Tertiary amine ; EGFR-TK inhibitor ; Anticancer agent
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：24
• 期：2
• 页码：179-190
• 全文大小：1496 K

文摘

In present study, 4-anilinoquinazolines scaffold, arylurea and tertiary amine moiety were combined to design, synthesize gefitinib analogs and discover novel anticancer agents. A series of 4-anilinoquinazoline derivatives (1, 2, 3 and 4) bearing arylurea and tertiary amine moiety at its 6-position were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against A431 cell and A549 cell. The SAR of the title compounds was discussed. The compounds 2d, 2i and 2j with potent antiproliferative activities were evaluated their inhibitory activity against EGFR-TK. Compound 2j displayed potent inhibitory activity against EGFR-TK. In addition, compound 2j, at 50 mg/kg, can completely inhibit cancer growth in established nude mouse A549 xenograft model in vivo. These results suggest that the 4-anilinoquinazoline derivatives bearing diarylurea and tertiary amino moiety at its 6-position can serve as anticancer agents and EGFR inhibitors.