2. Academic Validation
  3. Combination of 4-anilinoquinazoline, arylurea and tertiary amine moiety to discover novel anticancer agents

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

  • Bioorg Med Chem. 2016 Jan 15;24(2):179-90. doi: 10.1016/j.bmc.2015.12.001.
Sai-Jie Zuo 1,  Sai Zhang 2,  Shuai Mao 1,  Xiao-Xiao Xie 1,  Xue Xiao 2,  Min-Hnag Xin 1,  Wei Xuan 1,  Yuan-Yuan He 1,  Yong-Xiao Cao 2,  San-Qi Zhang 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
  • 2 Department of Pharmacology, School of Basic Medical Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: sqzhang@mail.xjtu.edu.cn.
PMID: 26706113 DOI: 10.1016/j.bmc.2015.12.001
Abstract

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.

Keywords

Anticancer agent; Diaryl urea; EGFR-TK inhibitor; Gefitinib; Tertiary amine.

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