Design, synthesis and biological evaluation of novel thieno[3,2-d]pyrimidine derivatives possessing diaryl semicarbazone scaffolds as potent antitumor agents

作者：Liu, Zijian; Wu, Shasha; Wang, Yu; Li, Ruijuan; Wang, Jian; Wang, Lihui; Zhao, Yanfang^*; Gong, Ping

来源：European Journal of Medicinal Chemistry, 2014, 87: 782-793.

DOI：10.1016/j.ejmech.2014.10.022

• Synthesis
• Thieno[3,2-d]pyrimidine derivatives
• Diaryl semicarbazone scaffolds
• Antitumor activity

A series of novel thieno[3,2-d]pyrimidine derivatives possessing diaryl semicarbazone scaffolds were designed, synthesized and evaluated for their anticancer activity. Most compounds displayed good to excellent potency against four tested cancer cell lines as compared with GDC-0941 and sorafenib. In this study, a promising compound 36 (PI3K alpha IC50 = 0.027 mu M) was identified, which showed the most potent antitumor activities with IC50 values of 0.057 mu M, 0.039 mu M, 0.25 mu M, and 0.23 mu M against H460, HT-29, MKN-45 and MDA-MB-231 cell lines, respectively. In addition, the SAR analyses indicated that compounds with 4-morpholino group at the C-4 position of thieno[3,2-d]pyrimidine moiety exhibited superior activities than compounds bearing chain amino groups. In addition, compounds with monomethoxy group at the 3-position or dimethyl groups at the 3,5-position on the terminal phenyl ring were more active. The SAR analyses will guide us to further refine the structure of the thieno[3,2-d]pyrimidine derivatives to achieve optimum anticancer activity.

• 出版日期2014-11-24
• 单位沈阳药科大学