Design, Synthesis and Anticancer Activity of 4-Morpholinothieno[3,2-d]pyrimidine Derivatives Bearing Arylmethylene Hydrazine Moiety

Wufu Zhu; Xin Zhai; Qiangqiang Fu; Fei Guo; Mei Bai; Jianqiang Wang; Haiyan Wang; Ping Gong

doi:10.1248/cpb.c12-00342

Regular Articles

Design, Synthesis and Anticancer Activity of 4-Morpholinothieno[3,2-d]pyrimidine Derivatives Bearing Arylmethylene Hydrazine Moiety

Wufu Zhu, Xin Zhai, Qiangqiang Fu, Fei Guo, Mei Bai, Jianqiang Wang, Haiyan Wang, Ping Gong

Author information

Wufu Zhu
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University
Xin Zhai
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University
Qiangqiang Fu
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University
Fei Guo
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University
Mei Bai
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University
Jianqiang Wang
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University
Haiyan Wang
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University
Ping Gong
Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University

Keywords: 4-morpholinothieno[3,2-d]pyrimidine, arylmethylene hydrazine, synthesis, anticancer activity

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Supplementary material

2012 Volume 60 Issue 8 Pages 1037-1045

DOI https://doi.org/10.1248/cpb.c12-00342

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Abstract

Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a–f, 13a–k and 15a–h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC₅₀ values of 0.003 µM, 0.42 µM and 0.74 µM, which was 1.6- to 290-fold more potent than GDC-0941.

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