新型5,6,7,8-四氢苯并噻吩并嘧啶酮衍生物的合成与抗肿瘤活性研究
收稿日期: 2014-10-24
修回日期: 2015-12-15
网络出版日期: 2015-01-05
基金资助
湖北自然科学基金(No.2011CDC006)、湖北省2011协同创新中心基金(No.2011JH-2014CXTT07)和湖北医药学院优秀中青年科技创新团队研究(Nos.2011CXX03,2009QDJ15,2014XKJSXJ06)资助项目.
Synthesis and Antitumor Activity of Some Novel 5,6,7,8-Tetrahydro- benzo-thieno[2,3-d]pyrimidin-4(3H)-one Derivatives
Received date: 2014-10-24
Revised date: 2015-12-15
Online published: 2015-01-05
Supported by
Project supported by the Natural Science Foundation of Hubei Province (No.2011CDC006), the Fund of Hubei 2011 Cooperative Innovation Center (No.2011JH-2014CXTT07) and the Science and Technology Innovation team Project of Hubei University of Medicine (Nos.2011CXX03, 2009QDJ15, 2014XKJSXJ06).
应用5,6,7,8-四氢苯并噻吩膦亚胺(2)与烷基异氰酸酯的氮杂Wittig反应生成碳二亚胺2, 在不同的条件下, 2分别与不同的亲核试剂反应, 有效地合成了不同取代的新型稠合噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物. 所得化合物的结构由1H NMR, IR, MS和元素分析所确证. 初步的体外抗肿瘤活性测试, 结果显示目标化合物具有抑制肿瘤细胞的生长, 其中5d对口腔肿瘤细胞KB2IC50值为19.0 μmol/L, 表现出潜在的抗肿瘤活性.
关键词： 氮杂Wittig反应; 噻吩并嘧啶酮; 合成; 抗肿瘤活性
王红梅 , 郭树兵 , 胡扬根 , 曾小华 , 杨光义 . 新型5,6,7,8-四氢苯并噻吩并嘧啶酮衍生物的合成与抗肿瘤活性研究[J]. 有机化学, 2015 , 35(5) : 1075 -1080 . DOI: 10.6023/cjoc201410035
The aza-Wittig reaction of iminophosphorane 2 with alkyl isocyanates gave carbodiimides 3, which were allowed to react with various nucleophilic reagents under mild condition in satisfactory yields to prepare a novel series of 5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one derivatives. The structures of these compounds were confirmed by 1H NMR, IR, MS and elemental analysis. The in vitro antitumor activities of compounds were analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide (MTT) standard method, 5d stood out as the most potent showing an IC50 of 19.0 μmol/L against human tumor cell lines (KB).
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