| 第 41 卷第 2 期 |  | Vol. 41 No. 2 | | 2011 年 4 月 | Apr 2011 |
|
所属栏目：医药及中间体
4，5-二氢-1H-硫色烯［4，3-d］嘧啶类化合物合成及抗肿瘤细胞增殖活性研究 |
| 郭德祥1，赵晓妍2，何 影1，胡 春1，宫 平1*
（1. 沈阳药科大学 制药工程学院，辽宁 沈阳110016；2. 河北省衡水市药品检验所，河北 衡水 053000） |
| 摘 要：以苯硫酚为起始原料经Michael加成，环合得到硫色满酮，再利用3组分（醛、酮、氨基脒）反应合成了4，5-二氢-1H-硫色烯［4，3-d］嘧啶类目标化合物，所合成的5个目标化合物未见文献报道，其结构经核磁共振氢谱和质谱确证。采用MTT法，以吉非替尼（gefitinib）为阳性对照药，测定了目标化合物对肺腺癌A549细胞和非小细胞肺癌H460细胞的体外抗肿瘤增殖活性。化合物GDX1和GDX2对A549和H460的抑制活性较强，其IC50值分别为0.77、0.67、4.38、3.78 μmol／L。实验表明4，5-二氢-1H-硫色烯［4，3-d］嘧啶类化合物是一类具有新型骨架结构的抗肿瘤化合物，值得进一步研究。 |
| 关键词：杂环；4，5-二氢-1H-嘧啶并硫色烯；抗肿瘤增殖活性 |
| 中图分类号：TQ254.1 文献标识码：A 文章编号：1009-9212（2011）02-0032-04 |
|
| Synthesis and Antiproliferative Activity of Novel 4，5-Dihydro-1H-thiochromeno［4，3-d］pyrimidine Derivatives |
| GUO De-xiang1，ZHAO Xiao-yan2，HE Ying1，HU Chun1，GONG Ping1*
（1. School of Pharmaceutical Engineering，Shenyang Pharmaceutical University，Shenyang 110016，China；2. Hengshui Institute for Drug Control，Hengshui 053000，China） |
| Abstract：Five of novel 4，5-dihydro-1H-thiochrochromeno ［4，3-d］ pyrimidine derivatives were synthesized from single step reaction under aldehyde，ketone and aminoamidines，in which the ketones belonged to thiochromanone derivatives prepared by Michael addition and cyclization from thiophenols as the start materials. The target compounds are characterized by NMR and MS. The antiproliferative activities of the target compounds have been evaluated in vitro against two human cancer cell lines including A549（human alveolar adenocarcinoma cell） and H460（human lung cancer） by MTT assay with gefitinib，a standard anticancer drug，as the positive control. The target compounds GDX1 and GDX2 showed good activity in vitro against A549 and H460 cells in vitro，with the half maximal inhibitory concentration of 0.77，0.67 and 4.38，3.78 μmol／L，respectively. The screening result indicates the 4，5-dihydro-1H-thiochrochromeno［4，3-d］ pyrimidine scaffold becomes a novel moiety with antiproliferative activity and further efforts aiming at developing potent antitumor agents with 4，5-dihydro-1H-thiochrochromeno［4，3-d］ pyrimidine scaffold would be continued in the future. |
| Key words：heterocycle；4，5-dihydro-1H-thiochrochromeno［4，3-d］pyrimidine，antiproliferative activity |
|
基金项目：国家自然科学基金资助项目（20474053）。
|
作者简介：郭德祥（1981-），男，河南南阳人，硕士研究生，从事抗肿瘤新药合成。（E-mail：guodexiang001@163.com）
|
联 系 人： 宫 平（1964-），教授，主要从事新药设计与合成。（E-mail：gongpinggp@126.com）
|
收稿日期： 2011-05-0
|
|