| 第 41 卷第 2 期 |  | Vol. 41 No. 2 | | 2011 年 4 月 | Apr 2011 |
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所屬欄目：醫藥及中間體
4，5-二氫-1H-硫色烯［4，3-d］嘧啶類(lèi)化合物合成及抗腫瘤細胞增殖活性研究 |
| 郭德祥1，趙曉妍2，何 影1，胡 春1，宮 平1*
（1. 沈陽(yáng)藥科大學(xué) 制藥工程學(xué)院，遼寧 沈陽(yáng)110016；2. 河北省衡水市藥品檢驗所，河北 衡水 053000） |
| 摘 要：以苯硫酚為起始原料經(jīng)Michael加成，環(huán)合得到硫色滿(mǎn)酮，再利用3組分（醛、酮、氨基脒）反應合成了4，5-二氫-1H-硫色烯［4，3-d］嘧啶類(lèi)目標化合物，所合成的5個(gè)目標化合物未見(jiàn)文獻報道，其結構經(jīng)核磁共振氫譜和質(zhì)譜確證。采用MTT法，以吉非替尼（gefitinib）為陽(yáng)性對照藥，測定了目標化合物對肺腺癌A549細胞和非小細胞肺癌H460細胞的體外抗腫瘤增殖活性�；衔颎DX1和GDX2對A549和H460的抑制活性較強，其IC50值分別為0.77、0.67、4.38、3.78 μmol／L。實(shí)驗表明4，5-二氫-1H-硫色烯［4，3-d］嘧啶類(lèi)化合物是一類(lèi)具有新型骨架結構的抗腫瘤化合物，值得進(jìn)一步研究。 |
| 關(guān)鍵詞：雜環(huán)；4，5-二氫-1H-嘧啶并硫色烯；抗腫瘤增殖活性 |
| 中圖分類(lèi)號：TQ254.1 文獻標識碼：A 文章編號：1009-9212（2011）02-0032-04 |
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| 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 |
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基金項目：國家自然科學(xué)基金資助項目（20474053）。
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作者簡(jiǎn)介：郭德祥（1981-），男，河南南陽(yáng)人，碩士研究生，從事抗腫瘤新藥合成。（E-mail：guodexiang001@163.com）
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聯(lián) 系 人： 宮 平（1964-），教授，主要從事新藥設計與合成。（E-mail：gongpinggp@126.com）
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收稿日期： 2011-05-0
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