3-甲氧基-6-取代-5,6-二氢吡咯[3,4-b]吡啶-1-酮的合成与生物活性有机化学.pdfVIP

DOI: 10.6023/cjoc201309033 研究论文 有机化学 Chinese Journal of Organic Chemistry ARTICLE 3-甲氧基-6-取代-5,6-二氢吡咯[3,4-b]吡啶-1-酮的合成与生物活性 孙广龙 张蔚蔚 詹晓平 刘增路 毛振民* (上海交通大学药学院 上海 200240) 摘要 以3- 甲基-2-氰基吡啶为原料, 经水解、酯化、硝化、甲氧基取代、溴代反应制得中间体 3-溴甲基-5- 甲氧基吡啶- 2- 甲酸甲酯(7), 然后中间体与不同的有机胺经环合反应得到一系列新的沙利度胺衍生物 3- 甲氧基-6-取代-5,6-二氢吡咯 [3,4-b]吡啶-7-酮 1a～1l. 其结构经 1H NMR, 13C NMR 及 HRMS 确证. 采用 MTT(噻唑蓝)法测试了目标化合物抑制 HCT-116, MG-63, MCF-7, HUVEC 及 HMVEC 细胞的活性, 结果表明, 几乎所有化合物对人体正常细胞无明显抑制作 用, 化合物 1h～1l 只对MG-63 细胞株有明显的抑制活性, 化合物 1c～1g 对这三种肿瘤细胞都有较强的抑制活性, 其中 化合物 1d 和 1e 活性最强. 关键词 沙利度胺衍生物; 3- 甲基-2-氰基吡啶; 合成; 生物活性 Synthesis and Biological Activities of 3-Methoxy-6-substituted- 5,6-dihydropyrrolo[3,4-b]pyridin-7-ones Sun, Guanglong Zhang, Weiwei Zhan, Xiaoping Liu, Zenglu Mao, Zhenmin* (School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240) Abstract A series of thalidomide derivatives named 3-methoxy-6-substituted 5,6-dihydropyrrolo[3,4-b]pyridin-7-ones 1a～ 1l, which have never been reported in literature, were synthesized from 3-methyl pyridine-2-carboxylic acid methyl ester (7) and different amines by cyclization reaction. The intermediate 7 was produced via hydrolysis, esterification, nitration reaction, methoxy substitution, bromination reaction using 3-methyl-pyridine-2-carbonitrile as the starting material. The structures of all compounds have been confirmed by 1H NMR, 13C NMR and HRMS techniques. The target compounds were evaluated for their inhibitory activity against HCT-116, MG-63, MCF-7, HUVEC and HMVEC cells by MTT (thiazolyl