1-(5-取代糠基)吲哚啉-2-酮衍生物的合成和初步抗肿瘤活性  

Synthesis of 1-furfuryl-indolin-2-one derivatives and preliminary evaluation of their antitumor activities

作　　者：董肖椿[1] 周福生[1] 郑剑斌[1] 闻韧[1] 

机构地区：[1]复旦大学药学院药物化学教研室,上海200032

出　　处：《药学学报》2008年第1期54-59,共6页Acta Pharmaceutica Sinica

基　　金：上海市卫生局青年科研基金资助项目(2006Y14).

摘　　要：为了寻找具有较好抗肿瘤活性的新型吲哚啉-2-酮类化合物,本研究以5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸乙酯与5位不同取代的吲哚啉-2-酮(2a^2d)为原料,首先经缩合得3-吡咯亚甲基-吲哚啉-2-酮(3a^3d),再经N烃化反应得到1-(5-甲酰基糠基)-3-(吡咯亚甲基)-吲哚啉-2-酮(4a^4d),然后与吲哚啉-2-酮缩合得到以5-亚甲基糠基连接的双吲哚啉-2-酮化合物(5a^5d)。所合成的12个新型吲哚啉-2-酮类化合物的结构经核磁共振谱、质谱和元素分析确认。采用四氮唑盐(MTT)还原法测试所合成化合物的体外抗肿瘤活性,结果表明所合成的化合物均有一定的抗肿瘤作用,其中6个化合物对SPC-A1肺癌肿瘤株体外抑制活性优于舒尼替尼,特别是化合物5a^5d,IC50值均小于5μmol.L-1,值得作为抗肿瘤药物先导化合物。In order to find new indolin-2-one derivatives as antitumor agents, a series of 3-pyrrole substituted 1-（5-formyl-2-furanylmethyl） indolin-2-one derivatives were designed and synthesized. 5- 17ormyl-2,4-dimethyl-lH-pyrrole-3-carboxylic acid ethyl ester was condensed with 5-substituted indolin-2- one 2a -2d to afford 3-[ （pyrrol-2-yl）-methylidenyl] indolin-2-ones 3a -3d. Through N-alkylation, 1-（5- formyl-furfuryl）-indolin-2-one 4a- 4d were prepared. Compounds 4a- 4d were then condensed with indolin-2-one to afford bis-indolin-2-one derivatives 5a -5d. The structures of the synthesized compounds were determined by ^1H NMR, MS and element analysis. Antitumor activities of all the synthesized compounds in vitro were tested. All the 12 synthesized compounds possess antitumor activities against SPC- A1 strain. Especially the compounds 5a -5d possess potent antitumor activities better than sunitinib. Their ICon are all below 5μmol · L^-1.

关 键 词：合成 抗肿瘤 吲哚啉-2-酮 衍生物 

分 类 号：R916.2[医药卫生—药学]