摘要
以金刚烷甲酰氯为起始原料,经亲核取代、吲哚环合及酰化反应制得中间体2-(5-氯-2-金刚烷-1H-吲哚-3-基)-2-氧代乙酰(4); 4与取代胺反应合成了14个新的N-取代2-(5-氯-2-(金刚基-1-基)-1H-吲哚-3-基)-2-氧代乙酰胺衍生物(5a~5n),其结构经~1H NMR,~(13)C NMR和HR-MS(ESI)表征。采用MTT法研究了化合物对人子宫颈癌细胞(Hela)、乳腺癌细胞(MCF-7)和人肝癌细胞(HepG-2)的体外抗肿瘤活性。结果显示:化合物2-(5-氯-2-金刚烷-1H-吲哚-3-基)-N-(3-氯-4-氟苯基)-2-氧代乙酰胺(5e)的体外抑制活性最优,IC_(50)分别为14. 10、10. 56和8. 55μmol·L~(-1)。
The intermediate,2-( 5-chloro-2-amantade-1H-indol-3-group)-2-oxyacetyl( 4),was prepared by three steps of nucleophilic substitution,indol ring and acylation with amantadine formyl chloride as the starting material. Fourteen new N-substituted 2-( 5-chloro-2-( diamond-1-group)-1H-indole-3-group)-2-oxyacetamide derivatives( 5a ~ 5n) were synthesized by reaction of 4 with substituted amines. The structures were characterized by ~1H NMR,13 C NMR and HR-MS( ESI). The in vitro antitumor activities of 5a ~ 5n on human Cervical cancer( Hela),human breast cancer cells( MCF-7)and hepatoma cells( HepG-2) were studied by MTT assay. The results showed that the compound 5e exhibited the best inhibitory activities with IC_(50) of 14. 10,10. 56 and 8. 55 μmol·L~(-1).
引文
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