Dong Xiao-Chun, Zhou Fu-Sheng, Zheng Jian-Bin, Wen Ren
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 200032, China.
Yao Xue Xue Bao. 2008 Jan;43(1):54-9.
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-Formyl-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 IC50 are all below 5 micromol x L(-1).
为了寻找新型吲哚-2-酮衍生物作为抗肿瘤药物，设计并合成了一系列3-吡咯取代的1-(5-甲酰基-2-呋喃甲基)吲哚-2-酮衍生物。5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸乙酯与5-取代吲哚-2-酮2a-2d缩合，得到3-[(吡咯-2-基)-亚甲基]吲哚-2-酮3a-3d。通过N-烷基化反应，制备了1-(5-甲酰基糠基)-吲哚-2-酮4a-4d。然后将化合物4a-4d与吲哚-2-酮缩合，得到双吲哚-2-酮衍生物5a-5d。通过1H NMR、MS和元素分析确定了合成化合物的结构。测试了所有合成化合物的体外抗肿瘤活性。所有12个合成化合物均对SPC-A1细胞株具有抗肿瘤活性。特别是化合物5a-5d具有比舒尼替尼更强的抗肿瘤活性。它们的IC50均低于5 μmol·L(-1)。
