Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (3): 546-551.DOI: 10.6023/cjoc201309033 Previous Articles     Next Articles



孙广龙, 张蔚蔚, 詹晓平, 刘增路, 毛振民   

  1. 上海交通大学药学院 上海 200240
  • 收稿日期:2013-09-24 修回日期:2013-10-14 发布日期:2013-11-20
  • 通讯作者: 毛振民
  • 基金资助:

    国家科技重大新药创制专项(No. 2010ZX09401-404)资助项目.

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   

  1. School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240
  • Received:2013-09-24 Revised:2013-10-14 Published:2013-11-20
  • Supported by:

    Project supported by the National Significant and Special Project of New Created Drugs (No. 2010ZX09401-404).

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 blue tetrazolium bromide) method, and the results indicated that almost all of them had no obvious inhibitory effect on normal human cells, compounds 1h1l only displayed obvious inhibitory effect on MG-63 cells while compounds 1c1g presented excellent inhibitory activities against all the three kinds of tumor cells, among which compounds 1d and 1e exhibited most potent activities.

Key words: thalidomide derivative, 3-methyl-pyridine-2-carbonitrile, synthesis, biological activity