Design, synthesis and biological evaluation of novel antitumor spirotetrahydrothiopyran–oxindole derivatives as potent p53-MDM2 inhibitors

Publication date: 15 October 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 20
Author(s): Changjin Ji, Shengzheng Wang, Shuqiang Chen, Shipeng He, Yan Jiang, Zhenyuan Miao, Jian Li, Chunquan Sheng
p53–MDM2 protein-protein interaction is a promising target for novel antitumor drug development. Previously, we identified a new class of spirotetrahydrothiopyran–oxindole p53–MDM2 inhibitors by novel organocatalytic enantioselective cascade reactions. Herein, a series of new derivatives were designed, synthesized and assayed to investigate the structure-activity relationships. Among them, compound B14 bearing a novel spiroindole–thiopyranopyridone scaffold exhibited potent MDM2 inhibitory activity as well as antitumor activity, which could effectively induce the apoptosis of A549 cancer cells. It represents a promising lead compound for the development of novel antitumor agents.

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