Chem. J. Chinese Universities ›› 2014, Vol. 35 ›› Issue (12): 2584.doi: 10.7503/cjcu20140333

• Organic Chemistry • Previous Articles     Next Articles

Design and Synthesis of Pyridinylisoxazoles and Their Anticancer Activities

YANG Hongliang1, XU Guoxing1, BAO Meiying2, ZHANG Dapeng1, LI Zhiwei1,*(), PEI Yazhong1,*()   

  1. 1. The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Sciences,Jilin University, Changchun 130021, China
    2. Changchun Discovery Sciences Co. Ltd., Changchun 130012, China
  • Received:2014-04-09 Online:2014-12-10 Published:2014-11-06
  • Contact: LI Zhiwei,PEI Yazhong E-mail:zwl.jida@gmail.com;peiyz@jlu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(Nos.81172914, 81071743), the Tang Aoqing Professorship Research Grant from Jilin University, China and Jilin Province Talent Development Program, China(No.802110000432)

Abstract:

Based on the X-ray co-crystal structures of reported allosteric kinase inhibitors bound to their corresponding protein kinases, a pharmacophore model was proposed. To examine the validity of this hypothesis, 21 new pyridinylisoxazole derivatives were designed and synthesized. Their structures were confirmed using 1H NMR, 13C NMR and MS data. Their inhibitory effects against human breast cancer cell(MCF-7) proliferation were evaluated. Preliminary results indicated that some of these pyridinylisoxazole derivatives possess potent anti-proliferative activities, with IC50 data in the micromolar range. The mechanism-of-action of these compounds is under investigation.

Key words: Pyridinylisoxazole, Protein kinase, Allosteric kinase inhibitor, Antitumor activity

CLC Number: 

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