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Chinese Journal of Organic Chemistry >

2014 , Vol. 34 >Issue 7: 1407 - 1416

DOI: https://doi.org/10.6023/cjoc201401004

ARTICLE

4-(Pyrimidin-2-ylamino)benzamide Derivatives：Design, Synthesis, and Hedgehog Signaling Pathway Inhibition Study

  • Zhang Liandi ,
  • Xin Minhang ,
  • Wen Jun ,
  • Tang Feng ,
  • Tu Chongxing ,
  • Shen Han ,
  • Wei Ping
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  • a College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211800;
    b Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing 210042;
    c School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061

Received date: 2014-01-05

  Revised date: 2014-02-16

  Online published: 2014-03-26

Supported by

Project supported by the National Major Science and Technology Project of China (Innovation and Development of New Drugs, No. 2011ZX09401-008).

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Abstract

Hedgehog signaling pathway is a new therapeutic target for interventional cancer treatment. A novel series of 4-(pyrimidin-2-ylamino)benzamide derivatives were designed as hedgehog signaling pathway inhibitors based on our previously reported lead compound 1 and its structure activity relationship. Fourteen compounds were synthesized and the inhibitory effects on hedgehog signaling pathway of these compounds were evaluated. The results demonstrated that all the compounds presented good potency against hedgehog signaling pathway, and compound 8e was the most potent one with an IC50 value of 5.0 nmol·L-1, more potent than GDC-0449. Likewise, compound 8e displayed improved pharmacokinetic properties.

Key words： hedgehog signaling pathway; 4-(pyrimidin-2-ylamino)benzamide; synthesis; inhibition

Cite this article

Zhang Liandi , Xin Minhang , Wen Jun , Tang Feng , Tu Chongxing , Shen Han , Wei Ping . 4-(Pyrimidin-2-ylamino)benzamide Derivatives：Design, Synthesis, and Hedgehog Signaling Pathway Inhibition Study[J]. Chinese Journal of Organic Chemistry, 2014 , 34(7) : 1407 -1416 . DOI: 10.6023/cjoc201401004

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