Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors

Yan Bo Tang, Dianyun Lu, Zheng Chen, Chun Hu, Ying Yang, Jin Ying Tian, Fei Ye, Li Wu, Zhong Yin Zhang, Zhiyan Xiao

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Fifteen novel sulfathiazole-related compounds were designed as PTP1B inhibitors based on a previously reported allosteric inhibitor (1) of PTP1B. These compounds were synthesized and evaluated against human recombinant PTP1B. Six compounds (3, 4, 8 and 14-16) exhibited significant inhibitory activity against PTP1B. The most active compound (16) showed IC50 value of 3.2 μM and kinetic analysis indicated that it is a non-competitive inhibitor of PTP1B. Furthermore, compound 16 demonstrated excellent selectivity to PTP1B over other PTPs. It also displayed in vivo insulin sensitizing effect in the insulin resistant mice.

Original languageEnglish (US)
Pages (from-to)2313-2318
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number8
DOIs
StatePublished - Apr 15 2013

Keywords

  • In vivo insulin-sensitising effects
  • PTP1B inhibitors
  • Selectivity

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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  • Cite this

    Tang, Y. B., Lu, D., Chen, Z., Hu, C., Yang, Y., Tian, J. Y., Ye, F., Wu, L., Zhang, Z. Y., & Xiao, Z. (2013). Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors. Bioorganic and Medicinal Chemistry Letters, 23(8), 2313-2318. https://doi.org/10.1016/j.bmcl.2013.02.073