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3-Oxodapagliflozin as a potent and highly selective SGLT2 inhibitor for the treatment of type 2 diabetes

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Abstract

Structural modifications of 3-OH in the glucose moiety of dapagliflozin(1), an approved potent sodium-dependent glucose transporter 2(SGLT2) inhibitor, led to 3-oxodapagliflozin(16), a highly potent and more selective SGLT2 inhibitor[IC50(hSGLT1)/IC50(hSGLT2)=2851 for compound 16 vs. 843 for compound 1]. 3-Oxodapagliflozin(16) exhibited in vitro(IC50=1.0 nmol/L against hSGLT2 for compound 16 vs. 1.3 nmol/L for compound 1) and in vivo activities comparable to those of dapagliflozin(1). The bioactivities of 3-oxodapagliflozin (16) warrant its further evaluation as a promising SGLT2 inhibitor for the treatment of type 2 diabetes.

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References

  1. Fowler M. J., Clin. Diabetes, 2008, 26(2), 77

    Article  Google Scholar 

  2. Hardman T. C., Dubrey S. W., Diabetes Ther., 2011, 2(3), 133

    Article  CAS  Google Scholar 

  3. Washburn W. N., J. Med. Chem., 2009, 52(7), 1785

    Article  CAS  Google Scholar 

  4. Wright E. M., Loo D. D., Hirayama B. A., Physiol. Rev., 2011, 91(2), 733

    Article  CAS  Google Scholar 

  5. Meng M., Ellsworth B. A., Nirschl A. A., McCann P. J., Patel M., Girotra R. N., Wu G., Sher P. M., Morrison E. P., Biller S. A., Zahler R., Deshpande P. P., Pullockaran A., Hagan D. L., Morgan N., Taylor J. R., Obermeier M. T., Humphreys W. G., Khanna A., Discenza L., Robertson J. M., Wang A., Han S., Wetterau J. R., Janovitz E. B., Flint O. P., Whaley J. M., Washburn W. N., J. Med. Chem., 2008, 51(5), 1145

    Article  CAS  Google Scholar 

  6. Nomura S., Sakamaki S., Hongu M., Kawanishi E., Koga Y., Sakamoto T., Yamamoto Y., Ueta K., Kimata H., Nakayama K., Tsuda-Tsukimoto M., J. Med. Chem., 2010, 53(17), 6355

    Article  CAS  Google Scholar 

  7. Zhang L., Wang Y., Xu H., Shi Y., Liu B., Wei Q., Xu W., Tang L., Wang J., Zhao G., Med. Chem., 2014, 10(3), 304

    Article  CAS  Google Scholar 

  8. Xu Q. H., Li J. Z., He J. H., Zhao X., Huo Q. S., Chem. Res. Chinese Universities, 2013, 29(4), 695

    Article  CAS  Google Scholar 

  9. Zhang S., Wang Y. L., Wei Q. C., Xu W. R., Tang L. D., Zhao G. L., Wang J. W., Chin. Chem. Lett., 2013, 24(5), 429

    Article  CAS  Google Scholar 

  10. Green J. E., Bender D. M., Jackson S., O’Donnell M. J., McCarthy J. R., Org. Lett., 2009, 11(4), 807

    Article  CAS  Google Scholar 

  11. Horito S., Asano K., Umemura K., Hashimoto H., Yoshimura J., Carbohydr. Res., 1983, 121, 175

    Article  CAS  Google Scholar 

  12. Yao H. W., Cui C., Li Y. Q., Wang L. Z., Li Z. M., Zhao W. G., Chem. J. Chinese Universities, 2012, 33(7), 1481

    CAS  Google Scholar 

  13. Crich D., Hu T., Cai F., J. Org. Chem., 2008, 73(22), 8942

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, P. R. China

    Shuo Zhang & Jianwu Wang

  2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, P. R. China

    Shuo Zhang, Yuli Wang, Wei Liu, Yafei Xie, Yuqiang Liu, Weiren Xu, Lida Tang & Guilong Zhao

Authors
  1. Shuo Zhang
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  2. Yuli Wang
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  3. Wei Liu
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  4. Yafei Xie
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  5. Yuqiang Liu
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  6. Weiren Xu
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  7. Lida Tang
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  8. Jianwu Wang
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  9. Guilong Zhao
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Corresponding authors

Correspondence to Jianwu Wang or Guilong Zhao.

Additional information

Supported by the National Natural Science Foundation of China(No.21302141), the Key Projects of Tianjin Science and Technology Support Plan, China(No.10ZCKFSH01300) and the Tianjin Municipal Natural Science Foundation, China(No.14JCQNJC12900).

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Zhang, S., Wang, Y., Liu, W. et al. 3-Oxodapagliflozin as a potent and highly selective SGLT2 inhibitor for the treatment of type 2 diabetes. Chem. Res. Chin. Univ. 30, 785–793 (2014). https://doi.org/10.1007/s40242-014-4043-9

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  • DOI: https://doi.org/10.1007/s40242-014-4043-9

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