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. 2023 Apr;101(4):896-914.
doi: 10.1111/cbdd.14198. Epub 2023 Jan 29.

Discovery and evaluation of biphenyl derivatives of 2-iminobenzimidazoles as prototype dual PTP1B inhibitors and AMPK activators with in vivo antidiabetic activity

Denis A Babkov  1   2 , Olga N Zhukovskaya  3 , Anastasia A Brigadirova  1 , Diana R Prilepskaya  1 , Alexandra A Kolodina  3 , Abbas Haider S Abbas  3 , Anatolii S Morkovnik  3 , M Elizabeth Sobhia  4 , Ketan Ghosh  4 , Alexander A Spasov  1
Affiliations

Discovery and evaluation of biphenyl derivatives of 2-iminobenzimidazoles as prototype dual PTP1B inhibitors and AMPK activators with in vivo antidiabetic activity

Denis A Babkov et al. Chem Biol Drug Des. 2023 Apr.

Abstract

This work describes the synthesis of series hydrobromides of N-(4-biphenyl)methyl-N'-dialkylaminoethyl-2-iminobenzimidazoles, which, due to the presence of two privileged structural fragments (benzimidazole and biphenyl moieties), can be considered as bi-privileged structures. Compound 7a proved to activate AMP-activated kinase (AMPK) and simultaneously inhibit protein tyrosine phosphatase 1B (PTP1B) with similar potency. This renders it an interesting prototype of potential antidiabetic agents with a dual-target mechanism of action. Using prove of concept in vivo study, we show that dual-targeting compound 7a has a disease-modifying effect in a rat model of type 2 diabetes mellitus via improving insulin sensitivity and lipid metabolism.

Keywords: AMPK; PTP1B; diabetes mellitus; obesity.

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References

REFERENCES

    1. Anisimova, V. A., & Tolpygin, I. E. (2011). Imidazo[1,2-a]benzimidazole derivatives: XXVIII. Syntheses and heterocyclizations on the basis of 1-allyl-2-aminobenzimidazole. Russian Journal of Organic Chemistry, 47, 1346-1353.
    1. Ardiana, F., & Suciati Indrayanto, G. (2015). Profiles of drug substances, excipients and related methodology (Vol. 40, p. 431). Elsevier.
    1. Babkov, D. A., Zhukowskaya, O. N., Borisov, A. V., Babkova, V. A., Sokolova, E. V., Brigadirova, A. A., Litvinov, R. A., Kolodina, A. A., Morkovnik, A. S., Sochnev, V. S., Borodkin, G. S., & Spasov, A. A. (2019). Towards multi-target antidiabetic agents: Discovery of biphenyl-benzimidazole conjugates as AMPK activators. Bioorganic & Medicinal Chemistry Letters, 29, 2443-2447.
    1. Balaramnavar, V. M., Srivastava, R., Rahuja, N., Gupta, S., Rawat, A. K., Varshney, S., Chandasana, H., Chhonker, Y. S., Doharey, P. K., Kumar, S., Gautam, S., Srivastava, S. P., Bhatta, R. S., Saxena, J. K., Gaikwad, A. N., Srivastava, A. K., & Saxena, A. K. (2014). Identification of novel PTP1B inhibitors by pharmacophore based virtual screening, scaffold hopping and docking. European Journal of Medicinal Chemistry, 87, 578-594.
    1. Balaramnavar, V. M., Srivastava, R., Varshney, S., Kumar, S., Rawat, A. K., Chandasana, H., Chhonker, Y. S., Bhatta, R. S., Srivastava, A. K., Gaikwad, A. N., Lakshmi, V., & Saxena, A. K. (2021). Synthesis, biological evaluation, and molecular docking study of some new rohitukine analogs as protein tyrosine phosphatase 1B inhibitors. Bioorganic Chemistry, 110, 104829.

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