Skip to main content
SpringerLink
Log in

Targeted Synthesis of New 5-Phenyl-2-[(E)-Styryl]-1H-Pyrimidin-6-One Derivatives and Their Inhibitory Activity Toward SARS-CoV-2 Major (MPRO) and Papain-Like Proteases (PLPRO)

  • SEARCH FOR NEW DRUGS
  • Published:
Pharmaceutical Chemistry Journal Aims and scope

The use of the 5-phenyl-1H-pyrimidin-6-one scaffold in the search for biologically active compounds with antiviral activity based on the pyrimidin-4-one core present in endogenous substances and drugs was substantiated. The molecular activity and pharmacokinetic descriptors for styryl derivatives of N-substituted 5-phenyl-1H-pyrimidin-6-one were predicted in silico via the SwissADME web service. The lack of crystallographic data and information about the tautomeric form of 2,4-dimethyl-5-phenyl-1H-pyrimidin-6-one necessitated the measurement and analysis of x-ray diffraction patterns of the starting substance to explain the reactivity in the styrylation reaction. New derivatives of 5-phenyl-2-[(E)-styryl]-1H-pyrimidin-6-one were synthesized. Studies of their inhibitory activity toward SARS-CoV-2 major (Mpro) and papain-like proteases (PLpro) revealed their marked antiviral activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  1. X.-J. Zhang, L.-H. Lu, R.-R. Wang, et al., PLoS One, 8(11), e81489 (2013); doi: https://doi.org/10.1371/journal.pone.0081489.

  2. Z. Temesgen and D. S. Siraj, Ther. Clin. Risk Manage., 4(2), 493 – 500 (2008); doi: https://doi.org/10.2147/tcrm.s2268.

  3. D. C. White, T. D. Greenwood, A. L. Downey, et al., Bioorg. Med. Chem., 12(1), 5711 – 5717 (2004); doi: https://doi.org/10.1016/j.bmc.2004.07.068.

    Article  CAS  Google Scholar 

  4. R. G. Paronikyan, Epilepsiya Paroksizm. Sostoyaniya, 9(3), 40 – 46 (2017).

    Google Scholar 

  5. Z. M. Nofal, H. H. Fahmy, E. S. Zarea, and W. El-Eraky, Acta Pol. Pharm. Drug Res., 68(4), 507 – 517 (2011).

    CAS  Google Scholar 

  6. C. M. Bhalgat, M. Irfan Ali, B. Ramesh, and G. Ramu, Arabian J. Chem., 7(6), 986 – 993 (2014); doi: https://doi.org/10.1016/j.arabjc.2010.12.021.

  7. F. Jubeen, A. Liaqat, M. Sultan, et al., Saudi Pharm. J., 27(8), 1164 – 1173 (2019); doi: https://doi.org/10.1016/j.jsps.2019.09.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. A. A. Radwan and F. K. Alanazi, Molecules, 19(9), 13177 – 13187 (2014); doi: https://doi.org/10.3390/molecules190913177.

  9. A. A. Arutyunyan, S. S. Mamyan, G. M. Stepanyan, and R. V. Paronikyan, Khim.-farm. Zh., 47(6), 19 – 21 (2013).

    Google Scholar 

  10. Z. Wang, X. Wang, Y. Kang, et al., Phys. Chem. Chem. Phys., 22(10), 5487 – 5499 (2020); doi: https://doi.org/10.1039/d0cp00370k.

    Article  CAS  PubMed  Google Scholar 

  11. A. B. Umar, A. Uzairu, G. A. Shallangwa, and S. Uba, Future J. Pharm. Sci., 6, Art. No. 61, 1 – 10 (2020); doi: https://doi.org/10.1186/s43094-020-00084-4.

  12. J. W. Visser, J. Appl. Crystallogr., 2, 89 – 95 (1969).

    Article  CAS  Google Scholar 

  13. S. D. Kirik, S. V. Borisov, and V. E. Fedorov, Z. Strukt. Khim., 22, 131 – 135 (1981).

    Google Scholar 

  14. L. A. Solovyov and S. D. Kirik, “Application of simulated annealing approach in powder crystal structure analysis,” Mater. Sci. Forum, 195 – 200 (1993).

  15. V. Favre-Nicolin and R. Cerny, J. Appl. Crystallogr., 35(6), 734 – 743 (2002).

    Article  CAS  Google Scholar 

  16. F. H. Allen, Acta Crystallogr., Sect. B: Struct. Sci., 58(3), 380 – 388 (2002).

  17. S. D. Kirik, Kristallografiya, 30, 185 – 186 (1985).

    CAS  Google Scholar 

  18. H. Yang,W. Xie, X. Xue, et al., PLoS Biol., 3(11), e428 (2005).

    Article  PubMed Central  Google Scholar 

  19. E. Pitsillou, J. Liang, K. Ververis, et al., Front. Chem., 8, 623971 (2020); doi: https://doi.org/10.3389/fchem.2020.623971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. A. A. Arutyunyan, “Study of the synthesis of pyrimidines and polycyclic azaheterocycles,” Author’s Abstract of a Doctoral Dissertation in Chemical Sciences, Yerevan (2017).

  21. I. P. Kodonidi, D. S. Anenko, A. Yu. Terekhov, et al., Farmatsiya, 70(1), 11 – 17 (2021); doi: https://doi.org/10.29296/25419218-2021-01-02.

  22. V. A. Mamedov, D. F. Saifina, A. T. Gubaidullin, et al., Tetrahedron Lett., 51, 6503 – 6506 (2010); doi:https://doi.org/10.1016/j.tetlet.2010.10.007.

  23. D. A. Svetlichnyi and N. S. Fedik, Vestn. SPbGU, Ser. 4: Fiz. Khim., 3(61), 171 – 179 (2016).

Download references

Author information

Authors and Affiliations

  1. Pyatigorsk Medical and Pharmaceutical Institute, Ministry of Health of Russia, 11 Kalinina Prosp., Pyatigorsk, 357532, Russia

    A. S. Rozhkova, I. P. Kodonidi, D. I. Pozdnyakov, V. P. Filippova & N. N. Vdovenko-Martynova

  2. North Caucasian Federal University, 1 Pushkina St., Stavropol, 355017, Russia

    D. S. Anenko

  3. Institute of Chemistry and Chemical Technology, Siberian Federal University, Siberian Branch, Russian Academy of Sciences, 50/24 Akademgorodok St., Krasnoyarsk, 660036, Russia

    S. D. Kirik

Authors
  1. A. S. Rozhkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. P. Kodonidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. S. Anenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. D. Kirik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. I. Pozdnyakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. P. Filippova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N. N. Vdovenko-Martynova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. P. Kodonidi.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 57, No. 8, pp. 20 – 27, August, 2023.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rozhkova, A.S., Kodonidi, I.P., Anenko, D.S. et al. Targeted Synthesis of New 5-Phenyl-2-[(E)-Styryl]-1H-Pyrimidin-6-One Derivatives and Their Inhibitory Activity Toward SARS-CoV-2 Major (MPRO) and Papain-Like Proteases (PLPRO). Pharm Chem J 57, 1189–1196 (2023). https://doi.org/10.1007/s11094-024-03025-0

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-024-03025-0

Keywords

Search

Navigation