Advertisement

Pharmaceutical Chemistry Journal

, Volume 53, Issue 2, pp 118–124 | Cite as

Synthesis and Anticonvulsant Activity of N-Substituted 4-Amino-3-Nitrocoumarins

  • G. V. MokrovEmail author
  • V. L. Savel’ev
  • T. A. Voronina
  • S. A. Litvinova
  • I. G. Kovalev
  • L. N. Nerobkova
  • A. O. Dmitrienko
  • T. A. Gudasheva
  • S. B. Seredenin
Article
  • 10 Downloads

The synthesis and anticonvulsant activity of new coumarin derivatives are reported. N-(3-Nitrocoumarin-4-yl)-4-aminobutyric acid (1a) at doses of 60 and 80 mg/kg (in the MES test) and methyl N-(3,6-dinitrocoumarin-4-yl)-4-aminobutyrate (1e) at doses of 20 and 40 mg/kg (in the corazole antagonism test) possessed the greatest anticonvulsant activity of the synthesized compounds. The results indicated that the coumarin derivatives were promising for further development as potential anticonvulsant agents.

Keywords

coumarins anticonvulsant activity maximum electric shock test corazole antagonism test 

Notes

Acknowledgments

A. O. Dmitrienko thanks the Russian Science Foundation (Project No. 16-13-10404) for financial support for the structural studies of 1a.

References

  1. 1.
    G. N. Avakyan, Ya. B. Yudel'son, N. N. Maslova, and E. I. Gusev, Zh. Nevropatol. Psikhiatr., 9, 9 – 15 (2003).Google Scholar
  2. 2.
    V. Rempel, N. Volz, F. Glaser, et al., J. Med. Chem., 56(11), 4798 – 4810 (2013).CrossRefGoogle Scholar
  3. 3.
    M. Curini, G. Cravotto, F. Epifano, and G. Giannone, Curr. Med. Chem., 13, 199 – 222 (2006).CrossRefGoogle Scholar
  4. 4.
    A. A. Emmanuel-Giota, K. C. Fylaktakidou, D. J. Hadjipavlou-Litina, et al., J. Heterocycl. Chem., 38, 717 – 722 (2001).CrossRefGoogle Scholar
  5. 5.
    Z. M. Nofal, M. I. El-Zahar, and S. S. Abd El-Karim, Molecules, 5, 99 – 113 (2000).CrossRefGoogle Scholar
  6. 6.
    B. Dekic, V. Dekic, N. Radulovic, et al., Chem. Pap., 64, 354 – 359 (2010).CrossRefGoogle Scholar
  7. 7.
    J. Xu, J. Ai, S. Liu, et al., Org. Biomol. Chem., 12(22), 3721 – 3734 (2014).CrossRefGoogle Scholar
  8. 8.
    V. L. Savel’ev, O. S. Artamonova, and V. A. Zagorevskii, Khim. Geterotsikl. Soedin., No. 8, 1147 (1972).Google Scholar
  9. 9.
    V. L. Savel’ev, O. S. Artamonova, and V. S. Troitskaya, Khim. Geterotsikl. Soedin., No. 7, 885 – 890 (1973).Google Scholar
  10. 10.
    J. D. H. Donnay and D. Harker, Am. Mineral., 22(5), 446 – 467 (1937).Google Scholar
  11. 11.
    C. F. Macrae, I. J. Bruno, J. A. Chisholm, et al., J. Appl. Crystallogr., 41(2), 466 – 470 (2008).CrossRefGoogle Scholar
  12. 12.
    T. A. Voronina and L. N. Nerobkova, “Methodical instructions for studies of anticonvulsant activity of pharmacological substances,” in: Handbook for Preclinical Drug Trials [in Russian], Part 1, NTsEMSP, Grif i K, Moscow, 2012, pp. 235 – 250.Google Scholar
  13. 13.
    W. Loscher, C. P. Fassbender, and B. Nolting, Epilepsy Res., 8(2), 79 – 94 (1991).CrossRefGoogle Scholar
  14. 14.
    W. Loscher, D. Honack, C. P. Fassbender, and B. Nolting, Epilepsy Res., 8, 171 – 189 (1991).CrossRefGoogle Scholar
  15. 15.
    M. Kules, M. Trkovnik, and A. Juric, Acta Pharm. Jugosl., 34, 81 (1984).Google Scholar
  16. 16.
    P. Giannnozzi, S. Baroni, N. Bonini, et al., J. Phys.: Condens. Matter, 21(39), 395502 (2009).Google Scholar
  17. 17.
    J. P. Perdew, K. Burke, and M. Ernzerhof, Phys. Rev. Lett., 77(18), 3865 – 3868 (1996).CrossRefGoogle Scholar
  18. 18.
    S. Grimme, J. Comput. Chem., 27(15), 1787 – 1799 (2006).CrossRefGoogle Scholar
  19. 19.
    D. Vanderbilt, Phys. Rev. B: Condens. Matter Mater. Phys., 41(11), 7892 – 7895 (1990).CrossRefGoogle Scholar
  20. 20.
    A. A. Coelho, J. Appl. Crystallogr., 36(1), 86 – 95 (2003).CrossRefGoogle Scholar
  21. 21.
    Bruker TOPAS 5 User Manual, Karlsruhe, Germany: Bruker AXS GmbH, 2014.Google Scholar
  22. 22.
    V. Favre-Nicolin and R. Cerny, J. Appl. Crystallogr., 35(6), 734 – 743 (2002).CrossRefGoogle Scholar
  23. 23.
    I. J. Bruno, J. C. Cole, and M. Kessler, J. Chem. Inf. Comput. Sci., 44(6), 2133 – 2144 (2004).CrossRefGoogle Scholar
  24. 24.
    W. A. Dollase, J. Appl. Crystallogr., 19(4), 267 – 272 (1986).CrossRefGoogle Scholar
  25. 25.
    A. O. Dmitrienko and I. S. Bushmarinov, J. Appl. Crystallogr., 48(6), 1777 – 1784 (2015).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • G. V. Mokrov
    • 1
    Email author
  • V. L. Savel’ev
    • 1
  • T. A. Voronina
    • 1
  • S. A. Litvinova
    • 1
  • I. G. Kovalev
    • 1
  • L. N. Nerobkova
    • 1
  • A. O. Dmitrienko
    • 2
  • T. A. Gudasheva
    • 1
  • S. B. Seredenin
    • 1
  1. 1.V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical SciencesMoscowRussia
  2. 2.A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of SciencesMoscowRussia

Personalised recommendations