Skip to main content
SpringerLink
Log in

Synthesis of Novel Memantine and Rimantadine Derivatives as Promising Drug Candidates

  • Published:
Russian Journal of General Chemistry Aims and scope Submit manuscript

Abstract

A convenient method has been proposed for the preparation of new derivatives of adamantine-based drugs, such as memantine and rimantadine. The synthesis was performed by functionalization of amino-group of memantine and rimantadine by ipso-substitution of cyano-group at C5 position of 1,2,4-triazine scaffold with the corresponding aminoadamantane moieties with subsequent aza-Diels–Alder transformation of 1,2,4-triazine cycle into pyridine one in some cases.

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

Scheme

REFERENCES

  1. Wanka, L., Iqbal, K., and Schreiner, P.R., Chem Rev., 2013, vol. 113, p. 3516. https://doi.org/10.1021/cr100264t

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chupina, T.A., Candidate (Pharm. Sci.) Dissertation, Perm, 2015.

  3. Moiseev, I.K., Kon’kov, S.A., Ovchinnikov, K.A., Kilyaeva, N.M., Bormasheva, K.M., Nechaeva, O.N., Leonova, M.V., Klimochkin, Yu.N., Balakhnin, S.M., Bormotov, N.I., Serova, O.A., and Belanov, E.F., Pharm. Chem. J., 2012, vol. 45, p. 588. https://doi.org/10.1007/s11094-012-0686-3

    Article  CAS  Google Scholar 

  4. Spilovska, K., Zemeka, F., Korabecny, J., Nepovimova, E., Soukup, O., Windisch, M., and Kuca, K., Curr. Med. Chem., 2016, vol. 23, no. 29, p. 3245. https://doi.org/10.2174/0929867323666160525114026

    Article  CAS  PubMed  Google Scholar 

  5. Štimac, A., Šekutor, M., Mlinarić-Majerski, K., Frkanec, L., and Frkanec, R., Molecules, 2017, vol. 22, no. 2, p. 297. https://doi.org/10.3390/molecules22020297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Abaimov, D.A. and Shabalina, A.A., Faramakokinet. Farmakodinam., 2021, vol. 3, p. 3. https://doi.org/10.37489/2587-7836-2021-3-3-11

    Article  Google Scholar 

  7. Odnovorov, A.I., Grebennikova, T.V., and Pleteneva, T.V., Razrabot. Registr. Lekarstv. Sredstv, 2020, vol. 9, no. 1, p. 83. https://doi.org/10.33380/2305-2066-2020-9-1-83-91

    Article  CAS  Google Scholar 

  8. Sayadayn, Kh.S. and Shklovskii, V.M., Doktor.Ru, 2017, no. 130, p. 59.

    Google Scholar 

  9. Ragab, A., Abusaif, M.S., Aboul-Magd, D.S., Wassel, M.M., Elhagali, G.A., and Ammar, Y.A., Drug Dev. Res., 2022, vol. 83, no. 6, p. 1305. https://doi.org/10.1002/ddr.21960

    Article  CAS  PubMed  Google Scholar 

  10. Wassel, M.M., Ammar, Y.A., Ali, G.A.E., Belal, A., Mehany, A.B., and Ragab, A., Bioorg. Chem., 2021, vol. 110, p. 104794. https://doi.org/10.1016/j.bioorg.2021.104794

    Article  CAS  PubMed  Google Scholar 

  11. Trognon, J., Vera, G., Rima, M., Stigliani, J.-L., Amielet, L., El Hage, S., Lajoie, B., Roques, C., and El Garah, F., Pharmaceuticals, 2022, vol. 15, no. 4, p. 417. https://doi.org/10.3390/ph15040417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Patent WO 20010174778 A1, 2021.

  13. Munk, S.A., Lai, R.K., Burke, J.E., Arasasingham, P.N., Kharlamb, A.B., Manlapaz, C.A., Padillo, E.U., Wijono, M.K., Hasson, D.W., Wheeler, L.A., and Garst, M.E., J. Med. Chem., 1996, vol. 39, no. 6, p. 1193. https://doi.org/10.1021/jm960012o

    Article  CAS  PubMed  Google Scholar 

  14. Garaev, T.M., Odnovorov, A.I., Kirillova, E.S., Burtseva, E.I., Finogenova, M.P., Mukasheva, E.A., and Grebennikova, T.V., Voprosy Virusolog., 2020, vol. 65, no. 1, p. 16. https://doi.org/10.36233/0507-4088-2020-65-1-16-20

    Article  CAS  Google Scholar 

  15. Jin, H., Cianchetta, G., Devasagayaraj, A., Gu, K., Marinelli, B., Samala, L., Scott, S., Stouch, T., Tunoori, A., Wang, Y., Zang, Y., Zhang, Ch., Kimball, S.D., Main, A.J., Ding, Zh.-M., Sun, W., Yang, Q., Yu, X.-Q., Powell, D.R., Wilson, A., Liu, Q., and Shi, Zh.-C., Bioorg. Med. Chem. Lett., 2009, vol. 19, p. 5229. https://doi.org/10.1016/j.bmcl.2009.07.005

    Article  CAS  PubMed  Google Scholar 

  16. Patent US 20210139526 A1, 2021.

  17. Ahmadi, A., Khalili, M., Barzin, M., Pooladi, M., Bakhtiari, F., Barjeste, M., and Nahri-Niknafs, B., Monatsh. Chem., 2016, vol. 147, p. 457. https://doi.org/10.1007/s00706-015-1472-1

    Article  CAS  Google Scholar 

  18. Zhang, F.G., Chen, Zh., Tang, X., and Ma, J.-A., Chem. Rev., 2021, vol. 121, no. 23, p. 14555. https://doi.org/10.1021/acs.chemrev.1c00611

    Article  CAS  PubMed  Google Scholar 

  19. Prokhorov, A.M. and Kozhevnikov, D.N., Chem. Heterocycl. Compd., 2012, vol. 48, p. 1153. https://doi.org/10.1007/s10593-012-1117-9

    Article  CAS  Google Scholar 

  20. Kozhevnikov, D.N., Kozhevnikov, V.N., Prokhorov, A.M., Ustinova, M.M., Rusinov, V.L., Chupakhin, O.N., Aleksandrov, G.G., and König, B., Tetrahedron Lett., 2006, vol. 47, no. 6, p. 869. https://doi.org/10.1016/j.tetlet.2005.12.006

    Article  CAS  Google Scholar 

  21. Al-Qawasmeh, R.A., Salameh, B.A., AlRazim, R., AlDamen, M.A., and Voelter, W., Lett. Org. Chem., 2014, vol. 11, no. 7, p. 513. https://doi.org/10.2174/15701786113106660063

    Article  CAS  Google Scholar 

  22. Matveev, A.I. and Moiseev, I.K., Chem. Heterocycl. Compd., 1989, vol. 25, p. 232. https://doi.org/10.1007/BF00479931

    Article  Google Scholar 

  23. Lukin, A., Vedekhina, T., Tovpeko, D., Zhurilo, N., and Krasavin, M., RSC Adv., 2016, vol. 6, p. 57956. https://doi.org/10.1039/C6RA12664B

    Article  CAS  Google Scholar 

  24. Krinochkin, A.P., Kopchuk, D.S., Giri, K., Shtaitz, Y.K., Starnovskaya, E.S., Khalymbadzha, I.A., Drokin, R.A., Ulomsky, E.N., Santra, S., Zyryanov, G.V., Rusinov, V.L., and Chupakhin, O.N., ChemistrySelect, 2018, vol. 3, p. 8202. https://doi.org/10.1002/slct.201801244

    Article  CAS  Google Scholar 

  25. Chopra, S., Koolpe, G.A., Tambo-ong, A.A., Matsuyama, K.N., Ryan, K.J., Tran, T.B., Doppalapudi, R.S., Riccio, E.S., Iyer, L.V., Green, C.E., Wan, B., Franzblau, S.G., and Madrid, P.B., J. Med. Chem., 2012, vol. 55, no. 13, p. 6047. https://doi.org/10.1021/jm300123s

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Patent WO 2019191229 A1, 2021.

  27. Patent WO 2002098873 A1, 2021.

  28. Patent WO 2013142269 A1, 2021.

  29. North, E.J., Scherman, M.S., Bruhn, D.F., Scarborough, J.S., Maddox, M.M., Jones, V., Grzegorzewicz, A., Yang, L., Hess, T., Morisseau, C., Jackson, M., McNeil, M.R., and Lee, R.E., Bioorg. Med. Chem., 2013, vol. 21, no. 9, p. 2587. https://doi.org/10.1016/j.bmc.2013.02.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kozhevnikov, D.N., Nikitina, T.N., Rusinov, V.L., and Chupakhin, O.N., Mendeleev Commun., 2000, vol. 10, p. 117. https://doi.org/10.1070/MC2000v010n03ABEH001255

    Article  Google Scholar 

  31. Zhu, Z. and Boger, D.L., J. Org. Chem., 2022, vol. 87, no. 9, p. 6288. https://doi.org/10.1021/acs.joc.2c00543

    Article  CAS  PubMed Central  Google Scholar 

  32. Kozhevnikov, D.N., Kozhevnikov, V.N., Kovalev, I.S., Rusinov, V.L., Chupakhin, O.N., and Aleksandrov, G.G., Russ. J. Org. Chem., 2002, vol. 38, p. 744. https://doi.org/10.1023/A:1019631610505

    Article  CAS  Google Scholar 

  33. Kopchuk, D.S., Chepchugov, N.V., Kovalev, I.S., Santra, S., Rahman, M., Giri, K., Zyryanov, G.V., Majee, A., Charushin, V.N., and Chupakhin, O.N., RSC Adv., 2017, vol. 7, p. 9610. https://doi.org/10.1039/c6ra26305d

    Article  CAS  Google Scholar 

  34. Shabunina, O.V., Shtaitz, Y.K., Kopchuk, D.S., Krinochkin, A.P., Santra, S., Zyryanov, G.V., Wang, Zh., Rusinov, V.L., and Chupakhin, O.N., Chem. Heterocycl. Compd., 2021, vol. 57, p. 462. https://doi.org/10.1007/s10593-021-02924-4

    Article  CAS  Google Scholar 

  35. Savchuk, M.I., Starnovskaya, E.S., Shtaitz, Y.K., Kopchuk, D.S., Nosova, E.V., Zyryanov, G.V., Rusinov, V.L., and Chupakhin, O.N., Russ. J. Gen. Chem., 2018, vol. 88, no. 10, p. 2213. https://doi.org/10.1134/S1070363218100316

    Article  CAS  Google Scholar 

  36. Guda, M.R., Valieva, M.I., Kopchuk, D.S., Aluru, R., Khasanov, A.F., Taniya, O.S., Novikov, A.S., Zyryanov, G.V., and Ranu, B.C., J. Fluoresc., 2023. https://doi.org/10.1007/s10895-023-03304-1

  37. Kozhevnikov, V.N., Kozhevnikov, D.N., Nikitina, T.V., Rusinov, V.L., Chupakhin, O.N., Zabel, M., and König, B., J. Org. Chem., 2003, vol. 68, no. 7, p. 2882. https://doi.org/10.1021/jo0267955

    Article  CAS  PubMed  Google Scholar 

  38. Krinochkin, A.P., Shtaitz, Ya.K., Kudryashova, E.A., Ladin, E.D., Kopchuk, D.S., Zyryanov, G.V., Shafran, Yu.M., Nosova, E.V., and Chupakhin, O.N., Doklady Chem., 2022, vol. 504, p. 79. https://doi.org/10.1134/S0012500822600146

    Article  CAS  Google Scholar 

  39. Sarkar, A., Santra, S., Kundu, S.K., Hajra, A., Zyryanov, G.V., Chupakhin, O.N., Charushin, V.N., and Majee, A., Green Chem., 2016, vol. 18, p. 4475. https://doi.org/10.1039/C6GC01279E

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

This work was carried out using the equipment of the Center for Collective Use “Spectroscopy and Analysis of Organic Compounds.”

Funding

This work was supported by the Russian Science Foundation (grant no. 23-73-10158, https://rscf.ru/project/23-73-10158/).

Author information

Authors and Affiliations

  1. Ural Federal University, 620002, Yekaterinburg, Russia

    Ya. K. Shtaitz, E. D. Ladin, N. V. Slovesnova, K. D. Krasnoperova, D. S. Kopchuk, G. V. Zyryanov & V. L. Rusinov

  2. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 620219, Yekaterinburg, Russia

    E. D. Ladin, D. S. Kopchuk, G. V. Zyryanov & V. L. Rusinov

  3. Ural State Medical University, 620028, Yekaterinburg, Russia

    N. V. Slovesnova

Authors
  1. Ya. K. Shtaitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. D. Ladin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. V. Slovesnova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. D. Krasnoperova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. S. Kopchuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. V. Zyryanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. L. Rusinov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ya. K. Shtaitz.

Ethics declarations

The authors declare no conflict of interest.

Additional information

To the 85th Anniversary of B.A. Trofimov

Publisher's Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shtaitz, Y.K., Ladin, E.D., Slovesnova, N.V. et al. Synthesis of Novel Memantine and Rimantadine Derivatives as Promising Drug Candidates. Russ J Gen Chem 93 (Suppl 1), S100–S105 (2023). https://doi.org/10.1134/S1070363223140244

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070363223140244

Keywords:

Search

Navigation