Skip to main content
SpringerLink
Log in

New hybrid compounds bearing pyrrolo[3,2,1-ij]quinolin-2-one and coumarin motifs. Synthesis and evaluation of anticoagulant activity

  • Full Articles
  • Published:
Russian Chemical Bulletin Aims and scope

Abstract

A series of new (E)-4,4,6-trimethyl-1-[2-oxo-2-(2-oxo-2H-chromen-3-yl)ethylidene]-4H-pyrrolo[3,2,1-ij]quinolin-2-ones was synthesized by the aldol condensation of pyrrolo[3,2,1-ij]quinoline-1,2-diones with 3-acetylcoumarins. It was found that this reaction proceeded via the intermediate 1-hydroxy-4,4,6-trimethyl-1-[2-oxo-2-(2-oxo-2H-chromen-3-yl)ethyl]-4H-pyrrolo[3,2,1-ij]quinolin-2-one. Preliminary in vitro screening of the synthesized compounds for anticoagulant activity against coagulation factors Xa and XIa indicated that some of these compounds demonstrated the moderate activity against factor Xa. One compound inhibiting both factors was also revealed.

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

References

  1. K. Lai, K. J. Wierenga, M. Tang, US Pat. 2011/0251236A1, 2011.

  2. M. Toyama, N. Sakakibara, M. Takeda, M. Okamoto, K. Watashi, T. Wakita, M. Sugiyama, M. Mizokami, M. Ikeda, M. Baba, Virus Res., 2019, 271, 197677; DOI: https://doi.org/10.1016/j.virusres.2019.197677.

    Article  CAS  PubMed  Google Scholar 

  3. S. Hou, X. J. Lan, W. Li, X. L. Yan, J. J. Chang, X. H. Yang, W. Sun, J. H. Xiao, S. Li, Bioorg. Chem., 2020, 95, 103556; DOI: https://doi.org/10.1016/j.bioorg.2019.103556.

    Article  CAS  PubMed  Google Scholar 

  4. N. P. Novichikhina, A. S. Shestakov, A. Y. Potapov, E. A. Kosheleva, G. V. Shatalov, V. N. Verezhnikov, D. Y. Vandyshev, I. V. Ledeneva, Kh. S. Shikhaliev, Russ. Chem. Bull., 2020, 69, 787; DOI: https://doi.org/10.1007/s11172-020-2834-3.

    Article  CAS  Google Scholar 

  5. S. M. Medvedeva, Kh. S. Shikhaliev, Molecules, 2022, 27, 4033; DOI: https://doi.org/10.3390/molecules27134033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. R. H. Guenther, J. R. Szewczyk, US Pat. 9,173,886B2, 2015; Chem. Abstrs., 2015, 155, 449496.

  7. S. M. Medvedeva, Kh. S. Shikhaliev, A. A. Geronikaki, P. I. Savosina, D. S. Druzhilovskiy, V. V. Poroikov, SAR QSAR Environ. Res., 2022, 33, 273; DOI: https://doi.org/10.1080/1062936X.2022.2064547.

    Article  CAS  PubMed  Google Scholar 

  8. N. Novichikhina, I. Ilin, A. Tashchilova, A. Sulimov, D. Kutov, I. Ledenyova, M. Krysin, Kh. Shikhaliev, A. Gantseva, E. Gantseva, N. Podoplelova, Molecules, 2020, 25, 1889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. S. M. Medvedeva, A. Yu. Potapov, I. V. Gribkova, E. V. Katkova, V. B. Sulimov, Kh. S. Shikhaliev, Pharm. Chem. J., 2018, 51, 975; DOI: https://doi.org/10.1007/s11094-018-1726-4.

    Article  CAS  Google Scholar 

  10. N. P. Novichikhina, A. A. Skoptsova, A. S. Shestakov, A. Yu. Potapov, E. A. Kosheleva, O. A. Kozaderov, I. V. Ledenyova, N. A. Podoplelova, M. A. Panteleev, Kh. S. Shikhaliev, Russ. J. Org. Chem., 2020, 56, 1550; DOI: https://doi.org/10.1134/S1070428020090080.

    Article  CAS  Google Scholar 

  11. A. Tashchilova, N. Podoplelova, A. Sulimov, D. Kutov, I. Ilin, M. Panteleev, Kh. Shikhaliev, S. Medvedeva, N. Novichikhina, A. Potapov, V. Sulimov, Molecules, 2022, 27, 1234; DOI: https://doi.org/10.3390/molecules27041234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. A. Yu. Potapov, B. V. Paponov, N. A. Podoplelova, M. A. Panteleev, V. A. Polikarchuk, I. V. Ledenyova, N. V. Stolpovskaya, D. V. Kryl’skii, Kh. S. Shikhaliev, Russ. Chem. Bull., 2021, 70, 492; DOI: https://doi.org/10.1007/s11172-021-3114-6.

    Article  CAS  Google Scholar 

  13. A. A. Skoptsova, A. S. Shestakov, I. V. Ledenyova, N. V. Stolpovskaya, N. A. Podoplelova, M. A. Panteleev, B. V. Paponov, O. E. Sidorenko, Kh. S. Shikhaliev, N. P. Novichikhina, ChemistrySelect, 2022, 7, e20220073; DOI: https://doi.org/10.1002/slct.202200730.

    Article  Google Scholar 

  14. V. Kartsev, Kh. S. Shikhaliev, A. Geronikaki, S. M. Medvedeva, I. V. Ledenyova, M. Y. Krysin, A. Petrou, A. Ciric, J. Glamoclija, M. Sokovic, Eur. J. Med. Chem., 2019, 175, 201; DOI: https://doi.org/10.1016/j.ejmech.2019.04.046.

    Article  CAS  PubMed  Google Scholar 

  15. G. X. Pang, C. Niu, N. Mamat, H. A. Aisa, Bioorg, Med. Chem. Lett., 2017, 27, 2674; DOI: https://doi.org/10.1016/j.bmcl.2017.04.039.

    Article  CAS  Google Scholar 

  16. H. B. Lad, R. R. Giri, D. I. Brahmbhatt, Chin. Chem. Lett., 2013, 24, 227; DOI: https://doi.org/10.1016/j.cclet.2013.01.041.

    Article  CAS  Google Scholar 

  17. H. M. Alshibl, E. S. Al-Abdullah, M. E. Haiba, H. M. Alkahtani, G. E. A. Awad, A. H. Mahmoud, B. M. M. Ibrahim, A. Bari, A. Villinger, Molecules, 2020, 25, 3251; DOI: https://doi.org/10.3390/molecules25143251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Y.-P. Liu, G. Yan, Y.-T. Xie, T.-C. Lin, W. Zhang, J. Li, Y.-J. Wu, J.-Y. Zhou, Y.-H. Fu, Bioorg. Chem., 2020, 97, 103699; DOI: https://doi.org/10.1016/j.bioorg.2020.103699.

    Article  CAS  PubMed  Google Scholar 

  19. M. A. Polovinkina, V. P. Osipova, A. D. Osipova, I. V. Kanevskaya, A. L. Ivanova, N. V. Pchelintseva, N. T. Berberova, Russ. Chem. Bull., 2022, 71, 2645; DOI: https://doi.org/10.1007/s11172-022-3694-9.

    Article  CAS  Google Scholar 

  20. A. Kamal, S. Adil, J. Tamboli, B. Siddardha, U. Murthy, Lett. Drug Des. Discov., 2009, 6, 201; DOI: https://doi.org/10.2174/157018009787847855.

    Article  CAS  Google Scholar 

  21. M. Bozdag, A. M. Alafeefy, A. M. Altamimi, D. Vullo, F. Carta, C. T. Supuran, Bioorg. Med. Chem., 2017, 25, 677; DOI: https://doi.org/10.1016/j.bmc.2016.11.039.

    Article  CAS  PubMed  Google Scholar 

  22. S. Taheri, M. Nazifi, M. Mansourian, L. Hosseinzadeh, Y. Shokoohinia, Bioorg. Chem., 2019, 91, 103147; DOI: https://doi.org/10.1016/j.bioorg.2019.103147.

    Article  PubMed  Google Scholar 

  23. S. Chekir, M. Debbabi, A. Regazzetti, D. Dargère, O. Laprévote, H. Jannet, R. Gharbi, Bioorg. Chem., 2018, 80, 189; DOI: https://doi.org/10.1016/j.bioorg.2018.06.005.

    Article  CAS  PubMed  Google Scholar 

  24. S. F. Razavi, M. Khoobi, H. Nadri, A. Sakhteman, A. Moradi, S. Emami, A. Foroumadi, A. Shafiee, Eur. J. Med. Chem., 2013, 64, 252; DOI: https://doi.org/10.1016/j.ejmech.2013.03.021.

    Article  CAS  PubMed  Google Scholar 

  25. S. Ghanei-Nasab, M. Khoobi, F. Hadizadeh, A. Marjani, A. Moradi, H. Nadri, S. Emami, A. Foroumadi, A. Shafiee, Eur. J. Med. Chem., 2016, 121, 40; DOI: https://doi.org/10.1016/j.ejmech.2016.05.014.

    Article  CAS  PubMed  Google Scholar 

  26. W. R. Mahmoud, Y. M. Nissan, M. M. Elsawah, R. H. Refaey, M. F. Ragab, K. M. Amin, Eur. J. Med. Chem., 2019, 182, 111651; DOI: https://doi.org/10.1016/j.ejmech.2019.111651.

    Article  CAS  PubMed  Google Scholar 

  27. H. Li, Y. Yao, L. Li, J. Pharm. Pharmacol., 2017, 69, 1253; DOI: https://doi.org/10.1111/jphp.12774.

    Article  CAS  PubMed  Google Scholar 

  28. M. Mohammadi-Khanaposhtani, N. Ahangar, S. Sobhani, P. H. Masihi, A. Shakiba, M. Saeedi, T. Akbarzadeh, Bioorg. Chem., 2019, 89, 102989; DOI: https://doi.org/10.1016/j.bioorg.2019.102989.

    Article  PubMed  Google Scholar 

  29. S.-B. Wang, H. Liu, G.-Y. Li, J. Li, X.-J. Li, K. Lei, L.-C. Wei, Z.-S. Quan, X.-K. Wang, R.-M. Liu, Pharmacol. Rep., 2019, 71, 1244; DOI: https://doi.org/10.1016/j.pharep.2019.07.011.

    Article  CAS  PubMed  Google Scholar 

  30. M. E. Riveiro, N. De Kimpe, A. Moglioni, R. Vazquez, F. Monczor, C. Shayo, C. Davio, Curr. Med. Chem., 2010, 17, 1325; DOI: https://doi.org/10.2174/092986710790936284.

    Article  CAS  PubMed  Google Scholar 

  31. Y. H. Mekaj, A. Y. Mekaj, S. B. Duci, E. I. Miftari, Ther. Clin. Risk. Manag., 2015, 11, 967; DOI: https://doi.org/10.2147/TCRM.S84210.

    Article  PubMed  PubMed Central  Google Scholar 

  32. H. Yuan, Q. Ma, L. Ye, G. Piao, Molecules, 2016, 21, 559; DOI: https://doi.org/10.3390/molecules21050559.

    Article  PubMed  PubMed Central  Google Scholar 

  33. A. Dorababu, Arch. Pharm., 2022, 355, e2100345; DOI: https://doi.org/10.1002/ardp.202100345.

    Article  Google Scholar 

  34. E. V. Leshcheva, S. M. Medvedeva, Kh. S. Shikhaliev, Zh. Org. Farm. Khim., 2014, 12, No. 2, 15; DOI: https://doi.org/10.24959/ophcj.14.798.

    CAS  Google Scholar 

  35. M. L. Li, Y. J. Ren, M. H. Dong, W. X. Ren, Eur. J. Med. Chem., 2015, 96, 122; DOI: https://doi.org/10.1016/j.ejmech.2015.04.012.

    Article  CAS  PubMed  Google Scholar 

  36. X. Li, T. Guo, Q. Feng, T. Bai, L. Wu, Y. Liu, X. Zheng, J. Jia, J. Pei, S. Wu, Y. Song, Y. Zhang, Eur. J. Med. Chem., 2022, 228, 114035; DOI: https://doi.org/10.1016/j.ejmech.2021.114035.

    Article  CAS  PubMed  Google Scholar 

  37. M. O. Zimmermann, A. Lange, R. Wilcken, M. B. Cieslik, T. E. Exner, A. C. Joerger, P. Koch, F. M. Boeckler, Future Med. Chem., 2014, 6, 617; DOI: https://doi.org/10.4155/fmc.14.20

    Article  CAS  PubMed  Google Scholar 

  38. L. Matesic, J. M. Locke, K. L. Vine, M. Ranson, J. B. Bremner, D. Skropeta, Tetrahedron, 2012, 68, 6810; DOI: https://doi.org/10.1016/j.tet.2012.06.049.

    Article  CAS  Google Scholar 

  39. E. Kojima, Sh. Fujimori, K. Awano, US Pat. US4956372A, 1990.

  40. E. Kojima, K. Saito, US Pat. US5124325A, 1992.

  41. N. P. Novichikhina, A. S. Shestakov, A. A. Skoptsova, Z. E. Ashrafova, N. V. Stolpovskaya, E. A. Kosheleva, G. V. Shatalov, I. V. Ledenyova, Kh. S. Shikhaliev, Russ. J. Org. Chem., 2021, 57, 1592; DOI: https://doi.org/10.1134/S1070428021100043.

    Article  CAS  Google Scholar 

  42. E. V. Leshcheva, Kh. S. Shikhaliev, G. V. Shatalov, G. I. Ermolova, Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol. [Bull. Inst. Higher Educ., Chem. Chem. Technol.], 2003, 46, No. 5, 105 (in Russian).

    CAS  Google Scholar 

  43. F. Mazaheri, B. E. Saatluo, M. M. Baradarani, J. A. Joule, J. Heterocycl. Chem., 2017, 54, 147; DOI: https://doi.org/10.1002/jhet.2555.

    Article  CAS  Google Scholar 

  44. B. E. Saatluo, M. M. Baradarani, J. A. Joule, J. Heterocycl. Chem., 2018, 55, 1176; DOI: https://doi.org/10.1002/jhet.3150.

    Article  CAS  Google Scholar 

  45. S. M. Medvedeva, A. L. Sabynin, Kh. S. Shikhaliev, Russ. Chem. Bull., 2014, 63, 2693; DOI: https://doi.org/10.1007/s11172-014-0801-6.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the staff of the Center for Theoretical Problems of Physicochemical Pharmacology for the in vitro studies of inhibitory activity of the synthesized compounds.

Funding

This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation in the framework of the State Assignment to the Universities in the field of scientific activity for 2023–2025 (Project No. FZGU-2023-0009).

Author information

Authors and Affiliations

  1. Voronezh State University, 1 Universitetskaya pl., 394018, Voronezh, Russian Federation

    A. A. Skoptsova, N. P. Novichikhina, E. A. Kosheleva, M. Yu. Krysin & Kh. S. Shikhaliev

  2. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991, Moscow, Russian Federation

    S. V. Baranin

Authors
  1. A. A. Skoptsova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. P. Novichikhina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Kosheleva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Yu. Krysin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. V. Baranin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kh. S. Shikhaliev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kh. S. Shikhaliev.

Ethics declarations

Animal Testing and Ethics

No human or animal subjects were used in this research.

Conflict of Interest

The authors declare no competing interests.

Additional information

Based on the materials of the VII International Conference “Modern Synthetic Methodologies for Creating Drugs and Functional Materials” (MOSM 2023) dedicated to the 125th birth anniversary of Academician I. Ya. Postovsky (September 10–16, 2023, Yekaterinburg—Perm, Russia).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 12, pp. 2898–2907, December, 2023.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Skoptsova, A.A., Novichikhina, N.P., Kosheleva, E.A. et al. New hybrid compounds bearing pyrrolo[3,2,1-ij]quinolin-2-one and coumarin motifs. Synthesis and evaluation of anticoagulant activity. Russ Chem Bull 72, 2898–2907 (2023). https://doi.org/10.1007/s11172-023-4099-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11172-023-4099-0

Key words

Search

Navigation