Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Tetrahydroisoquinoline-Based Non-Peptidomimetic Plasmepsin Inhibitors

A series of tetrahydroisoquinoline derivatives containing different aryl substituents were designed and synthesized using Pictet–Spengler reaction as the key step. The synthesized tetrahydroisoquinoline derivatives displayed micromolar inhibitory activity against plasmepsins I and II.

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

Figure 1.
Figure 2.
Figure 3.


  1. 1.

    Wells, T. N. C.; Hooft van Huijsduijnen, R.; Van Voorhis, W. C. Nat. Rev. Drug Discovery2015, 14, 424.

  2. 2.

    Wells, T. N.; Alonso, P. L.; Gutteridge, W. E. Nat. Rev. Drug Discovery2009, 8, 879.

  3. 3.

    Schlitzer, M. Arch. Pharm. 2008, 341, 149.

  4. 4.

    Ersmark, K.; Samuelsson, B.; Hallberg, A. Med. Res. Rev. 2006, 26, 626.

  5. 5.

    Miller, W. A., III; Teye, J.; Achieng, A. O.; Mogire, R. M.; Akala, H.; Ong'echa, J. M.; Rathi, B.; Durvasula, R.; Kempaiah, P.; Kwofie, S. K. Curr. Top. Med. Chem. 2018, 18, 2022.

  6. 6.

    Bobrovs, R.; Jaudzems, K.; Jirgensons, A. J. Med. Chem. 2019, 62, 8931.

  7. 7.

    Kinena, L.; Leitis, G.; Kanepe-Lapsa, I.; Bobrovs, R.; Jaudzems, K.; Ozola, V.; Suna, E.; Jirgensons, A. Arch. Pharm.2018, 351, 1800151.

  8. 8.

    Huizing, A. P.; Mondal, M.; Hirsch, A. K. H. J. Med. Chem. 2015, 58, 5151.

  9. 9.

    Rasina, D.; Otikovs, M.; Leitans, J.; Recacha, R.; Borysov, O. V.; Kanepe-Lapsa, I.; Domraceva, I.; Pantelejevs, T.; Tars, K.; Blackman, M. J.; Jaudzems, K., Jirgensons, A. J. Med. Chem. 2016, 59, 374.

  10. 10.

    Boss, C.; Richard-Bildstein, S.; Weller, T.; Fischli, W.; Meyer, S.; Binkert, C. Curr. Med. Chem.2003, 10, 883.

  11. 11.

    Boss, C.; Corminboeuf, O.; Grisostomi, C.; Meyer, S.; Jones, A. F.; Prade, L.; Binkert, C.; Fischli, W.; Weller, T.; Bur, D. ChemMedChem2006, 1, 1341.

  12. 12.

    Prade, L.; Jones, A. F.; Boss, C.; Richard-Bildstein, S.; Meyer, S.; Binkert, C.; Bur, D. J. Biol. Chem. 2005, 280, 23837.

  13. 13.

    Specker, E.; Böttcher, J.; Heine, A.; Sotriffer, C. A.; Lilie, H.; Schoop, A.; Müller, G.; Griebenow, N.; Klebe, G. J. Med. Chem. 2005, 48, 6607.

  14. 14.

    Fang, X.; Yin, Y.; Chen, Y. T.; Yao, L.; Wang, B.; Cameron, M. D.; Lin, L.; Khan, S.; Ruiz, C.; Schröter, T.; Grant, W.; Weiser, A.; Pocas, J.; Pachori, A.; Schürer, S.; LoGrasso, P.; Feng, Y. J. Med. Chem.2010, 53, 5727.

  15. 15.

    Aggarwal, V. K.; Humphries, P. S.; Fenwick, A. J. Chem. Soc., Perkin Trans. 11999, 2883.

  16. 16.

    Chae, J. Arch. Pharmacal Res. 2008, 31, 305.

  17. 17.

    Hanthorn, J. J.; Valgimigli, L.; Pratt, D. A. J. Org. Chem. 2012, 77, 6908.

  18. 18.

    Trott, O.; Olson, A. J. J. Comput. Chem. 2010, 31, 455.

  19. 19.

    Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschman, H. J. Appl. Crystallogr.2009, 42, 339.

  20. 20.

    Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Adv.2015, A71, 3.

  21. 21.

    Bourhis, L. J.; Dolomanov, O. V.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. Acta Crystallogr., Sect. A.: Found. Adv.2015, A71, 59.

Download references

Author information

Correspondence to Linda Kinena.

Additional information

Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(1), 60–66

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kinena, L., Ozola, V. Tetrahydroisoquinoline-Based Non-Peptidomimetic Plasmepsin Inhibitors. Chem Heterocycl Comp (2020).

Download citation


  • plasmepsins
  • tetrahydroisoquinoline
  • malaria
  • Pictet–Spengler reaction
  • X-ray analysis