Skip to main content
SpringerLink
Log in

Exploring the influence of the substituent at position 4 in a series of 3,4-dihydropyrimidin-2(1H)-one A2B adenosine receptor antagonists

  • Published:
Chemistry of Heterocyclic Compounds Aims and scope

In the context of a program to identify selective adenosine A2B receptor antagonists, we have obtained a focused library of 4-substituted 3,4-dihydropyrimidin-2(1H)-ones and its affinity for the four human adenosine receptor subtypes was determined. The synthesis was accomplished by using an experimentally simple and efficient Biginelli approach. The biological evaluation of the library revealed that all the documented derivatives exhibit low or negligible affinity for the A2B receptor, thus highlighting the critical importance of the substituent at position 4 of the 3,4-dihydropyrimidin-2(1H)-one chemotype.

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

Figure 1.
Scheme 1

Similar content being viewed by others

References

  1. Fredholm, B. B.; Arslan, G.; Halldner, L.; Kull, B.; Shulte, G.; Wasserman, W. Naunyn-Schmiedeberg's Arch. Pharmacol. 2000, 362, 299.

    Article  Google Scholar 

  2. Lennarz, W. J., Lane, M. D. Biol. Chem. 2004, 1, 34.

    Google Scholar 

  3. Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Linden, J.; Muller, C. E. Pharmacol. Rev. 2011, 63, 1.

    Article  CAS  Google Scholar 

  4. Moro, S.; Deflorian, F.; Bacilieri, M.; Spalluto, G. Curr. Pharm. Des. 2006, 12, 2175.

    Article  CAS  Google Scholar 

  5. Fredholm, B. B.; Irenius, E.; Kull, B.; Schulte, G. Biochem. Pharmacol. 2001, 61, 443.

    Article  CAS  Google Scholar 

  6. Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology; Wilson, C. N.; Mustafa, S. J.,Eds.; Springer-Verlag: Berlin, Heidelberg, 2009, Vol. 193.

  7. Baraldi, P. G.; Tabrizi, M. A.; Gessi, S.; Borea, P. A. Chem. Rev. 2008, 108, 238.

    Article  CAS  Google Scholar 

  8. Jacobson, K. A.; Gao, Z. G. Nat. Rev. Drug Discovery 2006, 5, 247.

    Article  CAS  Google Scholar 

  9. Pierce, K. D.; Furlong, T. J.; Selbie, L. A.; Shine, J. Biochem. Biophys. Res. Commun. 1992, 187, 86.

    Article  CAS  Google Scholar 

  10. Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Klotz, K. N.; Linden, J. Pharmacol. Rev. 2001, 53, 527.

    CAS  Google Scholar 

  11. Aherne, C. M.; Kewley, E. M.; Eltzschig, H. K. Biochim. Biophys. Acta 2011, 1808, 1329.

    Article  CAS  Google Scholar 

  12. Cacciari, B.; Pastorin, G.; Bolcato, C.; Spalluto, G.; Bacilieri, M.; Moro, S. Mini Rev. Med. Chem. 2005, 5, 1053.

    Article  CAS  Google Scholar 

  13. Crespo, A.; El Maatougui, A.; Biagini, P.; Azuaje, J.; Coelho, A.; Brea, J.; Loza, M. I.; Cadavid, M. I.; García-Mera, X. Gutiérrez-de-Terán, H.; Sotelo, E. ACS Med. Chem. Lett. 2013, 4, 1031.

    Article  CAS  Google Scholar 

  14. Sun, Q.; Wang, Y.; Ge, Z.; Cheng, T.; Li, R. Synthesis 2004, 1047.

  15. Kappe, C. O. Eur. J. Med. Chem. 2000, 35, 1043.

    Article  CAS  Google Scholar 

  16. Dömling, A. Chem. Rev. 2006, 106, 17.

    Article  Google Scholar 

  17. Al Maatougui, A.; Azuaje, J.; González-Gómez, M.; Miguez, G.; Crespo, A.; Carbajales, C.; Escalante, L.; García-Mera, X.; Gutiérrez-de-Terán, H.; Sotelo, E. J. Med. Chem. 2016, 59, 1967.

    Article  Google Scholar 

  18. Xu, F.; Wang, J. J.; Tian, Y. P. Synth. Commun. 2008, 38, 1299.

    Article  CAS  Google Scholar 

  19. Gholap, A. R.; Venkatesan, K.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. Green Chem. 2004, 6, 147.

    Article  CAS  Google Scholar 

  20. Song, Q.; An, X.; Che, F.; Shen, T. J. Heterocycl. Chem. 2015, 52, 1496.

    Article  CAS  Google Scholar 

  21. Cepanec, I.; Litvic, M.; Bartolincic, A.; Lovric, M. Tetrahedron 2005, 61, 4275.

    Article  CAS  Google Scholar 

  22. Hajipour, A. R.; Khazdooz, L.; Zarei, A. Synth. Commun. 2011, 41, 2200.

    Article  CAS  Google Scholar 

  23. Chitra, S.; Devanathan, D.; Pandiarajan, K. Eur. J. Med. Chem. 2010, 45, 367.

    Article  CAS  Google Scholar 

  24. Niknam, K.; Zolfigol, M. A.; Hossieninejad, Z.; Daneshvar, N. Chin. J. Catal. 2007, 28, 591.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the Concellería de Cultura, Educación e Ordenación Universitaria of the Galician Government (grant GPC2014/03), Centro Singular de Investigación de Galicia Accreditation 2016–2019 (ED431G/09), and the European Regional Development Fund (ERDF). Our laboratories are part of the European COST Actions CM1207 (GLISTEN) and CM15135 (MuTaLig).

Author information

Authors and Affiliations

  1. Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, 1578, Santiago de Compostela, Spain

    Abel Crespo, Abdelaziz El Maatougui, Jhonny Azuaje, Luz Escalante, María Majellaro & Eddy Sotelo

  2. Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 1578, Santiago de Compostela, Spain

    Abel Crespo, Abdelaziz El Maatougui, Jhonny Azuaje, Luz Escalante, María Majellaro & Eddy Sotelo

  3. Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, 1578, Santiago de Compostela, Spain

    María Isabel Loza, José Brea & María Isabel Cadavid

  4. Department of Cell and Molecular Biology, Uppsala Biomedicinska Centrum (BMC), Uppsala University, Husarg. 3, SE-7512, Uppsala, Sweden

    Hugo Gutiérrez-de-Terán

Authors
  1. Abel Crespo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdelaziz El Maatougui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jhonny Azuaje
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luz Escalante
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María Majellaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María Isabel Loza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José Brea
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. María Isabel Cadavid
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hugo Gutiérrez-de-Terán
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eddy Sotelo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eddy Sotelo.

Additional information

Published in Khimiya Geterotsiklicheskikh Soedinenii, 2017, 53(3), 316–322

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Crespo, A., El Maatougui, A., Azuaje, J. et al. Exploring the influence of the substituent at position 4 in a series of 3,4-dihydropyrimidin-2(1H)-one A2B adenosine receptor antagonists. Chem Heterocycl Comp 53, 316–321 (2017). https://doi.org/10.1007/s10593-017-2054-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10593-017-2054-4

Keywords

Search

Navigation