Advertisement

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

Synthesis of 2-alkyl-substituted-N6-methyladenine derivatives as potential adenosine receptor ligand

  • 99 Accesses

  • 8 Citations

Abstract

2-(1-Hexynyl), 2-((E)-1-hexenyl) and 2-(n-hexyl)-N6-methyladenines were synthesized, starting from 2-amino-6-chloropurine using palladium-catalyzed coupling as a key step as potential adenosine receptor ligand.

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

References

  1. Cristalli, G., Eleuteri, A., Vittori, S., Volpini, R., Lohse, M. J., and Klotz, K. N. 2-Alkynyl Derivatives of Adenosine-5′-N-ethyluronamide as Selective Agonists at A2 Adenosine Receptors.J. Med. Chem. 35, 2363–2368 (1992).

  2. Daly, J. W. and Jacobson, K. A. Adenosine receptors: selective agonists and antagonists. Inadenosine and adenine nucleotides: from molecular biology to integrative physiology; Beladinelli, L., Pelleg, A., Eds.; Kluwer: Norwell, MA, 1995, pp 157–166.

  3. Erion, M. D. Adenosine receptors as pharmacological targets.Ann. Rep. Med. Chem. 288, 295–304 (1993).

  4. Jacobson, K.A., van Galen, P. J. M., Williams, M. Perspective. Adenosine receptors: pharmacology, structureactivity relationships and therapeutic potential.J. Med. Chem. 35, 407–422 (1992).

  5. Kim, H. O., Ji, X.-D., Melman, N., Olah, M. E., Stiles, G. L., and Jacobson, K. A. Structure-activity relation-ships of 1,3-dialkylxanthine derivatives at rat A3 adeno-sine receptors.J. Med. Chem. 37, 3373–3382 (1994).

  6. Kim, H. O., Ji, X.-D., Siddiqi, S. M., Olah, M. E., Stiles, G. L., Jacobson, K. A. 2-Substitution ofN6-benzyladenosine-5-uronamide enhances selectivity for A3 adenosine receptors.J. Med. Chem. 37, 3614–3621 (1994).

  7. Kim, H. O., Ji, X.-D., Melman, N., Olah, M. E., Stiles, G. L., Jacobson, K. A. Selective ligand for rat A3 adenosine receptors: structure-activity relationships of 1,3-dialkylxanthine 7-riboside derivatives.J. Med. Chem. 37, 4020- 4030 (1994).

  8. Klotz, K.-N., Camaioni, E., Volpini, R., Kachler, S., Vittori, S., Critalli, G.Naunyn-Schmiedebergs Arch. Pharmacol. 360, 103 (1999).

  9. Matsuda, A., Shinozaki, M., Yamaguchi, T., Homma, H., Nomoto, R., Miyasaka, T., Watanabe, Y., Abiru, T. Nucleosides and Nucleotides. 103. 2-Alkyladenosines: A Novel Class of Selective Adenosine A2 Receptor Agonists with Potent Antihypertensive Effects.J. Med. Chem. 35, 241–252. (1992).

  10. Meyerhof, W., Muller-Brechlin, R., Richter, D. Molecular cloning of a novel putative G-protein coupled receptor expressed during rat spermiogenesis.FEBS Lett. 284, 155–160 (1991).

  11. Nair, V., and Richardson, S. G. Modification of Nucleic Acid Bases via Radical Intermediates: Synthesis of Dihalogenated Purine Nucleosides.Synthesis, 670–672 (1982).

  12. Poulsen, S. -A., Quinn, R. J. Adenosine receptors: new opportunities for future drugs.Bioorg & Med. Chem. 6, 619–641 (1998).

  13. Ramkumar, V., Stiles, G. L., Beaven, M. A., and Ali, H. The A3AR is the unique adenosine receptor which facilitates release of allergic mediators in mast cells.J. Biol. Chem. 268, 168871–166890 (1993).

  14. Sebastiao, A. M. and Riberio, J. A. Adenosine A2 receptormediated excitatory actions on the nervous system.Prog. Neurobiol. 48, 167–189 (1996).

  15. Siddiqi, S. M., Jacobson, K. A., Esker, J. L., Olah, M. E., Ji, X.-D., Melman, N., Tiwari, K. N., Secrist, J. A., III, Schneller, S. W., Cristalli, G., Stiles, G. L., Johnson, C. R., and Ijzermann, A. P. Search for new purine- and ribose-modified adenosine analogues as selective agonists and antagonists at adenosine receptors.J. Med. Chem. 1174–1188 (1995).

  16. Stiles, G. L. Adenosine receptors.J. Biol. Chem. 267, 6451–6454 (1992).

  17. Vittori, S., Camaioni, E., Di Francesco, E., Volpini, R., Monopoli, A., Dionisotti, S., Ongini, E., and Cristalli, G. 2-Alkenyl and 2-alkyl derivatives of adenosine and adenosine-5-N-ethyluronamide: different affinity and selectivity ofE- andZ-diastereomers at A2A adenosine receptors.J. Med. Chem. 39, 4211–4217 (1996).

  18. Volpini, R., Costanzi, S., Lambertucci, C., Vittori, S., Kachler, S., Klotz, K.-N., Cristalli, G. Presented at Purines 2000: Biochemical, pharmacological and clinical perspectives.Drug Dev. Res. 50, 66 (2000).

  19. Zhou, Q. Y., Li, C. Y., Olah, M. E., Johnson, R. A., Stiles, G. L., and Civelli, O. Molecular cloning and characterization of an adenosine receptor- the A3 adenosine receptor.Proc. Natl. Acad. Sci. U. S. A. 89, 7432–7436 (1992).

Download references

Author information

Correspondence to Hea Ok Kim.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kim, H.O. Synthesis of 2-alkyl-substituted-N6-methyladenine derivatives as potential adenosine receptor ligand. Arch Pharm Res 24, 508–513 (2001). https://doi.org/10.1007/BF02975154

Download citation

Key words

  • Adenosine receptor
  • Palladium-catalyzed coupling