Skip to main content

Synthesis and evaluation of novel 6-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents


A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the C-6 position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Purity of the compounds has been confirmed by TLC. Structures of these compounds were established on the basis of elemental analyses and spectral studies. Some of the tested compounds showed moderate to potent activities against wildtype HIV-1, and N-1 alkylated derivatives were highly active.

This is a preview of subscription content, access via your institution.


  1. Gallo, R.C., Salahuddin, S.Z., Popovic, M., Shearer, G.M., Kaplan, M., Haynes, B.F., Palker, T.J., Redfield, R., Oleske, J., Safai, B., White, G., Foster, P., and Markham, P.D., Science, 1984, vol. 224, p. 500.

    PubMed  Article  CAS  Google Scholar 

  2. Tronchet, J.M. and Seman, M., Curr. Top. Med. Chem., 2003, vol. 13, p. 1496.

    Article  Google Scholar 

  3. Tarby, C., Curr. Top. Med. Chem., 2005, vol. 4, p. 1045.

    Article  Google Scholar 

  4. Sluis-Cremer, N., Alpay Temiz, N., and Bahar, I., Curr. HIV Res., 2004, vol. 2, p. 323.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  5. De Clercq, E., Nat. Rev. Drug Disc., 2002, vol. 1, p. 13.

    Article  Google Scholar 

  6. De Clercq, E., J. Med. Chem., 2005, vol. 48, p. 1297.

    PubMed  Article  Google Scholar 

  7. De Clercq, E., Nat. Rev. Drug Disc., 2007, vol. 6, p. 1001.

    Article  Google Scholar 

  8. Baba, M., Tanaka, H., De Clercq, E., Pauwels, R., Balzarini, J., Schols, D., Nakashima, H., Perno, C.F., Walker, R.T., and Miyasaka, T., Biochem. Biophys. Res. Commun., 1989, vol. 165, p. 1375.

    PubMed  Article  CAS  Google Scholar 

  9. Miyasaka, T., Tanaka, T., Baba, M., Hayakawa, H., Walker, R.T., Balzarini, J., and De Clercq, E.J., Med. Chem., 1989, vol. 32, p. 2507.

    Article  CAS  Google Scholar 

  10. Uckun, F.M.J., Enzyme Inhib. Med. Chem., 2006, vol. 21, p. 329.

    Article  Google Scholar 

  11. Artico, M., Drugs Future, 2002, vol. 27, p. 159.

    Article  CAS  Google Scholar 

  12. Marongiu, M.E., Pani, A., Musiu, C., La Colla, P., Mai, A., Sbardella, G., Massa, S., and Artico, M., Recent Res. Dev. Med. Chem., 2001, vol. 1, p. 65.

    CAS  Google Scholar 

  13. De Clercq, E., Int. J. Antimicrob. Agents, 2009, vol. 33, p. 307.

    PubMed  Article  Google Scholar 

  14. Mao, C., Sudeck, E.A., Venkatachalam, T.K., and Uckun, F.M., Biochem. Pharmacol., 2000, vol. 6, p. 1251.

    Article  Google Scholar 

  15. Nawrozkij, M.B., Rotili, D., Tarantino, D., Botta, G., Eremiychuk, A.S., Musmuca, I., Ragno, R., Samuele, A., Zanoli, S., Armand, U.M., Clotet-Codina, I., Novakov, I.A., Orlinson, B.S., Maga, G., Est, J.A., and Artico, M.J., Med. Chem., 2008, vol. 51, p. 4641.

    Article  CAS  Google Scholar 

  16. Mai, A., Artico, M., Sbardella, G., Massa, S., Novellino, E., Greco, G., Loi, A.G., Tremontano, E., Marongiu, M.E., and Colla, P.L.J., Med. Chem., 1999, vol. 42, p. 619.

    Article  CAS  Google Scholar 

  17. Petersen, L., Hansen, T.H., Khalifa, N.M., Pedersen, E.B., and Nielsen, C., Synthesis of new MKC-442 analogus containing alkenyl chains or reactive functionalities, in Monatshefte für Chemie, 2002, vol. 133, p. 1031.

    Article  CAS  Google Scholar 

  18. Nielsen, C.M., Bygbjerg, I.C., and Vestergaard, B.F., Lancet, 1987, vol. 1, p. 566.

    PubMed  Article  CAS  Google Scholar 

  19. Mosmann, T., J. Immunol. Methods, 1983, vol. 65, p. 55.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Nagy M. Khalifa.

Additional information

The article is published in the original.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Khalifa, N.M., Pedersen, E.B., Nielsen, C. et al. Synthesis and evaluation of novel 6-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents. Russ J Bioorg Chem 40, 579–585 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • HIV-1 RT
  • S-DABOs analogues
  • HEPTs analogues
  • anti HIV-1 activity