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

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Abstract

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.

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References

  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.

    Article  PubMed  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.

    Article  PubMed  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.

    Article  PubMed  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.

    Article  PubMed  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.

    Article  PubMed  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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Pharmaceutical Chemistry Department, Drug Exploration & Development Chair, College of Pharmacy, king Saud university, Riyadh, 11451, Saudia Arabia

    Nagy M. Khalifa & Mohamed A. Al-Omar

  2. Therapeutical Chemistry Department, Pharmaceutical and Drug Industries Division, National Research Centre, Dokki, 12622, Cairo, Egypt

    Nagy M. Khalifa

  3. Department of Chemistry, University of Southern Denmark, Dk-5230, Odense M, Denmark

    Erik B. Pedersen

  4. Retrovius Laboratory Department of Virology, State Serum Institute, DK-2300, Copenhagen, Denmark

    Claus Nielsen

Authors
  1. Nagy M. Khalifa
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  2. Erik B. Pedersen
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  3. Claus Nielsen
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  4. Mohamed A. Al-Omar
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Correspondence to Nagy M. Khalifa.

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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). https://doi.org/10.1134/S1068162014040050

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  • DOI: https://doi.org/10.1134/S1068162014040050

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