Research on Chemical Intermediates

, Volume 40, Issue 4, pp 1365–1381

Synthesis and anti-viral activities of some 3-(naphthalen-1-ylmethylene)-5-phenylfuran-2(3H)-one candidates

  • Eman M. Flefel
  • Waled A. Tantawy
  • Randa E. Abdel-Mageid
  • Abd El-Galil E. Amr
  • Rolla Nadeem


3-(Naphthalen-1-ylmethylene)-5-phenylfuran-2(3H)-one 1 was prepared and converted into a variety of heterocyclic systems of synthetic and biological importance. Benzylamine was reacted with furanone 1 to afford compounds 2 and 3 according to the reaction conditions. Butanamide 2 was reacted with thionyl chloride or thiourea to give derivatives 4 and 5, respectively. Compound 3 was reacted with ethyl cyanoacetate to give the corresponding pyrrolopyridine derivative 6. Treatment of 1 with hydrazine hydrate afforded compounds 7 and 8 according to the reaction conditions. Also, compound 1 was reacted with phenyl hydrazine, hydroxyl amine, malononitrile or thiourea to give compounds 912, respectively. Cyclization of 7 with ethoxymethylene-malononitrile, ethyl-(ethoxymethylene)cyanoacetate, carbon disulphide or acetylacetone afforded the corresponding compounds 1316, respectively. Condensation of 7 with p-nitrobenzaldehyde gave the corresponding hydrazone 17, which was treated with thioglycolic acid or chloroacetyl chloride to give compounds 18 and 19, respectively. Also, most of the prepared products were tested for anti-avian influenza virus and revealed promising antiviral activity against H5N1 virus [A/Chicken/Egypt/1/2006 (H5N1)] by determination of both TC50 and ED50 and confirmed by plaque reduction assay on MDCK cells. Compounds 7, 8, 11, 12 and 13 showed the highest effect compared with the other tested compounds.


Furanone Acid hydrazide Anti-avian influenza virus (H5N1) 


  1. 1.
    M.M. Alam, H. Asif, S.M. Hasan, T.A. Suruchi, Eur. J. Med. Chem. 44, 2636 (2009)CrossRefGoogle Scholar
  2. 2.
    A. Kumar, B. Ahmed, Der Pharma Chemica 4, 383 (2012)Google Scholar
  3. 3.
    A. Husain, A. Mumtaz, S. Nadeem, J. Serb. Chem. Soc. 74, 103 (2009)CrossRefGoogle Scholar
  4. 4.
    A. Husain, M.M. Alam, S.M. Hasan, M.S. Yar, Acta Pol. Pharm. Drug Res. 6, 173 (2009)Google Scholar
  5. 5.
    A. Husain, M.M. Alam, M.S. Yar, A. Ahmad, J. Pharm. Res. 4, 3303 (2011)Google Scholar
  6. 6.
    A.I. Hashem, A.S.A. Youssef, K.A. Kandeel, W.S.I. Abou-Elmagd, Eur. J. Med. Chem. 42, 934 (2007)CrossRefGoogle Scholar
  7. 7.
    A. Husain, S.M. Hasan, S. Lal, M.M. Alam, Indian J. Pharm. Sci. 68, 536 (2006)CrossRefGoogle Scholar
  8. 8.
    M.S. Mohamed, R.A. El-Domany, R.H. Abd El-Hameed, Acta Pharm. 59, 145 (2009)CrossRefGoogle Scholar
  9. 9.
    E. Lattmann, D.C. Billington, C.A. Langley, Drug Des. Discov. 6, 243 (1999)Google Scholar
  10. 10.
    J. Clark, M.S. Shohhet, D. Korakas, G.J. Varvounis, Heterocycl. Chem. 30, 1065 (1993)CrossRefGoogle Scholar
  11. 11.
    M. Santagati, M. Modica, A. Santagati, F. Russo, S. Spampinato, Pharmazie 51, 7 (1996)Google Scholar
  12. 12.
    J. Spychala, D. Boykin, W. Wilson, M. Zhao, R. Tidwell, C. Dykstra, J. Hall, S. Jones, R. Schinazi, Eur. J. Med. Chem. 29, 363 (1994)CrossRefGoogle Scholar
  13. 13.
    K. Danel, E.B. Pedersen, C.J. Nielsen, Med. Chem. 41, 191 (1998)CrossRefGoogle Scholar
  14. 14.
    H.H. Sayed, H.S. Abbas, E.M.H. Morsi, E.M. Flefel, Der Pharma Chemica 3, 31 (2011)Google Scholar
  15. 15.
    S.F. Mohamed, E.M. Flefel, A.E. Amr, D.N. Abd El-Shafy, Eur. J. Med. Chem. 45, 1494 (2010)CrossRefGoogle Scholar
  16. 16.
    A.A. Fayed, H.M. Hosni, E.M. Flefel, A.E. Amr, World J. Chem. 4, 58 (2009)Google Scholar
  17. 17.
    E.M. Flefel, M.A. Salama, M. El-Shahat, M.A. El-Hashash, A.F. El-Farargy, Phosphorus Sulfur Silicon 182, 1739 (2007)CrossRefGoogle Scholar
  18. 18.
    Y. Kumar, R. Green, K.Z. Boryska, D.D. Wise, L.L. Wotring, L.B. Townsend, J. Med. Chem. 36, 3843 (1993)CrossRefGoogle Scholar
  19. 19.
    J.G. Michael, M.L. Tachel, L.M. Susan, H.B. John, L.B. Milton, Bioorg. Med. Chem. 12, 1029 (2004)CrossRefGoogle Scholar
  20. 20.
    K.Y. Jung, S.K. Kim, Z.G. Gao, S.G. Ariel, M. Neli, A.J. Denneth, Y.C. Kim, Bioorg. Med. Chem. 12, 613 (2004)CrossRefGoogle Scholar
  21. 21.
    G.F. Brooks, J.S. Butel, S.A. Morse, Pathogenesis and control of viral diseases, in Medical Microbiology, 21st edn., ed. by Jawetz, Melnick, Adelberg’s (Appleton & Lange, Norwalk, 1998), pp. 345–367Google Scholar
  22. 22.
    K.S. Li, Y. Guan, J. Wang, G.J. Smith, K.M. Xu, L. Duan, A.P. Rahardjo, P. Puthavathana, C. Buranathai, T.D. Nguyen, A.T. Estoepangestie, A. Chaisingh, P. Auewarakul, H.T. Long, N.T. Hanh, R.J. Webby, L.L. Poon, H. Chen, K.F. Shortridge, K.Y. Yuen, R.G. Webster, J.S. Peiris, Nature 430, 209 (2004)CrossRefGoogle Scholar
  23. 23.
    A. Moscona, N. Engl. J. Med. 353, 1363 (2005)CrossRefGoogle Scholar
  24. 24.
    A. Moscona, N. Engl. J. Med. 353, 2633 (2005)CrossRefGoogle Scholar
  25. 25.
    T. Mosmann, J. Immunol. Methods 65, 55 (1983)CrossRefGoogle Scholar
  26. 26.
    F.G. Hayden, K.M. Cote, R.G. Jr, Douglas. Antimicrob. Agents Chemother. 17, 865 (1980)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Eman M. Flefel
    • 1
  • Waled A. Tantawy
    • 1
  • Randa E. Abdel-Mageid
    • 1
  • Abd El-Galil E. Amr
    • 2
    • 3
  • Rolla Nadeem
    • 4
  1. 1.Department of PhotochemistryNational Research CentreCairoEgypt
  2. 2.Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC)College of Pharmacy, King Saud UniversityRiyadhSaudi Arabia
  3. 3.Applied Organic Chemistry DepartmentNational Research CenterCairoEgypt
  4. 4.Virology Laboratory, Environmental Research DivisionNational Research CenterCairoEgypt

Personalised recommendations