4-Hydroxy-2-quinolones. 168*. Synthesis, chemical and antitubercular properties of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrazin-2-ylamides

  • I. V. UkrainetsEmail author
  • L. A. Grinevich
  • A. A. Tkach
  • O. V. Bevz
  • S. V. Slobodzian

1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrazin-2-ylamides have been synthesized as potential antitubercular agents. In contrast to pyrimidin-2-ylamides the compounds prepared are brominated by molecular bromine in glacial acetic acid at position 6 of the quinolone ring rather than in the amide part of the molecule. The 1-N-allyl derivative behaves similarly but undergoes halocyclization to give 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline-4-carboxylic acid pyrazin-2-ylamide. A comparative analysis of the antimycobacterial properties of the synthesized compounds and their isomeric pyrimidin-2-ylamides has been carried out.


2-aminopyrazine 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides bromination antitubercular activity X-ray structural analysis 


  1. 1.
    I. V. Ukrainets, N. L. Bereznyakova, A. A. Davidenko, and S. V. Slobodzian, Khim. Geterotsikl. Soedin., 1198 (2009). [Chem. Heterocycl. Comp., 45, 952 (2009)].Google Scholar
  2. 2.
    A. M. El-Naggar, A. M. Abd El-Salam, F. S. Ahmed, M. S. Latif, and F. A. El-Cady, Farmaco [Sci.], 38, 391 (1983).Google Scholar
  3. 3.
    Z. H. Chohan and S. Mushtaq, Pak. J. Pharm. Sci., 13, 21 (2000).Google Scholar
  4. 4.
    K. Gobis, H. Foks, A. Kedzia, M. Wierzchowska, E. Kwapisz, Z. Zwolska, and E. Augustynowicz-Kopeć, Acta Pol. Pharm., 63, 39 (2006).Google Scholar
  5. 5.
    Y. Furuta, K. Takahashi, Y. Fukuda, M. Kuno, T. Kamiyama, K. Kozaki, N. Nomura, H. Egawa, S. Minami, Y. Watanabe, H. Narita, and K. Shiraki, Antimicrob. Agents Chemother., 46, 977 (2002).CrossRefGoogle Scholar
  6. 6.
    J. G. Julander, Y. Furuta, K. Shafer, and R. W. Sidwell, Antimicrob. Agents Chemother., 51, 1962 (2007).CrossRefGoogle Scholar
  7. 7.
    B. B. Gowen, M. H. Wong, K. H. Jung, A. B. Sanders, M. Mendenhall, K. W. Bailey, Y. Furuta, and R. W. Sidwell, Antimicrob. Agents Chemother., 51, 3168 (2007).CrossRefGoogle Scholar
  8. 8.
    H. M. Langford, P. D. Williams, C. F. Homnick, J. P. Vacca, P. J. Felock, K. A. Stillmock, M. V. Witmer, D. J. Hazuda, L. J. Gabryelski, and W. A. Schleif, Bioorg. Med. Chem. Lett., 18, 721 (2008).CrossRefGoogle Scholar
  9. 9.
    A. Kleemann and J. Engel, Pharmaceutical Substances. Synthesis, Patents, Applications, Multimedia Viewer, Version 2.00, Georg Thieme Verlag, Stuttgart (2001).Google Scholar
  10. 10.
    J. Jampilek, M. Dolezal, and V. Buchta, Med. Chem., 3, 277 (2007).CrossRefGoogle Scholar
  11. 11.
    S. C. Ngo, O. Zimhony, W. J. Chung, H. Sayahi, W. R. Jacobs, and J. T. Welch, Antimicrob. Agents Chemother., 51, 2430 (2007).CrossRefGoogle Scholar
  12. 12.
    L. E. Seitz, W. J. Suling, and R. C. Reynolds, J. Med. Chem., 45, 5604 (2002).CrossRefGoogle Scholar
  13. 13.
    M. Dolezal, L. Palek, J. Vinsova, V. Buchta, J. Jampilek, and K. Kralova, Molecules, 11, 242 (2006).CrossRefGoogle Scholar
  14. 14.
    L. Palek, J. Dvorák, M. Svobodová, V. Buchta, J. Jampilek, and M. Dolezal, Arch. Pharm. (Weinheim), 341, 61 (2008).CrossRefGoogle Scholar
  15. 15.
    O. Zimhony, C. Vilchéze, M. Arai, J. T. Welch, and W. R. Jacobs, Antimicrob. Agents Chemother., 51, 752 (2007).CrossRefGoogle Scholar
  16. 16. TAACF Assay Results on Publically Available Compounds.
  17. 17.
    I. V. Ukrainets, E. V. Mospanova, and L. V. Sidorenko, Khim. Geterotsikl. Soedin., 1023 (2007). [Chem. Heterocycl. Comp., 43, 863 (2007)].Google Scholar
  18. 18.
    I. V. Ukrainets, A. A. Tkach, L. A. Grinevich, A. V. Turov, and O. V. Bevz, Khim. Geterotsikl. Soedin., 718 (2009). [Chem. Heterocycl. Comp., 45, 567 (2009)].Google Scholar
  19. 19.
    A. E. A. Porter in: A. R. Katritzky and C. W. Rees (editors), Comprehensive Heterocyclic Chemistry on CD-ROM: 7-Volume Set, Elsevier, Vol. 3, Oxford (1997), p. 157.Google Scholar
  20. 20.
    H.-B. Burgi and J. D. Dunitz, Structure Сorrelation, Vol. 2, VCH, Weinheim (1994), p. 741.CrossRefGoogle Scholar
  21. 21.
    Yu. V. Zefirov, Kristallografiya, 42, 936 (1997).Google Scholar
  22. 22.
    I. V. Ukrainets, L. V. Sidorenko, S. V. Slobodzian, V. B. Rybakov, and V. V. Chernyshev, Khim. Geterotsikl. Soedin., 1362 (2005). [Chem. Heterocycl. Comp., 41, 1158 (2005)].Google Scholar
  23. 23.
    I. V. Ukrainets, E. V. Kolesnik, L. V. Sidorenko, O. V. Gorokhova, and A. V. Turov, Khim. Geterotsikl. Soedin., 874 (2006). [Chem. Heterocycl. Comp., 42, 765 (2006)].Google Scholar
  24. 24.
    I. V. Ukrainets, V. V. Kravtsova, A. A. Tkach, and V. B. Rybakov, Khim. Geterotsikl. Soedin., 875 (2009). [Chem. Heterocycl. Comp., 45, 698 (2009)].Google Scholar
  25. 25.
    S. V. Shishkina, O. V. Shishkin, I. V. Ukrainets, N. L. Bereznyakova, and A. A. Davidenko, Acta Crystallogr., E64, o1031 (2008).Google Scholar
  26. 26.
    L. B. Heifets, in: L. B. Heifets (editor), Drug Susceptibility in the Chemotherapy of Mycobacterial Infections, CRC Press, Boca Raton (1991), p. 89.Google Scholar
  27. 27.
    C. B. Inderleid and K. A. Nash, in: V. Lorian (editor), Antibiotics in Laboratory Medicine, Williams and Wilkins, Baltimore (1996), p. 127.Google Scholar
  28. 28.
    G. M. Sheldrick, SHELXTL PLUS. PC Version. A System of Computer Programs for the Determination of Crystal Structure from X-ray Diffraction Data. Rev. 5.1 (1998).Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2009

Authors and Affiliations

  • I. V. Ukrainets
    • 1
    Email author
  • L. A. Grinevich
    • 1
  • A. A. Tkach
    • 1
  • O. V. Bevz
    • 1
  • S. V. Slobodzian
    • 2
  1. 1.National University of PharmacyKharkivUkraine
  2. 2.Northern Michigan UniversityMarquetteUSA

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