Skip to main content
SpringerLink
Log in

Synthesis and Biological Activity of 2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1h-pyrrole-3-carboxamides

  • SEARCH FOR NEW DRUGS
  • Published:
Pharmaceutical Chemistry Journal Aims and scope

A series of new 2-aminopyrrole derivatives [2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamides IIa-h] were synthesized via the reaction of 4-arylamino-2-tert-butyl-2,5-dihydro-5-oxofuran-2-ylacetates (Ia-h) with 2-cyano-N-(thiazol-2-yl)acetamide in the presence of Et3N. Studies of the biological activity of the synthesized compounds found that they possessed low toxicity and that 2-amino-1-(2-bromophenyl)-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamide (IIb) and 2-amino-1-(2,4-dichlorophenyl)-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamide (IIg) exhibited radical-binding activity greater than that of trolox and cytotoxic activity against gastrointestinal stromal tumor (GIST) cells, including those resistant to the target drug imatinib (Glivec). The cytotoxic activity of the synthesized compounds was comparable with that of doxorubicin chemotherapeutics and exceeded significantly those of etoposide, paclitaxel, and hydroxyurea. Apossible molecular mechanism of action of the synthesized compounds might be their ability to disrupt cell division and induce selective accumulation of M-phase cells with subsequent death by a mitotic catastrophe pathway.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  1. G. D. Demetri, M. von Mehren, C. D. Blanke, et al., N. Engl. J. Med., 347, 472 – 480 (2002).

    Article  PubMed  CAS  Google Scholar 

  2. J. Verweij, P. G. Casali, J. Zalcberg, et al., Lancet, 364, 1127 – 1133 (2004).

    Article  PubMed  CAS  Google Scholar 

  3. A. W. Gramza, C. L. Corless, and M. C. Heinrich, Clin. Cancer Res., 15, 7510 – 7518 (2009).

    Article  PubMed  CAS  Google Scholar 

  4. T. Taguchi, H. Sonobe, S. Toyonaga, I. Yamasaki, et al., Lab. Invest., 82, 663 – 665 (2002).

    Article  PubMed  Google Scholar 

  5. S. Boichuk, D. J. Lee, K. R. Mehalek, et al., Cancer Res., 74(4), 1200 – 1213 (2014).

    Article  PubMed  CAS  Google Scholar 

  6. S. S. Zykova, A. R. Galembikova, B. R. Ramazanov, et al., Khim.-farm. Zh., 49(12), 19 – 23 (2015); S. S. Zykova, A. R. Galembikova, B. R. Ramazanov, et al., Khim.-farm. Zh., 49(12), 817 – 820 (2016).

  7. S. Boichuk, A. Galembikova, S. Zykova, B. Ramazanov, et al., Anti-Cancer Drugs, 27(7), 620 – 634 (2016).

    Article  PubMed  CAS  Google Scholar 

  8. S. S. Kharitonova, N. M. Igidov, A. V. Zakhmatov, and A. E. Rubtsov, Zh. Org. Khim., 49(2), 252 (2013); S. S. Kharitonova, N. M. Igidov, A. V. Zakhmatov, and A. E. Rubtsov, Russ. J. Org. Chem., 49, 243 (2013).

  9. S. S. Zykova, A. A. Darovskikh, T. F. Odegova, et al., Khim.- farm. Zh., 49(10), 15 – 18 (2015); S. S. Zykova, A. A. Darovskikh, T. F. Odegova, et al., Pharm. Chem. J., 49(10), 657 – 660 (2016).

  10. S. S. Zykova, S. V. Boichuk, A. R. Galembikova, et al., Tsitologiya, 56(6), 439 – 442 (2014).

    CAS  Google Scholar 

  11. S. S. Zykova and S. V. Boichuk, in: Proceedings of the XVIIIth International Scientific Conference “Oncology – XXIst Century” [in Russian], Brussels, Belgium (2013), pp. 75 – 78.

  12. N. M. Igidov, A. V. Zakhmatov, and A. E. Rubtsov, Zh. Org. Khim., 52(7), 981 (2016).

    Google Scholar 

  13. A. V. Tyuneva, N. M. Igidov, and N. N. Koryagina, Zh. Org. Khim., 47, 266 (2011); A. V. Tyuneva, N. M. Igidov, and N. N. Koryagina, Russ. J. Org. Chem., 47, 258 (2011).

  14. P. Molyneux, Songklanakarin J. Sci. Technol., 26, No. 2, 211 – 219 (2004).

    CAS  Google Scholar 

  15. S. S. Zykova, S. V. Boichuk, A. R. Galembikova, et al., RU Pat. No. 2,605,091, Dec. 10, 2016; “2-Amino-1-aryl-5-(3,3- dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1Hpyrrole-3-carboxamides, exhibiting antitumour and antiradical activity, synthesis method thereof and pharmaceutical composition based thereon”.

  16. I. V. Berezovskaya, Khim.-farm. Zh., 37(3), 32 – 34 (2003).

    Google Scholar 

Download references

Acknowledgments

The research was financially supported by the Russian Science Foundation (RSF) Grant No. 14-15-00342.

Author information

Authors and Affiliations

  1. Perm Federal Penitentiary Service Institute, 125 Karpinskogo St., Perm, 614012, Russia

    S. S. Zykova

  2. Perm State Pharmaceutical Academy, 2 Polevaya St., Perm, 614099, Russia

    N. M. Igidov, A. V. Zakhmatov & M. A. Kiselev

  3. Kazan State Medical University, 49 Butlerova St., Kazan, Tatarstan, 420012, Russia

    A. R. Galembikova, R. R. Khusnutdinov, P. D. Dunaev & S. V. Boichuk

  4. Research Institute of Chemistry, N. I. Lobachevsky State University of Nizhny Novgorod, 23/5 Prosp. Gagarina, Nizhny Novgorod, 603950, Russia

    I. N. Chernov

  5. I. T. Trubilin Kuban State Agrarian University, 13 Kalinina St, Krasnodar, 350044, Russia

    I. A. Rodin

Authors
  1. S. S. Zykova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. M. Igidov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Zakhmatov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. A. Kiselev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. R. Galembikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. R. Khusnutdinov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. D. Dunaev
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. V. Boichuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. I. N. Chernov
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. I. A. Rodin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. S. Zykova.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 52, No. 3, pp. 10 – 16, March, 2018.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zykova, S.S., Igidov, N.M., Zakhmatov, A.V. et al. Synthesis and Biological Activity of 2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1h-pyrrole-3-carboxamides. Pharm Chem J 52, 198–204 (2018). https://doi.org/10.1007/s11094-018-1790-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-018-1790-9

Keywords

Search

Navigation