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Pharmaceutical Chemistry Journal

, Volume 52, Issue 3, pp 198–204 | Cite as

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

  • S. S. Zykova
  • N. M. Igidov
  • A. V. Zakhmatov
  • M. A. Kiselev
  • A. R. Galembikova
  • R. R. Khusnutdinov
  • P. D. Dunaev
  • S. V. Boichuk
  • I. N. Chernov
  • I. A. Rodin
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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.

Keywords

2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamides acute toxicity cytotoxicity gastrointestinal stromal tumors (GISTs) chemotherapeutics, chemoresistance 

Notes

Acknowledgments

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

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • S. S. Zykova
    • 1
  • N. M. Igidov
    • 2
  • A. V. Zakhmatov
    • 2
  • M. A. Kiselev
    • 2
  • A. R. Galembikova
    • 3
  • R. R. Khusnutdinov
    • 3
  • P. D. Dunaev
    • 3
  • S. V. Boichuk
    • 3
  • I. N. Chernov
    • 4
  • I. A. Rodin
    • 5
  1. 1.Perm Federal Penitentiary Service InstitutePermRussia
  2. 2.Perm State Pharmaceutical AcademyPermRussia
  3. 3.Kazan State Medical UniversityKazanRussia
  4. 4.Research Institute of ChemistryN. I. Lobachevsky State University of Nizhny NovgorodNizhny NovgorodRussia
  5. 5.I. T. Trubilin Kuban State Agrarian UniversityKrasnodarRussia

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