Pharmaceutical Chemistry Journal

, Volume 50, Issue 12, pp 775–780 | Cite as

Prediction and Study of Anticonvulsant Properties of Benzimidazole Derivatives

  • P. M. Vasil’ev
  • K. Yu. Kalitin
  • A. A. Spasov
  • O. Yu. Grechko
  • V. V. Poroikov
  • D. A. Filimonov
  • V. A. Anisimova
SEARCH FOR NEW DRUGS

Anticonvulsive activities of some condensed imidazo[1,2-a]benzimidazole derivatives were predicted using PASS software. Benzimidazoles as a class showed promise as sources of anticonvulsants. Several compounds demonstrated various levels of anticonvulsive activity in the corazole-induced seizure model (75 mg/kg, s.c.). The most promising compounds (laboratory codes RU-1205, RU-285, RU-1204, and RU-1203) at a dose of 10 mg/kg (i.p.) showed high levels of anticonvulsive activity comparable with that of reference valproic acid (130 mg/kg, i.p.) at a molar ratio of ~1:30. The Free—Wilson model was used to describe quantitative structure—activity relationships in order to evaluate contributions of substituents or structural fragments to the anticonvulsive activity of the parent structure. Four pharmacophore patterns that favored high anticonvulsive activity among imidazo[1, 2-a]benzimidazole derivatives were found using IT Microcosm.

Keywords

benzimidazole corazole screening anticonvulsive activity anticonvulsants valproic acid epilepsy PASS system IT Microcosm Free—Wilson method pharmacophores 

Notes

Acknowledgments

The synthesis of the chemical compounds was sponsored by the project part of a state task for scientific activity (No. 4.196.2014/K) and was performed using equipment at the Molecular Spectroscopy CCU, SFU. Activities were predicted using PASS within the framework of the Basic Research Program of State Academies of Sciences for 2014 – 2020 (Topic No. 3).

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • P. M. Vasil’ev
    • 1
  • K. Yu. Kalitin
    • 1
  • A. A. Spasov
    • 1
    • 4
  • O. Yu. Grechko
    • 1
  • V. V. Poroikov
    • 2
  • D. A. Filimonov
    • 2
  • V. A. Anisimova
    • 3
  1. 1.Volgograd State Medical UniversityVolgogradRussia
  2. 2.V. N. Orekhovich Institute of Biomedical ChemistryMoscowRussia
  3. 3.Institute of Physical and Organic ChemistrySouthern Federal UniversityRostov-on-DonRussia
  4. 4.Volgograd Medical Scientific CenterVolgogradRussia

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