Advertisement

Pharmaceutical Chemistry Journal

, Volume 50, Issue 10, pp 642–648 | Cite as

3-Substituted Thietane-1,1-Dioxides: Synthesis, Antidepressant Activity, and in Silico Prediction of Their Pharmacokinetic and Toxicological Properties

  • E. É. Klen
  • I. L. Nikitina
  • N. N. Makarova
  • A. F. Miftakhova
  • O. A. Ivanova
  • F. A. Khaliullin
  • E. K. Alekhin
Article
  • 88 Downloads

3-Aryloxy- and 3-phenylsulfanylthietane-1,1-dioxides were synthesized by reacting 3,5-dibromo-1-(1,1-dioxothietan-3-yl)-1,2,4-triazole with sodium phenolates and thiophenolate. The 5-aryloxy- and 5-arenesulfonyl-3-bromo-1-(1,1-dioxothietan-3-yl)-1,2,4-triazoles were synthesized via oxidation by H2O2 of 5-aryloxy- and 5-phenylsulfanyl-3-bromo-1,2,4-triazoles containing thietane or thietane oxide rings. The 3-substituted thietane-1,1-dioxide IId (2 and 20 mg/kg) displayed antidepressant properties in tail-suspension (TST) and forced-swim tests (FST) that were comparable with those of imipramine. Low toxicity risks (mutagenicity, tumorigenicity, irritation, reproductive toxicity) and satisfactory pharmacokinetic characteristics (correspondence to Lipinski’s rule of five) were predicted (Osiris Property Explorer, Molinspiration) for it.

Keywords

thietanes 1,2,4-triazoles antidepressant activity prediction Lipinski’s rule of five 

References

  1. 1.
    Global Burden of Disease: Generating Evidence, Guiding Policy, Europe and Central Asia Regional Edition, Human Development Network, World Bank, Institute for Health Metrics and Evaluation, Seattle, WA, 2013; http: // www-wds.worldbank. org / external / default / WDSContentServer / IW3P / IB / 2013 / 09 / 03 / 000456288 20130903105621 / Rendered / PDF / 808480PUB0RUSS0Box0379820B00PUBLIC0.pdfGoogle Scholar
  2. 2.
    V. S. Yastrebov, I. A. Mitikhina, V. G. Mitikhin, et al., Zh. Nevrol. Psikhiatr. im. S. S. Korsakova, No. 2, 4 – 13 (2012).Google Scholar
  3. 3.
    J. C. Fournier, R. J. DeRubeis, S. D. Hollon Dimidjian, et al., J. Am. Med. Assoc., 303(1), 47 – 53 (2010).CrossRefGoogle Scholar
  4. 4.
    O. A. Ivanova, I. L. Nikitina, et al., RU Pat. 2,424,799, Jul. 27, 2011; Byull. Izobret., No. 21 (2011); http: // www1.fips.ru / Archive / PAT / 2011FULL / 2011.07.21 / DOC / RUNWC1 / 000 / 000 / 002 / 424 / 799 / document.pdf
  5. 5.
    E. E. Klen, N. N. Makarova, F. A. Khaliullin, et al., Bashk. Khim. Zh., 15(4), 112 – 114 (2008).Google Scholar
  6. 6.
    I. L. Nikitina, R. A. Gabidullin, E. E. Klen, et al., Khim.-farm. Zh., 46(4), 17 – 22 (2012); Pharm. Chem. J., 46(4), 213 – 218 (2012).Google Scholar
  7. 7.
    E. E. Klen, F. A. Khaliullin, and N. N. Makarova, Zh. Org. Khim., 44(11), 1729 – 1731 (2008).Google Scholar
  8. 8.
    E. Block, in: Comprehensive Heterocyclic Chemistry, Vol. 7, A. R. Katritzky and C. W. Rees (eds.), Oxford, New York (1997), pp. 403 – 448.Google Scholar
  9. 9.
    E. V. Shchetinin, V. A. Baturin, E. B. Arushanyan, et al., Zh. Vyssh. Nervn. Deyat., No. 5, 958 – 964 (1989).Google Scholar
  10. 10.
    D. C. Young, Computational Drug Design, John Wiley & Sons Inc., Hoboken, New Jersey (2009).CrossRefGoogle Scholar
  11. 11.
    C. A. Lipinsky, F. Lombardo, B. W. Dominy, and P. J. Feeney, Adv. Drug Delivery Rev., 46, 3 – 26 (2001).CrossRefGoogle Scholar
  12. 12.
    C. A. Lipinsky, J. Pharmacol. Toxicol. Methods, 44, 235 – 249 (2000).CrossRefGoogle Scholar
  13. 13.
    P. Ertl, B. Rohde, and P. Selzer, J. Med. Chem., 43(20), 3714 – 3717 (2000).CrossRefPubMedGoogle Scholar
  14. 14.
  15. 15.
    Y. H. Zhao, M. H. Abraham, J. Le, A. Hersey, et al., Pharm. Res., 19(10), 1446 – 1457 (2002).CrossRefPubMedGoogle Scholar
  16. 16.
  17. 17.
    R. D. Porsolt, M. L. Pichon, and M. Jalfre, Nature, 266, 730 – 732 (1977).CrossRefPubMedGoogle Scholar
  18. 18.
    L. Steru, R. Chermat, B. Thierry, et al., Psychopharmacology (Berlin, Ger.), 85(3), 367 – 370 (1985).Google Scholar
  19. 19.
    R. A. Gabidullin, O. A. Ivanova, I. L. Nikitina, et al., State Registration Certificate for Computer Program No. 2008610170, Moscow (2008).Google Scholar
  20. 20.
    S. Glantz, Primer of Biostatistics, McGraw-Hill, New York (1997) [Russian translation, Praktika, Moscow (1998)].Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • E. É. Klen
    • 1
  • I. L. Nikitina
    • 1
  • N. N. Makarova
    • 1
  • A. F. Miftakhova
    • 1
  • O. A. Ivanova
    • 1
  • F. A. Khaliullin
    • 1
  • E. K. Alekhin
    • 1
  1. 1.Bashkir State Medical UniversityUfaRussia

Personalised recommendations