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Synthesis and Antidepressant Activity of 4-Alkyl-5-Bromo-2,4-Dihydro-2-(Thietan-3-YL)-1,2,4-Triazol-3-Ones

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Pharmaceutical Chemistry Journal Aims and scope

A series of 4-alkyl-5-bromo-2,4-dihydro-2-(thietan-3-yl)-1,2,4-triazol-3-ones (IIa-g) were synthesized by reacting 5-bromo-2,4-dihydro-2-(thietan-3-yl)-1,2,4-triazol-3-one (I) with alkyl halides and dimethyl sulfate. The structures of the synthesized compounds were confirmed by IR, PMR, and 13C NMR spectroscopic data. The antidepressant activity of the synthesized compounds in non-inbred male mice was investigated using tail-suspension and forced-swim tests. Compounds I and IIa,c,f,g after a single intraperitoneal injection produced antidepressant effects in screening tests and did not cause sedative and/or psychostimulatory effects in the open-field test. Compound I produced an antidepressant effect comparable to that of fluoxetine, had low toxicity (class IV toxicity), and was superior to fluoxetine in therapeutic index and strength of the antidepressant effect after a course of administration. The calculated physicochemical properties and toxic risks showed that all synthesized compounds complied fully with Lipinski’s rule of five. The calculated drug score and absence of predicted toxic risks for the most active compound I suggested that it was promising for creating a new pharmaceutical substance with antidepressant activity.

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References

  1. S. A. Alvano and L. M. Zieher, Pers. Med. Psychiatry, 19 – 20, 100042 (2019).

  2. T. Vos, S. S. Lim, C. Abbafati, et al., Lancet, 396(10258), 1204 – 1222 (2020).

    Article  Google Scholar 

  3. G. E. Mazo, A. O. Kibitov, G. V. Rukavishnikov, et al., Sotsial. Klin. Psikhiatr., 27(4), 70 – 80 (2017).

    Google Scholar 

  4. Y. Xu, C. Wang, J. Klabnik, et al., Curr Neuropharmacol., 12, No. 2, 108 – 119 (2014).

    Article  CAS  Google Scholar 

  5. R. Aggarwal and G. Sumran, Eur. J. Med. Chem., 205, 112652 (2020).

    Article  CAS  Google Scholar 

  6. A. Kleeman, J. Engel, B. Kutscher, et al., Pharmaceutical Substances: Syntheses, Patents, and Applications of the Most Relevant AIPs, 5th Ed., Thieme Medical Publ. Inc., New York (2009).

    Google Scholar 

  7. R. A. Bekker and Yu. V. Bykov, Psikhiatr. Psikhofarmakoter., 20(3 – 4), 51 – 62 (2018).

  8. J. Jaskowska, P. Zareba, P. Sliwa, et al., Molecules, 24(8), 1609 (2019).

    Article  Google Scholar 

  9. S. Wang, H. Liu, X. Wang, et al., Molecules, 24(10), 1857 (2019).

    Article  CAS  Google Scholar 

  10. 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).

  11. E. E. Klen, I. L. Nikitina, N. N. Makarova, et al., Khim.-farm. Zh., 50(10), 15 – 21 (2016); Pharm. Chem. J., 50(10), 642 – 648 (2017).

  12. F. A. Khaliullin, I. L. Nikitina, E. E. Klen, et al., Khim.-farm. Zh., 53(12), 8 – 15 (2019); Pharm. Chem. J., 53(12), 1106 – 1112 (2020).

  13. E. E. Klen, I. L. Nikitina, et al., RU Pat. 2,459,818 C1, Aug. 27, 2012; https: // new.fips.ru/registers-doc-view/fips_servlet? DB= RUPAT&DocNumber-0002459818&TypeFile=html.

  14. E. E. Klen, I. L. Nikitina, F. A. Khaliullin, et al., Vopr. Biol., Med. Farm. Khim., No. 7, 42 – 45 (2010).

  15. R. M. Silverstein, F. X. Webster, and D. J. Kiemle, Spectrometric Identification of Organic Compounds, John Wiley & Sons, Hoboken, NJ (2005) [Russian translation, Binom, Laboratoriya Znanii, Moscow (2011), pp. 263 – 264].

  16. Interstate Committee on Standardization, Metrology, and Certification, GOST 33215-2014, Guidelines for Accommodation and Care of Laboratory Animals. Rules for Equipment of Premises and Organization of Procedures, Standartinform, 2016; https: // allgosts.ru / 13 / 020 / gost 33215 – 2014.

  17. L. Steru, R. Chermat, B. Thierry, et al., Psychopharmacology (Berlin), 85(3), 367 – 370 (1985).

    Article  CAS  Google Scholar 

  18. E. V. Shchetinin, V. A. Baturin, E. B. Arushanyan, et al., Zh. Vyssh. Nervn. Deyat. im. I. P. Pavlova, 39(5), 958 – 964 (1989).

  19. S. C. Stanford, J. Psychopharmacol. Oxf. Engl., 21(2), 134 – 135 (2007).

    Google Scholar 

  20. Certificate of State Registration of a Computer Program, No. 2008610170 (Russia) (2008).

  21. J. T. Litchfield and F. T. Wilcoxon, J. Pharmacol. Exp. Ther., 96(2), 99 – 113 (1949).

    CAS  Google Scholar 

  22. V. B. Prozorovskii, Farmakol. Toksikol., 25(1), 115 – 119 (1962).

    CAS  PubMed  Google Scholar 

  23. R Core Team (2018). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria; https: // www. R-project.org/.

  24. H. Wickham, ggplot2: Elegant Graphics for Data Analysis, Springer-Verlag, New York (2016).

  25. K. K. Sidorov, in: Toxicology of New Industrial Substances [in Russian], No. 8, Meditsina, Moscow (1973), pp. 47 – 51.

  26. C. A. Lipinski, J. Pharmacol. Toxicol. Methods, 44(1), 235 – 249 (2000).

    Article  CAS  Google Scholar 

  27. C. A. Lipinski, F. Lombardo, B. W. Dominy, et al., Adv. Drug Deliv. Rev., 46(1), 3 – 26 (2001).

    Article  CAS  Google Scholar 

  28. T. Sander, J. Freyss, M. von Korff, et al., J. Chem. Inf. Model., 55(2), 460 – 473 (2015).

    Article  CAS  Google Scholar 

  29. T. Sander, Molecular Properties Prediction – Osiris Property Explorer; https: // www.organic-chemistry.org / prog / peo / .

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Authors and Affiliations

  1. Bashkir State Medical University, 3 Lenina St, Ufa, Bashkortostan, 450008, Russia

    F. A. Khaliullin, I. L. Nikitina, E. E. Klen, A. F. Miftakhova, N. N. Makarova & A. G. Gilmanova

  2. BIOCAD Biopharmaceutical Co., 34-A Svyazi St., Strelna, St. Petersburg, 198515, Russia

    R. A. Gabidullin

Authors
  1. F. A. Khaliullin
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  2. I. L. Nikitina
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  3. E. E. Klen
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  4. A. F. Miftakhova
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  5. N. N. Makarova
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  6. R. A. Gabidullin
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  7. A. G. Gilmanova
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Correspondence to F. A. Khaliullin.

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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 55, No. 2, pp. 13 – 19, February, 2021.

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Khaliullin, F.A., Nikitina, I.L., Klen, E.E. et al. Synthesis and Antidepressant Activity of 4-Alkyl-5-Bromo-2,4-Dihydro-2-(Thietan-3-YL)-1,2,4-Triazol-3-Ones. Pharm Chem J 55, 123–129 (2021). https://doi.org/10.1007/s11094-021-02394-0

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  • DOI: https://doi.org/10.1007/s11094-021-02394-0

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