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.
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References
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.pdf
V. S. Yastrebov, I. A. Mitikhina, V. G. Mitikhin, et al., Zh. Nevrol. Psikhiatr. im. S. S. Korsakova, No. 2, 4 – 13 (2012).
J. C. Fournier, R. J. DeRubeis, S. D. Hollon Dimidjian, et al., J. Am. Med. Assoc., 303(1), 47 – 53 (2010).
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
E. E. Klen, N. N. Makarova, F. A. Khaliullin, et al., Bashk. Khim. Zh., 15(4), 112 – 114 (2008).
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).
E. E. Klen, F. A. Khaliullin, and N. N. Makarova, Zh. Org. Khim., 44(11), 1729 – 1731 (2008).
E. Block, in: Comprehensive Heterocyclic Chemistry, Vol. 7, A. R. Katritzky and C. W. Rees (eds.), Oxford, New York (1997), pp. 403 – 448.
E. V. Shchetinin, V. A. Baturin, E. B. Arushanyan, et al., Zh. Vyssh. Nervn. Deyat., No. 5, 958 – 964 (1989).
D. C. Young, Computational Drug Design, John Wiley & Sons Inc., Hoboken, New Jersey (2009).
C. A. Lipinsky, F. Lombardo, B. W. Dominy, and P. J. Feeney, Adv. Drug Delivery Rev., 46, 3 – 26 (2001).
C. A. Lipinsky, J. Pharmacol. Toxicol. Methods, 44, 235 – 249 (2000).
P. Ertl, B. Rohde, and P. Selzer, J. Med. Chem., 43(20), 3714 – 3717 (2000).
Y. H. Zhao, M. H. Abraham, J. Le, A. Hersey, et al., Pharm. Res., 19(10), 1446 – 1457 (2002).
R. D. Porsolt, M. L. Pichon, and M. Jalfre, Nature, 266, 730 – 732 (1977).
L. Steru, R. Chermat, B. Thierry, et al., Psychopharmacology (Berlin, Ger.), 85(3), 367 – 370 (1985).
R. A. Gabidullin, O. A. Ivanova, I. L. Nikitina, et al., State Registration Certificate for Computer Program No. 2008610170, Moscow (2008).
S. Glantz, Primer of Biostatistics, McGraw-Hill, New York (1997) [Russian translation, Praktika, Moscow (1998)].
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 50, No. 10, pp. 15 – 21, October, 2016.
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Klen, E.É., Nikitina, I.L., Makarova, N.N. et al. 3-Substituted Thietane-1,1-Dioxides: Synthesis, Antidepressant Activity, and in Silico Prediction of Their Pharmacokinetic and Toxicological Properties. Pharm Chem J 50, 642–648 (2017). https://doi.org/10.1007/s11094-017-1506-6
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DOI: https://doi.org/10.1007/s11094-017-1506-6