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

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 H 2...

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Published inPharmaceutical chemistry journal Vol. 50; no. 10; pp. 642 - 648
Main Authors Klen, E. É., Nikitina, I. L., Makarova, N. N., Miftakhova, A. F., Ivanova, O. A., Khaliullin, F. A., Alekhin, E. K.
Format Journal Article
LanguageEnglish
Published New York Springer US 2017
Springer
Subjects
Antidepressants
Biphenyl (Compound)
Medicine
Organic Chemistry
Pharmacology/Toxicology
Pharmacy
prediction
1,2,4-triazoles
thietanes
Lipinski’s rule of five
antidepressant activity
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Summary: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 H 2 O 2 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.
ISSN:0091-150X
1573-9031
DOI:10.1007/s11094-017-1506-6