3-Substituted Thietane-1,1-Dioxides: Synthesis, Antidepressant Activity, and in Silico Prediction of Their Pharmacokinetic and Toxicological Properties
- Autores: Klen E.1, Nikitina I.1, Makarova N.1, Miftakhova A.1, Ivanova O.1, Khaliullin F.1, Alekhin E.1
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Afiliações:
- Bashkir State Medical University
- Edição: Volume 50, Nº 10 (2017)
- Páginas: 642-648
- Seção: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/244453
- DOI: https://doi.org/10.1007/s11094-017-1506-6
- ID: 244453
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Resumo
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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Sobre autores
E. Klen
Bashkir State Medical University
Email: khaliullin.ufa@yahoo.com
Rússia, 3 Lenina St, Ufa, 450000
I. Nikitina
Bashkir State Medical University
Email: khaliullin.ufa@yahoo.com
Rússia, 3 Lenina St, Ufa, 450000
N. Makarova
Bashkir State Medical University
Email: khaliullin.ufa@yahoo.com
Rússia, 3 Lenina St, Ufa, 450000
A. Miftakhova
Bashkir State Medical University
Email: khaliullin.ufa@yahoo.com
Rússia, 3 Lenina St, Ufa, 450000
O. Ivanova
Bashkir State Medical University
Email: khaliullin.ufa@yahoo.com
Rússia, 3 Lenina St, Ufa, 450000
F. Khaliullin
Bashkir State Medical University
Autor responsável pela correspondência
Email: khaliullin.ufa@yahoo.com
Rússia, 3 Lenina St, Ufa, 450000
E. Alekhin
Bashkir State Medical University
Email: khaliullin.ufa@yahoo.com
Rússia, 3 Lenina St, Ufa, 450000