Synthesis and Antidepressant Activity of 4-Alkyl-5-Bromo-2,4-Dihydro-2-(Thietan-3-YL)-1,2,4-Triazol-3-Ones
| Autor: | I. L. Nikitina, F. A. Khaliullin, N. N. Makarova, A. F. Miftakhova, E. E. Klen, A. G. Gilmanova, R. A. Gabidullin |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Fluoxetine 010405 organic chemistry medicine.drug_class Chemistry medicine.medical_treatment Intraperitoneal injection 01 natural sciences Medicinal chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Dimethyl sulfate chemistry.chemical_compound Therapeutic index Sedative Drug Discovery Toxicity medicine Lipinski's rule of five Alkyl medicine.drug |
| Zdroj: | Pharmaceutical Chemistry Journal. 55:123-129 |
| ISSN: | 1573-9031 0091-150X |
| DOI: | 10.1007/s11094-021-02394-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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