کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1398882 | 1501130 | 2014 | 10 صفحه PDF | دانلود رایگان |
• 4-Alkyl-1,2,4-triazole-3-thiones were designed and synthesized.
• Methylene linker significantly affected the anticonvulsant activity in the MES test.
• The obtained compounds didn't interact with GABAA receptor.
A series of 4-alkyl-5-(3-chlorobenzyl/2,3-dichlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (1a–14a) were designed, synthesized and screened for their anticonvulsant properties. Moreover, the acute adverse-effect profile of the active compounds (1a–7a, 12a) with respect to impairment of motor performance was evaluated in the chimney test. Among 4-alkyl-5-(3-chlorobenzyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones, ethyl, butyl, pentyl, hexyl, and heptyl derivatives administered intraperitoneally in a dose of 300 mg/kg protected 100% of the tested animals at four pretreatment times (i.e., 15, 30, 60, 120 min). Taking into account the median effective and toxic doses as well as the time-course profile of anticonvulsant activity, 5-(3-chlorobenzyl)-4-hexyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (4a) was proposed as the best tolerated and the most promising potential drug candidate. Finally, a radioligand binding assay was used to check whether the anticonvulsant activity of 4-alkyl-1,2,4-triazole-3-thiones was a result of their interactions (direct or allosteric) with GABAA receptor complex and/or their affinity to benzodiazepine (BDZ) binding sites.
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Journal: European Journal of Medicinal Chemistry - Volume 86, 30 October 2014, Pages 690–699