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Molecules 2018, 23(4), 756;

Synthesis and Evaluation of the Anticonvulsant Activities of 4-(2-(Alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones

Medical College, Jinggangshan University, No. 28, Xueyuan Road, Ji’an 343009, Jiangxi, China
Siping Institute of Food and Drug Control, No. 357, Nanhu Road, Sipin 136000, Jilin, China
Author to whom correspondence should be addressed.
Received: 1 March 2018 / Revised: 22 March 2018 / Accepted: 23 March 2018 / Published: 25 March 2018
(This article belongs to the Section Medicinal Chemistry)
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In this study, a novel series of 4-(2-(alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (4am) was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The neurotoxicity of these compounds was evaluated using the rotarod neurotoxicity test. The majority of compounds showed anti-MES activities at 100 or 300 mg/kg. Compound 4g was considered to be the most promising, based on its potency against MES- and PTZ-induced seizures with ED50 values of 23.7 and 18.9 mg/kg, respectively. The TD50 value of 4g was 284.0 mg/kg, which resulted in a higher protective index (PI = TD50/ED50) value than that of carbamazepine and valproate. In an ELISA test, compound 4g significantly increased the γ-aminobutyric acid (GABA) content in mouse brain. In addition, pretreatment with thiosemicarbazide (an inhibitor of the GABA synthesizing enzyme) significantly decreased the activity of 4g in the MES model, which suggests that the mechanism through which compound 4g elicits its anticonvulsive action is at least in part through increasing the GABA level in the brain. View Full-Text
Keywords: anticonvulsant; maximal electroshock; pentylenetetrazole; benzoxazole; triazolone anticonvulsant; maximal electroshock; pentylenetetrazole; benzoxazole; triazolone

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Song, M.-X.; Wang, Z.-Y.; He, S.-H.; Yu, S.-W.; Chen, S.-L.; Guo, D.-F.; Zhao, W.-H.; Deng, X.-Q. Synthesis and Evaluation of the Anticonvulsant Activities of 4-(2-(Alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones. Molecules 2018, 23, 756.

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