Design and Synthesis of 5-Substituted Benzo[d][1,3]dioxole Derivatives as Potent Anticonvulsant Agents

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• 作者：Shiyang Dong ; Tiantian Wang ; Chundi Hu ; Xiaodong Chen ; Yi Jin and Zengtao Wang
• 刊名：Archiv der Pharmazie
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：350
• 期：2
• 全文大小：616K
• ISSN：1521-4184

文摘

A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d–f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED₅₀ value of 9.8 mg/kg and a TD₅₀ value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD₅₀/ED₅₀) of 23.4 comparable to those of reference antiepileptic drugs.