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

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. A series of 5‐substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity and neurotoxicity. The most active compound 3c showed high protection against 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. The protective index of compound 3c (TD50/ED50 = 23.4) is comparable to those of reference antiepileptic drugs.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research