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Design and Synthesis of 5‐Substituted Benzo[ d ][1,3]dioxole Derivatives as Potent Anticonvulsant Agents
Author(s) -
Dong Shiyang,
Wang Tiantian,
Hu Chundi,
Chen Xiaodong,
Jin Yi,
Wang Zengtao
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600274
Subject(s) - anticonvulsant , ed50 , chemistry , neurotoxicity , pharmacology , intraperitoneal injection , stereochemistry , toxicity , epilepsy , biochemistry , medicine , receptor , psychology , organic chemistry , neuroscience
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 ED 50 value of 9.8 mg/kg and a TD 50 value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD 50 /ED 50 ) of 23.4 comparable to those of reference antiepileptic drugs.