Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Synthesis and Analysis of Anticonvulsant Activities of New 4-[2-(4- alkoxybenzylamino)ethyl]-2H-1,2,4-triazol-3(4H)-one Derivatives

Author(s): Qing-Kun Shen, Shi-Ben Wang, Guo-Hua Gong, Xiu-Mei Yin, Zhe-Shan Quan.

Graphical Abstract:


Abstract:

The present study involved the design and synthesis of new substituted 4-[2-(4- alkoxybenzylamino) ethyl]-2H-1,2,4-triazol-3(4H)-one derivatives (8a-w) starting from 1,2- ethanediamine. The final compounds were screened for their in vivo anticonvulsant activities and neurotoxicities by maximal electroshock (MES) and rotarod tests, respectively. Among the compounds studied, 4-[2-(4-butoxybenzylamino)ethyl]-2H-1,2,4-triazol-3(4H)-one hydrochloride (8b) was found by intraperitoneal administration in mice to be the most potent compound with a median effective dose (ED50) value of 33.2 mg/kg and a high protective index (PI) value of 11.4. Compound 8b showed significant oral activity against MES-induced seizures in mice with an ED50 value of 83.1 mg/kg and a PI of 18.1. The results demonstrated that compound 8b possessed better anticonvulsant activity and higher safety than the marketed drug carbamazepine.

Keywords: Anticonvulsant activity, carbamazepine, maximal electroshock test, rotarod test, synthesis, triazolone.

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Article Details

VOLUME: 12
ISSUE: 5
Year: 2015
Page: [430 - 438]
Pages: 9
DOI: 10.2174/1570180812666141111235746
Price: $58