Design, synthesis and evaluation of 5-substituted 1-H-tetrazoles as potent anticonvulsant agents
Ai-Mei Liao1,2, Tiantian Wang3,4, Bangrong Cai1
1Research Institute of Drug Development, College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
Abstract:
A series of 5-substituted 1-H-tetrazoles were designed and synthesized as potent anticonvulsant agents. Their preliminary anticonvulsant activities were evaluated using maximal electroshock and subcutaneous pentylenetetrazole (scPTZ) seizure tests. Neurotoxicity was determined using rotarod test. The results indicated that the compound 2j in scPTZ model exhibited the ED50 values of 83.3 mg/kg, superior to the standard drug ethosuximide with the maximum activity. In addition, compound 2k showed the most potent activity in MES model with ED50 value of 9.6 mg/kg and TD50 value of 189.5 mg/kg after intraperitoneal injection in mice, and displayed a high protective index (TD50/ED50) of 19.7 compared to reference antiepileptic drugs.
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