title: Design, synthesis and evaluation of 5-substituted 1-H-tetrazoles as potent anticonvulsant agents.
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 ED50values 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 ED50value of 9.6 mg/kg and TD50value 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.
authors.affiliation: Research Institute of Drug Development, College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju, 61186, Republic of Korea.|School of life Science, Hefei Normal University, Hefei, 230601, China.
authors.forename: Ai-Mei
authors.initials: AM
authors.lastname: Liao
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, 330004, China.|The National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, 330006, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Research Institute of Drug Development, College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
authors.forename: Bangrong
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, 330004, China.|The National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, 330006, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Research Institute of Drug Development, College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Cheon
authors.affiliation: Research Institute of Drug Development, College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju, 61186, Republic of Korea. cchun1130@jnu.ac.kr.
authors.forename: ChangJu
authors.initials: C
authors.lastname: Chun
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, 330004, China. zengtaowang@126.com.
authors.forename: Zengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000008:administration & dosage; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D013777:Tetrazoles; C045574:1H-tetrazole; D010433:Pentylenetetrazole
keywords: 5-Substituted 1-H-tetrazoles; Anticonvulsant; Synthesis