Zhang Lei, Guan Li-Ping, Sun Xian-Yu, Wei Cheng-Xi, Chai Kyu-Yun, Quan Zhe-Shan
Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, Jilin Province, China.
Chem Biol Drug Des. 2009 Mar;73(3):313-9. doi: 10.1111/j.1747-0285.2009.00776.x.
A new series of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines (3a-3v) were synthesized and their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock test and the rotarod test respectively. Significant anticonvulsant activity was displayed by a number of compounds. The most promising compounds 6-(4-chlorobenzyloxy)-[1,2,4]triazolo[3,4-a]phthalazine (3f) and 6-heptyloxy-[1,2,4]triazolo[3,4-a]phthalazine (3s) showed a median effective dose of 7.1 and 11.0 mg/kg, and had protective index value of 5.2 and 8.0 respectively. The two compounds were further found to have potent activity against seizures induced by pentylenetetrazole, isoniazid, thiosemicarbazide, 3-mercaptopropionic acid but not seizures induced by strychnine, indicating that the two compounds might function by enhancing gamma-aminobutyric acid neurotransmission.
合成了一系列新的6-烷氧基-[1,2,4]三唑并[3,4-a]酞嗪类化合物（3a - 3v），并分别通过最大电休克试验和转棒试验评估了它们的抗惊厥活性和神经毒性。许多化合物表现出显著的抗惊厥活性。最有前景的化合物6-(4-氯苄氧基)-[1,2,4]三唑并[3,4-a]酞嗪（3f）和6-庚氧基-[1,2,4]三唑并[3,4-a]酞嗪（3s）的半数有效剂量分别为7.1和11.0 mg/kg，保护指数分别为5.2和8.0。进一步发现这两种化合物对戊四氮、异烟肼、硫代氨基脲、3-巯基丙酸诱导的惊厥有强效活性，但对士的宁诱导的惊厥无效，表明这两种化合物可能通过增强γ-氨基丁酸神经传递发挥作用。
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