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  • Title: Synthesis and anticonvulsant activity of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines.
    Author: Zhang L, Guan LP, Sun XY, Wei CX, Chai KY, Quan ZS.
    Journal: Chem Biol Drug Des; 2009 Mar; 73(3):313-9. PubMed ID: 19207467.
    Abstract:
    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.
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