Title:Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3-a]azepines as Anticonvulsant Agents
Volume: 15
Issue: 10
Author(s): Hui-Fan Wu, Rong-Bi Han, Chun-Zi Jin and Feng-Yu Piao
Affiliation:
Keywords:
Anticonvulsant activity, Benzotriazoloazepine, Synthesis, Triazole, Toxicity.
Abstract: A series of new 8-alkylamino-5, 6-dihydro-4H-benzo[f][1,2,4]triazolo [4,3-a]azepine
derivatives were synthesized and screened for their anticonvulsant activities by the maximal
electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was
evaluated by the rotarod neurotoxicity test. The results of these tests showed that 8-heptylamino-5,6-
dihydro-4H-benzo[f][1,2,4] triazolo[4,3-a]azepine (7g) was the most promising compound, with median
effective dose (ED50) of 19.0 mg/kg, and protective index (PI) value of 14.8 in the MES test, which is
much higher than the PI value of the prototype antiepileptic drug carbamazepine (PI = 8.1), phenytoin
(PI = 6.9), phenobarbital (PI = 3.2), and sodium valproate (PI = 1.6). The possible structure–activity
relationship was discussed.
