Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3-a]azepines as Anticonvulsant Agents

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.

Cite this article as:

Wu Hui-Fan, Han Rong-Bi, Jin Chun-Zi and Piao Feng-Yu, Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3-a]azepines as Anticonvulsant Agents, CNS & Neurological Disorders - Drug Targets 2016; 15 (10) . https://dx.doi.org/10.2174/1871527315666160321111211