Synthesis, Anticonvulsant Evaluation of 2,3,4,5-Tetrahydro-7-alkoxy-1H-2-benzazepin-1-ones

Authors: Wei, Cheng-Xi; Zhang, Wei; Quan, Zhe-Shan; Han, Rong-Bi; Jiang, Ri-Shan; Piao, Feng-Yu

Source: Letters in Drug Design & Discovery, Volume 6, Number 7, October 2009 , pp. 548-553(6)

Publisher: Bentham Science Publishers

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Abstract:

A series of novel 2,3,4,5-tetrahydro-7-alkoxy-1H-2-benzazepin-1-ones derivatives was synthesized and screened for its anticonvulsant activities by the maximal electroshock (MES) test and its neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The MES is the most commonly used method of screening antiepileptic drugs. 2,3,4,5-tetrahydro-7-heptyloxy-1H-2-benzazepin-1-one 4e, revealed as the best anticonvulsant activity, exhibited median effective dose (ED50) of 39.4 mg/kg, and median toxicity dose (TD50) of 392.9 mg/kg, resulting in a protective index (PI) of 10.0, which is a little higher than the PI of the marked antiepileptic drug carbamazepine (PI=6.4). Comound 4e also underwent further anticonvulsant tests evaluating its activity in some chemically induced seizure models, including pentylenetetrazole (PTZ), isoniazid, 3-mercaptopropionic acid (3-MP), and thiosemicarbazide.

Keywords: Anticonvulsant; Benzo[c]azepinone; Synthesis

Document Type: Research article

Publication date: 2009-10-01

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