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Arzneimittelforschung 2012; 62(04): 202-207
DOI: 10.1055/s-0031-1301295
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis and Biological Evaluation of 9-alkoxy-6,7-dihydro-5H-benzo[c] [1,2,4]triazolo[4,3-a]azepines as Potential Anticonvulsant Agents

F.-Y. Piao
1   Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China
,
B. Peng
1   Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China
,
W.-B. Zhang
1   Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China
,
W. Zhang
1   Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China
,
R.-B. Han
1   Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China
2   Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Jilin Province, P. R. China
› Author Affiliations
Further Information

Publication History

received 19 October 2011

accepted 03 January 2012

Publication Date:
27 January 2012 (online)

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Abstract

A novel series of 9-alkoxy-6,7-dihydro-5H-benzo[c][1,2,4]triazolo[4,3-a]azepine derivatives was synthesized and screened for anticonvulsant activity by the maximal electroshock (MES) test and the subcutaneous pentylenetetrazol (scPTZ) test. Neurotoxic effects were also determined by the rotarod neurotoxicity test. The results revealed that all of the compounds exhibited anticonvulsant activity, Compound 5d was found to possess the most potential anticonvulsant activity in the anti-MES potency test; it had a median effective dose (ED50) of 12.3 mg/kg, a median toxicity dose (TD50) of 73.5 mg/kg, and a protective index (PI) of 6.0, which is slightly lower than the PI of the prototype drug carbamazepine (ED50=8.8, PI=8.1). In the scPTZ test, compound 5c was the most active, with an ED50 value of 19.8 mg/kg, a TD50 value of 80.8 mg/kg and a PI value of 4.1, which are much greater than the ED50 and the PI of the prototype drug carbamazepine (ED50>100, PI<0.72), Possible structure-activity relationships are also discussed.

Key words

benzotriazoloazepine - synthesis - anticonvulsant activity
 

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