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; B. Peng; W.-B. Zhang; W. Zhang; R.-B. Han

doi:10.1055/s-0031-1301295

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2012; 62(04): 202-207
DOI: 10.1055/s-0031-1301295

Original Article

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

¹Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China

,

B. Peng

¹Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China

,

W.-B. Zhang

¹Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China

,

W. Zhang

¹Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China

,

R.-B. Han

¹Department of Chemistry, College of Science, Yanbian University, Jilin Province, P.R. China

²Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Jilin Province, P. R. China

› Author Affiliations

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

Full Text

References

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