Synthesis of 5-Alkoxythieno2,3-e1,2,4triazolo4,3-cpyrimidine Derivatives and Evaluation of Their Anticonvulsant ActivitiesReportar como inadecuado




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Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, China





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Academic Editor: Derek J. McPhee

Abstract This work concerns the design and synthesis of novel, substituted 5-alkoxythieno2,3-e1,2,4triazolo4,3-cpyrimidine derivatives 5a–p prepared from 3-amino-2-thiophenecarboxylic acid methyl ester. The final compounds were screened for their in vivo anticonvulsant activity using maximal electroshock MES and subcutaneous pentylenetetrazole scPTZ tests. Neurotoxicity NT was tested using a rotarod test. The structure-anticonvulsant activity relationship analysis revealed that the most effective structural motif involves a substituted phenol, especially when substituted with a single chlorine, fluorine or trifluoromethyl group at the meta-position, or two chlorine atoms. These molecules possessed high activity according to the MES and scPTZ models. Quantitative assessment of the compounds after intraperitoneal administration in mice showed that the most active compound was 5-3-trifluoromethylphenoxythieno2,3-e 1,2,4triazolo4,3-cpyrimidine 5o with ED50 values of 11.5 mg-kg MES and 58.9 mg-kg scPTZ. Furthermore, compound 5o was more effective in the MES and scPTZ tests than the well-known anticonvulsant drugs carbamazepine and ethosuximide. View Full-Text

Keywords: synthesis; triazole; maximal electroshock; neurotoxicity; pentylenetetrazole synthesis; triazole; maximal electroshock; neurotoxicity; pentylenetetrazole





Autor: Shi-Ben Wang, Guang-Chun Piao, Hong-Jian Zhang and Zhe-Shan Quan *

Fuente: http://mdpi.com/



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