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Molecules 2015, 20(4), 6827-6843; doi:10.3390/molecules20046827

Synthesis of 5-Alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine Derivatives and Evaluation of Their Anticonvulsant Activities

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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Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 12 March 2015 / Revised: 2 April 2015 / Accepted: 8 April 2015 / Published: 15 April 2015
(This article belongs to the Section Medicinal Chemistry)
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Abstract

This work concerns the design and synthesis of novel, substituted 5-alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives 5ap 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-(trifluoromethyl)phenoxy]thieno[2,3-e] [1,2,4]triazolo[4,3-c]pyrimidine (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
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, S.-B.; Piao, G.-C.; Zhang, H.-J.; Quan, Z.-S. Synthesis of 5-Alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine Derivatives and Evaluation of Their Anticonvulsant Activities. Molecules 2015, 20, 6827-6843.

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