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Synthesis and anticonvulsant evaluation of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazoles

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Abstract

A series of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazole derivatives (3a-s) were synthesized as open-chain analogues of 7-hexyloxyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines (1c) using 4-hexyloxyaniline, acyl hydrazines, and dimethoxy-N,N-dimethylmethanamine as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). MES test showed that all open-chain compounds exhibited strong anticonvulsant activity and lower neurotoxicity, and that some possessed obviously stronger activity than compound 1c. Compound 3d, 3-propyl-4-(4-hexyloxyphenyl)-4H-1,2,4-triazole was found to be the most potent with an ED50 value of 5.7 mg/kg and protective index (PI = TD50/ED50) value of 11.5, which was much greater than that of the prototype drug phenytoin (PI = 6.9).

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 30460151) and Important Item Foundation of Ministry of Education P.R. China (no. 20070422029).

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Authors and Affiliations

  1. Key Laboratory of Organism Functional Factors of the Changbai Mountain, Yanbian University, Ministry of Education, Yanji, Jilin, 133002, China

    Xiang-Shu Cui & Zhe-Shan Quan

  2. College of Pharmacy, Yanbian University, 121, JuZi Street, Yanji City, Jilin Province, 133000, China

    Xiang-Shu Cui, Jing Chen & Zhe-Shan Quan

  3. Department of Chemistry, Wonkwang University, Iksan, 570-749, Korea

    Kyu-Yun Chai & Jin Seok Lee

Authors
  1. Xiang-Shu Cui
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  2. Jing Chen
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  3. Kyu-Yun Chai
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  4. Jin Seok Lee
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  5. Zhe-Shan Quan
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Correspondence to Zhe-Shan Quan.

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Cui, XS., Chen, J., Chai, KY. et al. Synthesis and anticonvulsant evaluation of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazoles. Med Chem Res 18, 49–58 (2009). https://doi.org/10.1007/s00044-008-9106-3

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  • DOI: https://doi.org/10.1007/s00044-008-9106-3

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