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Synthesis and evaluation of the anticonvulsant activities of 2,3-dihydrophthalazine-1,4-dione derivatives

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Abstract

A series of 2,3-dihydrophthalazine-1,4-dione derivatives with triazole (6a–y) and other heterocyclic substituents (8a–b, 9a–b, 10a–b, 12a–b, and 14a–b) was synthesized and their structures characterized by using IR, 1H-NMR, 13C-NMR, and MS. Their anticonvulsant activities were evaluated using the maximal electroshock test, and their neurotoxicity was evaluated using the rotarod neurotoxicity test (Tox). The results showed that 5-(3-(trifluoromethyl)benzyl)-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one (6e) had the most potent anticonvulsant activity with an ED50 value of 6.8 mg/kg and protective index (PI = TD50/ED50) value of 11.5 (i.p.); its anticonvulsant activity was found to be stronger than that of the lead compound and the standard drug carbamazepine. In particular, compound 6e protected against the seizures induced by pentylenetetrazole and bicuculline.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81360468 and 21662036)

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  1. Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China

    Xiang-Jun Liu, Hong-Jian Zhang & Zhe-Shan Quan

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  1. Xiang-Jun Liu
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  2. Hong-Jian Zhang
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  3. Zhe-Shan Quan
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Correspondence to Zhe-Shan Quan.

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Liu, XJ., Zhang, HJ. & Quan, ZS. Synthesis and evaluation of the anticonvulsant activities of 2,3-dihydrophthalazine-1,4-dione derivatives. Med Chem Res 26, 1935–1946 (2017). https://doi.org/10.1007/s00044-017-1896-8

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