Design,synthesis and anticonvulsant activity of N-(4-(4H-1,2,4-triazol-1-yl)phenyl)-2-phenoxyacetamide derivatives
LI Mengjiao
HU Lina
YI Shijia
JIN Bingbing
LEI Kang
WANG Shiben
Abstract：In this paper,a series of anticonvulsant derivatives containing triazole structure were designed and synthesized and the structures of the target compounds were confirmed by 1H NMR,13C NMR and HMRS methods.The results of maximal electroshock(MES),subcutaneous pentylenetetrazole(scPTZ)and rotating rod(ROT)assays showed that most of the compounds possessed anticonvulsant activity and low neurotoxicity.Among them,compound 5o showed a PI value of 11.5 and 8.2 in MES and scPTZ ex-periments,respectively,with a higher safety than the positive control carbamazepine of 6.1(MES test)and ethosuximide of 3.5(PTZ test).The test of inhibitory neurotransmitter GABA content in brain tissue further revealed that compound 5o exerted anticonvulsant activity may be associated with increased GABA content in rat brain.The molecular docking results indicated that the potential compound 5o was able to generate significant interaction force with the BZs binding active site amino acid residues of GABAA recep-tor.The results of this study suggest that compound 5o has the potential to serve as a lead compound con-taining a structural fragment of triazole.
Keywords：triazoleanticonvulsantsynthesisγ-gaba
Publication Date：2025-08-01
Online Publishing Date：2026-08-28(First online date of this platform, not the publication date of the document)
Pages：10( 615-624 )