title: Synthesis and anticonvulsant activity of 7-phenyl-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones and their derivatives.
abstract: Herein, we described the syntheses and anticonvulsant activities of 7-(substituted-phenyl)-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones (1a-1o) and their derivatives. Most of the synthesized compounds exhibited potent anticonvulsant activities in the maximal electroshock test (MES). The most promising compound 1i showed significant anticonvulsant activity in MES test with ED(50) value of 19.7 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drugs. In addition, the potence of compound 1i against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide, 3-Mercaptopropionic acid, and Bicuculline in the chemical-induced seizure tests suggested that compound 1i displayed broad spectrum activity in several models, and it is likely to have several mechanisms of action including inhibiting voltage-gated ion channels and modulating GABAergic activity.
authors.affiliation: College of Pharmacy, Yanbian University, No. 977, Park road, Yanji, Jilin 133002, China.
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Quan
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Song
authors.forename: Cheng-Xi
authors.initials: CX
authors.lastname: Wei
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000009:adverse effects; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D001640:Bicuculline / Q000009:adverse effects; D004597:Electroshock; D007538:Isoniazid / Q000009:adverse effects; D051379:Mice; D010433:Pentylenetetrazole / Q000009:adverse effects; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012663:Semicarbazides / Q000009:adverse effects; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D011744:Pyrimidinones; D012663:Semicarbazides; D014230:Triazoles; C005151:thiosemicarbazide; D015097:3-Mercaptopropionic Acid; D007538:Isoniazid; D010433:Pentylenetetrazole; D001640:Bicuculline