Synthesis and in vitro anti-epileptic activities of novel [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one derivatives

被引：21

作者：

Ding, Jing ^{[1
]}

Cao, Feng-De ^{[1
]}

Geng, Yan-Ru ^{[1
]}

Tian, Yuan ^{[1
]}

Li, Peng ^{[1
]}

Li, Xiu-Fen ^{[1
]}

Huang, Long-Jiang ^{[1
,2
]}

机构：

[1] Qingdao Univ Sci & Technol, Coll Chem Engn, Qingdao 266061, Shandong, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China

来源：

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH | 2019年 / 21卷 / 12期

关键词：

1; 2; 4-triazolo[1; 5-a]pyrimidine-7(4H)-one; synthesis; anti-epileptic; molecular docking; ANTICONVULSANT ACTIVITY EVALUATION; DRUGS; NEURONS;

D O I：

10.1080/10286020.2018.1529030

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

In this investigation, eight novel 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one and eight novel 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine amine derivatives were synthesized based on the novel marine natural product Essramycin. Their anti-epileptic activities were evaluated by 4-aminopyridine (4-AP)-induced hyper excitability model in primary cultured neocortical neurons. Five compounds with [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one skeleton showed remarkable anti-epileptic activities. The preliminary structure-activity relationship (SAR) showed that the pyrimidine-7(4H)-one motif is the necessary "active core" of anti-epileptic activity. To understand the action mechanism of anti-epileptic activity of [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one compounds, docking studies using the model of GABA(A) as docking scaffolds were performed and the docking results were in concordance with the experiment observations.

引用

页码：1190 / 1204

页数：15

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