1. Synthesis and in vitro anti-epileptic activities of novel [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one derivatives.
- Author
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Ding, Jing, Cao, Feng-De, Geng, Yan-Ru, Tian, Yuan, Li, Peng, Li, Xiu-Fen, and Huang, Long-Jiang
- Subjects
DRUG therapy for convulsions ,ANIMAL experimentation ,ANTICONVULSANTS ,BACTERIA ,CELL culture ,CELL receptors ,ANALYTICAL chemistry ,EPILEPSY ,GABA ,MICE ,MOLECULAR structure ,NEUROBIOLOGY ,NUCLEAR magnetic resonance spectroscopy ,RESEARCH funding ,SPASMS ,IN vitro studies ,PHARMACODYNAMICS - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2019
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