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

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.

Keywords:

• 1,2,4-triazolo[1,5-a]pyrimidine-7(4H)-one
• synthesis
• anti-epileptic
• molecular docking

Disclosure statement

No potential conflict of interests was reported by the authors.

Additional information

Funding

This work was financially supported by the Opening Foundation of State Key Laboratory of Bioactive Substance and Function of Natural Medicine (No. GTZK201805) and the Shandong Province Higher Educational Science and Technology Program (No. J16LC13).