Parkinson's disease (PD) is a chronic neuro‐degenerative ailment characterized by impairment in various motor and nonmotor functions of the body. In the past few years, adenosine A₂A receptor (A₂AR) antagonists have attracted much attention due to significant relief in PD. Therefore, in the current study, we intend to disclose the development of novel 1,3,5‐triazines as A₂AR antagonist. The radioligand binding and selectivity of analogs were tested in HEK293 (human embryonic kidney) and the cells were transfected with pcDNA 3.1(+) containing full‐length human A₂AR cDNA and pcDNA 3.1(+) containing full‐length human A₁R cDNA, where they exhibit selective affinity for A₂AR. Molecular docking analysis was also conducted to rationalize the probable mode of action, binding affinity, and orientation of the most potent molecule (7c) at the active site of A₂AR. It has been shown that compound 7c form numerous nonbonded interactions in the active site of A₂AR by interacting with Ala59, Ala63, Ile80, Val84 Glu169, Phe168, Met270, and Ile274. The study revealed 1,3,5‐triazines as a novel class of A₂AR antagonists.

中文翻译：

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发现新型1,3,5-三嗪作为腺苷A2A受体拮抗剂可改善帕金森氏病

帕金森氏病（PD）是一种慢性神经退行性疾病，其特征是机体各种运动和非运动功能受损。在过去的几年中，由于PD的明显缓解，腺苷A ₂ A受体（A ₂ AR）拮抗剂引起了人们的广泛关注。因此，在当前的研究中，我们打算披露作为A ₂ AR拮抗剂的新型1,3,5-三嗪的开发。在HEK293（人类胚胎肾脏）中测试类似物的放射性配体结合和选择性，并用含有全长人A ₂ AR cDNA的pcDNA 3.1（+）和含有全长人A ₁ R的pcDNA 3.1（+）转染细胞cDNA，它们对A ₂表现出选择性亲和力AR。还进行了分子对接分析，以使可能的作用方式，结合亲和力和最有效的分子（7c）在A ₂ AR活性位点处的取向合理化。已经显示化合物7c通过与Ala59，Ala63，Ile80，Val84 Glu169，Phe168，Met270和Ile274相互作用而在A ₂ AR的活性位点形成许多非键合的相互作用。研究发现1,3,5-三嗪是一类新型的A ₂ AR拮抗剂。