Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, I-44121 Ferrara, Italy.
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Piazzale Europa 1, I-34127 Trieste, Italy.
Mini Rev Med Chem. 2018;18(14):1168-1174. doi: 10.2174/1389557518666180423113051.
In the past decades, many efforts were undertaken to develop ligands for the adenosine receptors, with the purpose to individuate agonists and antagonists affinity and selectivity for each subtypes, namely A1, A2A, A2B, and A3. These intense studies allowed a deeper knowledge of the nature and, moreover, of the pathophysiological roles of all the adenosine receptor subtypes. In particular, the involvement of the A2A adenosine receptor subtype in some physiological mechanisms in the brain, that could be related to important diseases such as the Parkinson's disease, encouraged the research in this field. Particular attention was given to the antagonists endowed with high affinity and selectivity since they could have a real employment in the treatment of Parkinson's disease, and some compounds, such as istradefylline, preladenant and tozadenant, are already studied in clinical trials. Actually, the role of A2A antagonists in Parkinson's disease is becoming contradictory due to contrasting results in the last studies, but, at the same time, new possible employments are emerging for this class of antagonists in cancer pathologies as much interesting to legitimate further efforts in the research of A2A ligands.
在过去的几十年中，人们做出了许多努力来开发腺苷受体的配体，目的是确定每种亚型（即 A1、A2A、A2B 和 A3）的激动剂和拮抗剂的亲和力和选择性。这些深入的研究使我们更深入地了解了所有腺苷受体亚型的性质，而且还了解了它们的生理病理作用。特别是，A2A 腺苷受体亚型在大脑中的一些生理机制中的参与，可能与帕金森病等重要疾病有关，这促使人们在该领域进行了研究。人们特别关注具有高亲和力和选择性的拮抗剂，因为它们可能在帕金森病的治疗中有实际应用，并且一些化合物，如伊曲茶碱、普莱登坦和托扎丹坦，已经在临床试验中进行了研究。实际上，由于最近的研究结果相互矛盾，A2A 拮抗剂在帕金森病中的作用变得相互矛盾，但与此同时，这种拮抗剂类别的新的可能用途也在癌症病理中出现，这使得进一步研究 A2A 配体成为了非常有趣的课题。
