CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
Departamento Quimica Orgánica, Facultade de Farmacia, Universidad Santiago de Compostela, Santiago de Compostela, Spain.
Chem Biol Drug Des. 2018 Jan;91(1):245-256. doi: 10.1111/cbdd.13075. Epub 2017 Sep 4.
Adenosine receptor (AR) subtypes are involved in several physiological and pharmacological processes. Ligands that are able to selectively modulate one receptor subtype can delay or slow down the progression of diverse diseases. In this context, our research group focused its investigation into the discovery and development of novel, potent and selective AR ligands based on coumarin scaffold. Therefore, a series of 3-phenylcarboxamidocoumarins were synthesized and their affinity for the human AR subtypes was screened by radioligand binding assays for A , A and A receptors and for A by adenylyl cyclase assay. Compound 26 was found to be the most remarkable, with a hA /hA and hA /hA selectivity of 42, for the A AR (K = 2.4 μm). Receptor-driven molecular modelling studies have provided valuable information on the binding/selectivity data of compound 26 and for the following optimization process. Moreover, compound 26 presents drug-like properties according to the general guidelines linked to the concept.
腺苷受体 (AR) 亚型参与多种生理和药理学过程。能够选择性调节一种受体亚型的配体可以延缓或减缓多种疾病的进展。在这方面，我们的研究小组专注于发现和开发基于香豆素骨架的新型、有效和选择性的 AR 配体。因此，合成了一系列 3-苯基羧酰胺香豆素，并通过放射性配体结合测定法筛选了它们对人 AR 亚型的亲和力，用于 A 、 A 和 A 受体，并用腺苷酸环化酶测定法用于 A 受体。发现化合物 26 是最显著的，对 A AR 的 hA /hA 和 hA /hA 选择性为 42，K 为 2.4 μm。受体驱动的分子建模研究为化合物 26 的结合/选择性数据和后续的优化过程提供了有价值的信息。此外，根据与概念相关的一般准则，化合物 26 具有类药性。
