Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
J Pharm Pharmacol. 2013 May;65(5):697-703. doi: 10.1111/jphp.12028. Epub 2013 Jan 25.
With the aim of finding new adenosine receptor (AR) ligands based on the chalcone scaffold, we report the synthesis of a new series of coumarin-chalcone hybrids and the pharmacological characterization of their actions at four subtypes of AR.
The synthesized compounds 5-10 were characterized in radioligand binding (A1 , A2A and A3 ) and adenylyl cyclase activity assays (A2B ) to determine the affinity of the compounds for the four human AR (hAR) subtypes.
Coumarin-chalcone hybrids were found to be ligands with a novel structure, not reported thus far, that showed varying affinity and selectivity for AR subtypes.
The coumarin-chalcone hybrids in which ring B of the chalcone scaffold was a thiophene (compounds 5 and 9) were found to be the most potent compounds of the series. Compound 9, in which ring A of the chalcone moiety was the phenyl ring of the coumarin, showed similar activity against hA1 , hA2A and hA3 ARs, while compound 5, in which ring A of the chalcone was substituted by the benzopyrone ring of the coumarin moiety, showed similar activity only at the hA3 AR and, therefore, was deemed to be selective (Ki (dissociation constant) = 5160 nm).
为了寻找基于查尔酮骨架的新型腺苷受体（AR）配体，我们报告了一系列新的香豆素-查尔酮杂合体的合成及其在四种 AR 亚型中的作用的药理学特征。
合成的化合物 5-10 通过放射性配体结合（A1、A2A 和 A3）和腺苷酸环化酶活性测定（A2B）进行表征，以确定化合物对四种人 AR（hAR）亚型的亲和力。
香豆素-查尔酮杂合体被发现是具有新型结构的配体，迄今为止尚未报道，它们对 AR 亚型表现出不同的亲和力和选择性。
在查尔酮骨架的环 B 为噻吩的香豆素-查尔酮杂合体（化合物 5 和 9）中发现是该系列中最有效的化合物。其中，查尔酮部分的环 A 为香豆素的苯基环的化合物 9 对 hA1、hA2A 和 hA3 AR 具有相似的活性，而查尔酮部分的环 A 被香豆素的苯并吡喃环取代的化合物 5 仅在 hA3 AR 中表现出相似的活性，因此被认为是选择性的（Ki（解离常数）= 5160nm）。
