Department of Pharmacy, University of Pisa, Pisa, Italy.
Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):286-294. doi: 10.1080/14756366.2020.1862103.
Small-molecules acting as positive allosteric modulators (PAMs) of the A adenosine receptor (A AR) could potentially represent a novel therapeutic strategy for pathological conditions characterised by altered bone homeostasis, including osteoporosis. We investigated a library of compounds (-) exhibiting different degrees of chemical similarity with three indole derivatives (-), which have been recently identified by us as PAMs of the A AR able to promote mesenchymal stem cell differentiation and bone formation. Evaluation of mineralisation activity of - in the presence and in the absence of the agonist BAY60-6583 allowed the identification of lead compounds with therapeutic potential as anti-osteoporosis agents. Further biological characterisation of one of the most performing compounds, the benzofurane derivative , confirmed that such a molecule behaves as PAM of the A AR.
作为 A 腺苷受体 (A AR) 的正变构调节剂 (PAM) 的小分子，可能代表了一种治疗病理性骨稳态改变的新策略，包括骨质疏松症。我们研究了一组化合物 (-)，它们与我们最近鉴定的三种吲哚衍生物 (-) 在化学相似性上存在不同程度的差异，这些吲哚衍生物被鉴定为 A AR 的 PAM，能够促进间充质干细胞分化和骨形成。在激动剂 BAY60-6583 的存在和不存在的情况下，评估 - 对矿化活性的影响，从而确定具有治疗潜力的先导化合物，作为抗骨质疏松药物。对表现最出色的化合物之一，苯并呋喃衍生物 的进一步生物学特性的研究证实，这种分子是 A AR 的 PAM。
