Novel positive allosteric modulators of A adenosine receptor acting as bone mineralisation promoters.

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.