Figure 1.
Workflow of the computational pipeline. Selection of naphthalene bioisosteres was guided by a previous study focused on A3AR agonists. Between the two proposed alternatives, the triazole analogue resulted as being the most promising according to membrane MD simulations analysis of the ligand–protein complexes as compared with the reference compound. Consequently, a small library of 57 triazole analogues was designed and docked inside the hP2Y14R. Poses were selected by visual inspection. The synthesis and experimental validation of the compounds were prioritized according to the overlap between compounds functional groups and protein interaction sites.