β3-Adrenergic receptor ligands: insight into structure–activity relationships using Monte-Carlo conformational analysis in water

This paper deals with the application of a Monte-Carlo (MC)-based conformational analysis carried out in water on a set of known β3-adrenergic ligands. On the basis of their conformation at the global minimum, the molecules under study can be grouped into two clusters: the ‘extended’ and the ‘folded’ cluster. Each cluster is identified by well-defined values of torsion angles and distances between the pharmacophoric groups. It is worth noting that a ligand included in the cluster characterized by an extended conformation invariably shows a higher affinity for the human β3-adrenoreceptor with respect to the corresponding rodent receptor.