beta(3)-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 conformat ional analysis carried out in water an a set of known beta (3)-adrenergic l igands. On the basis of their conformation at the global minimum, the molec ules under study can be grouped into two clusters: the 'extended' and the ' folded' cluster. Each cluster is identified by well-defined values of torsi on angles and distances between the pharmacophoric groups. It is worth noti ng that a ligand included in the cluster characterized by an extended confo rmation invariably shows a higher affinity for the human beta (3)-adrenorec eptor with respect to the corresponding rodent receptor. (C) 2001 Elsevier Science Ltd. All rights reserved.