Studies on relationships between chemical structure and beta-blocking potency of bopindolol and its two metabolites

The structure-activity relationships of bopindolol and its two metabolites (18-502 and 20-785) and their beta-blocking potencies in the human beta2-adrenoceptor (AR) were assessed using molecular modeling on an INDIGO2 workstation (SGI Co., Ltd.) and DISCOVER/INSIGHT II (Biosym Co., Ltd.). Through modeling, possible binding sites for these agents were hypothesized to involve the 3rd, 4th, 5th and 6th helices of the beta2-AR, and these shared a common interaction site at Asp113 in helix 3. The different chemical structure of these three agents, however, showed binding to different binding sites (amino acids). This study therefore suggests that different beta-blocking potencies of these agents may be due to different chemical structure.