title: The conformation and activity relationship of benzofuran type of angiotensin II receptor antagonists.
abstract: As a continuing effort to establish the structure and activity relationship in a benzofuran type of angiotensin II antagonist, we synthesized various regioisomers and performed a series of QSAR analyses. The conformational analyses of target isomers were carried out using molecular mechanics and fine-tuned using the information from the NMR NOE experiment. The conformations of compounds with a good binding activity are quite similar to that of DuP753, a prototype of AII antagonist, suggesting that these compounds also bind to the same site of AII receptor. We then studied the compounds with a varied length of the hydroxyl group bearing side chain to find out the optimum distance between the hydroxyl group and the imidazole ring. The CoMFA with these compounds gave acceptable statistical measures (cross-validated r2 and conventional r2 to be 0.881 and 0.974, respectively) and the map was well consistent with the previously proposed pharmacophore.
authors.affiliation: Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Taejon, South Korea. seyoo@pado.krict.re.kr
authors.forename: S E
authors.initials: SE
authors.lastname: Yoo
authors.forename: S K
authors.initials: SK
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: N J
authors.initials: NJ
authors.lastname: Kim
authors.forename: D W
authors.initials: DW
authors.lastname: Lee
mesh_terms: D000465:Algorithms; D057911:Angiotensin Receptor Antagonists; D001572:Benzofurans / Q000737:chemistry*; D001667:Binding, Competitive; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry
chemical_list: D057911:Angiotensin Receptor Antagonists; D001572:Benzofurans; D007093:Imidazoles; D013777:Tetrazoles; C045574:1H-tetrazole; C029899:imidazole; C105430:benzofuran