title: A comparative molecular field analysis and molecular modelling studies on pyridylimidazole type of angiotensin II antagonists.
abstract: A large number of compounds known as "AII (Angiotensin II) antagonists" have been developed for the treatment of various heart diseases such as hypertension, congestive heart failure, and chronic renal failure. Most of the currently known AII receptor antagonists share a similar chemical structure, consisting of nitrogen atoms, a lipophilic alkyl side chain and an acidic group. As a new series, we have designed and synthesized various pyridylimidazole derivatives. In this report we would like to discuss the structure-activity relationship of these series of compounds using the comparative molecular field analysis (CoMFA) methods. We could come up with a good CoMFA model (cross-validated and conventional r2 values equal to 0.702 and 0.991, respectively) and the validity of the model was confirmed by synthesizing and measuring their biological activity of additional 6 compounds suggested by the model. This result provides additional information on the structural requirement for structurally diverse group of AII receptor antagonists.
authors.affiliation: Bio-Organic Science Division 5, Korea Research Institute of Chemical Technology, Daejon, 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: K Y
authors.initials: KY
authors.lastname: Yi
authors.forename: D W
authors.initials: DW
authors.lastname: Lee
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II