title: Derivation of a 3D pharmacophore model for the angiotensin-II site one receptor.
abstract: A systematic search has been used to derive a hypothesis for the receptor-bound conformation of A-II antagonists at the AT1 receptor. The validity of the pharmacophore hypothesis has been tested using CoMFA, which included 50 diverse A-II antagonists, spanning four orders of magnitude in activity. The resulting cross-validated R2 of 0.64 (conventional R2 of 0.76) is indicative of a good predictive model of activity, and has been used to estimate potency for a variety of non-peptidyl antagonists. The structural model for the non-peptide has been compared with respect to the natural substrate, A-II, by generating peptide to non-peptide overlays.
authors.affiliation: Molecular Systems Department, Merck Research Laboratories, Rahway, NJ 07065.
authors.forename: K
authors.initials: K
authors.lastname: Prendergast
authors.forename: K
authors.initials: K
authors.lastname: Adams
authors.forename: W J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: R B
authors.initials: RB
authors.lastname: Nachbar
authors.forename: A A
authors.initials: AA
authors.lastname: Patchett
authors.forename: D J
authors.initials: DJ
authors.lastname: Underwood
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D001665:Binding Sites; D017076:Computer-Aided Design; D015195:Drug Design; D004563:Electrochemistry; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011945:Receptors, Angiotensin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809