title: In vitro pharmacological characterization of a new selective angiotensin AT1 receptor antagonist, UR-7280.
abstract: UR-7280 (3-tert-butyl-1-propyl-5-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-y l]methyl]-1H-pyrazole-4-carboxylic acid) is a new and potent angiotensin AT1-selective receptor antagonist. Binding studies in rat liver membranes showed that UR-7280 is an apparently competitive antagonist. However, in rabbit aorta this compound antagonized the angiotensin II-induced contractile response in an insurmountable way, causing a significant reduction of the maximal response. Additional binding studies evidenced that UR-7280 has a slowly reversible binding profile, consistent with its functional properties in rabbit aorta. The results obtained with a series of structural analogues of UR-7280 demonstrated a relationship between the size of the pyrazole 3-substituent and the surmountable or insurmountable mode of antagonism, indicating that this position may play a key role in the interaction between the antagonist and the angiotensin AT1 receptor.
authors.affiliation: Pharmacology Laboratory, Research Center, J. Uriach & Cia S.A., Barcelona, Spain.
authors.forename: A F
authors.initials: AF
authors.lastname: De Arriba
authors.forename: L A
authors.initials: LA
authors.lastname: Gómez-Casajús
authors.forename: F
authors.initials: F
authors.lastname: Cavalcanti
authors.forename: C
authors.initials: C
authors.lastname: Almansa
authors.forename: J
authors.initials: J
authors.lastname: García-Rafanell
authors.forename: J
authors.initials: J
authors.lastname: Forn
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D011720:Pyrazoles; D013777:Tetrazoles; C105773:UR 7280; D000804:Angiotensin II