title: Balanced AT1/AT2 receptor antagonists. 4. XR510 and related 5-(3-amidopropanoyl)imidazoles possessing equal affinity for the AT1 and AT2 receptors.
abstract: The identification of the AT1 and AT2 receptor subtypes has stimulated interest in developing balanced angiotensin II receptor antagonists. A series of 5-(3-amidopropanoyl)imidazoles has been prepared which possess balanced affinity for the AT1 and AT2 receptors. XR510 (1), 1-[[2'-[[(isopentoxycarbonyl)amino]sulfonyl]-3- fluoro(1,1'-biphenyl)-4-yl]methyl]-5-[3-(N-pyridin-3- ylbutanamido)propanoyl]-4-ethyl-2-propyl-1H-imidazole, potassium salt, exhibits subnanomolar affinity for both receptor sites. XR510 is very active in lowering blood pressure in renal hypertensive rats and furosemide-treated dogs following oral administration.
authors.affiliation: DuPont Merck Pharmaceutical Company, Experimental Station, Wilmington, Delaware 19880-0402, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Quan
authors.forename: A T
authors.initials: AT
authors.lastname: Chiu
authors.forename: C D
authors.initials: CD
authors.lastname: Ellis
authors.forename: P C
authors.initials: PC
authors.lastname: Wong
authors.forename: R R
authors.initials: RR
authors.lastname: Wexler
authors.forename: P B
authors.initials: PB
authors.lastname: Timmermans
mesh_terms: D000284:Administration, Oral; D000803:Angiotensin I / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; C095055:XR 510; D000803:Angiotensin I