title: Discovery of 4'-[(imidazol-1-yl)methyl]biphenyl-2-sulfonamides as dual endothelin/angiotensin II receptor antagonists.
abstract: A series of 4'-[(imidazol-1-yl)methyl]biphenylsulfonamides has potent antagonist activity against both angiotensin II AT(1) and endothelin ET(A) receptors. Such dual-acting antagonists could have utility in the treatment of hypertension, heart failure, and other cardiovascular diseases in a broad patient population. Certain compounds in the present series are orally active in a rat model of angiotensin II-mediated hypertension.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-5400, USA. jtellew@neurocrine.com
authors.forename: John E
authors.initials: JE
authors.lastname: Tellew
authors.forename: Rose Ann F
authors.initials: RA
authors.lastname: Baska
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Beyer
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Carlson
authors.forename: Lyndon A
authors.initials: LA
authors.lastname: Cornelius
authors.forename: Leena
authors.initials: L
authors.lastname: Fadnis
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Gu
authors.forename: Bridgette L
authors.initials: BL
authors.lastname: Kunst
authors.forename: Mark C
authors.initials: MC
authors.lastname: Kowala
authors.forename: Hossain
authors.initials: H
authors.lastname: Monshizadegan
authors.forename: Natesan
authors.initials: N
authors.lastname: Murugesan
authors.forename: Carol S
authors.initials: CS
authors.lastname: Ryan
authors.forename: Maria T
authors.initials: MT
authors.lastname: Valentine
authors.forename: Yifan
authors.initials: Y
authors.lastname: Yang
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018938:Caco-2 Cells; D015195:Drug Design; D065128:Endothelin Receptor Antagonists; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D007202:Indicators and Reagents; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D065128:Endothelin Receptor Antagonists; D007093:Imidazoles; D007202:Indicators and Reagents; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D013449:Sulfonamides