Imidazole based non-peptide angiotensin II receptor antagonists. Investigation of the effect of the orientation of the imidazole ring on biological activity.
Non-peptide angiotensin II receptor antagonists related to losartan (DuP 753, CAS 114798-26-4) were prepared and evaluated for antagonist activity in the rat isolated uterus assay. The synthetic strategy concentrated on changes in the orientation of the imidazole ring relative to the substituents, which were maintained in a similar pattern to that found in losartan. The results indicate that biological activity of such antagonists shows little dependence on the orientation of the imidazole ring, but that the spacing of the substituents of primary importance.
Wahhab
A
A
Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
Smith
J R
JR
Ganter
R C
RC
Moore
D M
DM
Hondrelis
J
J
Matsoukas
J
J
Moore
G J
GJ
D000179:Acrylates / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000494:pharmacology; D013876:Thiophenes; D014590:Uterine Contraction / Q000187:drug effects
D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan; D019808:Losartan