Transposition of the imidazole ring substituents of angiotensin mimetics related to Losartan.
A series of analogues related to Losartan in which the imidazole ring substituents were transposed have been prepared. Biological evaluation, both in vitro and in vivo, demonstrated that the orientation of the imidazole ring has a subtle yet significant effect upon the potency of these analogues. This information has provided an insight into the possible mode of receptor binding of Losartan and related compounds.
Smith
J R
JR
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Alberta, Canada.
Wahhab
A
A
Moore
D
D
Ganter
R C
RC
Moore
G J
GJ
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D019808:Losartan