title: Synthesis and biological activities of non-peptide angiotensin receptor antagonists with tetrazole replaced imidazole ring.
abstract: Angiotensin receptor antagonists related to losartan were synthesized in which the imidazole ring was replaced by tetrazole. 1-[4-(2'-Carboxyphenyl)benzyl]-5-butyl tetrazole and 5-[4-(2'-carboxyphenyl)benzyl]-1-butyl tetrazole had antagonist activities versus angiotensin II in the rat isolated uterus assay of 70% and 10%, respectively, of that of the equivalent imidazole compound 1-[4-(2'-carboxyphenyl)benzyl]-2-butyl imidazole. These data suggest that the antagonist activity of compounds in this class is not dependent on the direction of the heterocyclic ring dipole, and that there is a preference for substitution of the acid group-bearing side-chain at the N atom rather than the C atom of tetrazole.
authors.affiliation: Department of Medical Biochemistry, University of Calgary, Alberta, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Wahhab
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: G J
authors.initials: GJ
authors.lastname: Moore
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects
chemical_list: C083508:1-butyl-5-(4-(2'-carboxyphenyl)benzyl)tetrazole; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D013777:Tetrazoles; C083509:5-butyl-1-(4-(2'-carboxyphenyl)benzyl)tetrazole