Synthesis and biological activities of non-peptide angiotensin receptor antagonists with tetrazole replaced imidazole ring.
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.
Wahhab
A
A
Department of Medical Biochemistry, University of Calgary, Alberta, Canada.
Smith
J
J
Moore
G J
GJ
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
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