Studies on position 1 of angiotensin II: effects on affinity and duration of action from alkyl amide substitution.
The synthesis and the biological activities of [asparagine]angiotensin II analogues with alkyl-substituted amide groups are reported. This study was performed in order to elucidate further the importance and the influence of the side chain in position 1 of angiotensin II. The two synthesized analogues [1-(N4,N4-dipropyl)asparagine]- and [1-(N4,N4-diisopropyl)asparagine]angiotensin II were compared to [1-asparagine]angiotensin II (hypertensin, Ciba) and to [1-(N4,N4-dimethyl)asparagine]angiotensin II in vitro and in vivo. All compounds had full intrinsic activity, but their potency decreased with increasing alkyl size of the substituted carboxamide group. Despite their reduced potency, the alkylated analogues showed enhanced duration of action on rabbit aorta strips. The relative potencies of the series hypertensin, dimethyl, dipropyl, and diisopropyl analogues on rabbit aorta strips were 100, 46, 16, and 9%, respectively. In the rat blood pressure assay they were 100, 30, 9, and 7%, respectively.
D000478:Alkylation; D000577:Amides; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
D000577:Amides; D000804:Angiotensin II