Angiotensin II analogues. 13. Role of the hydroxyl group of position 4 tyrosine in pressor activity.
In order to determine the features of the phenolic ring in position 4 of [Asn1,Ile5]angiotensin II that contribute to pressor activity, analogues with selected aromatic substituents were synthesized by the solid-phase method. They showed pressor activities in the rat: [Asn1,Phe(4-NH2)4]AII, 24%; [Asn1,Phe(4-NO2)4AII, 0.1%; [Asn1,Tyr(3,5-Me2)4]AII, 2.2%; [Asn1,D-Tyr(3,5-Me2)4]AII, 1.4%. These results indicate that the activity contributed by the aromatic character of the phenyl ring in the side chain of position 4 is enhanced by a group in the para position that may function as a proton donor in hydrogen-bond formation. Bulky substituents ortho to this hydrogen-bonding group decrease activity by steric interference with hydrogen-bond formation. Bulky groups than cannot act as hydrogen donors in the para position of the aromatic ring drastically decrease the activating effect of the aromatic ring on pressor activity.
D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000809:Angiotensins / Q000031:analogs & derivatives*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D008297:Male; D051381:Rats; D013329:Structure-Activity Relationship; D014443:Tyrosine
D000809:Angiotensins; D014443:Tyrosine; D000803:Angiotensin I