ANGIOTENSIN-II ANALOGS .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)4]AII, 0.1%; [AsnTyr(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. © 1979, American Chemical Society. All rights reserved.