Angiotensin-II analogues with antagonizing effects, containing an alpha -hydroxycarboxylic acid residue in position 8, and a process for the preparation thereof

New angiotensin-II analogues of the general formula (I), X-Arg-Val-Tyr-Ile-His-Pro-Y-OA (I) wherein X stands for the acyl group of an N-methylamino acid, or the acyl group of an aliphatic alpha -aminooxy- or alpha -hydroxycarboxylic acid, Y is the residue of an aliphatic alpha -hydroxycarboxylic aci...

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Hauptverfasser: NYEKI, OLGA, KARPATI, EGON, SZPORNY, LASZLO, KISFALUDY, LAJOS
Format: Patent
Sprache:eng
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Zusammenfassung:New angiotensin-II analogues of the general formula (I), X-Arg-Val-Tyr-Ile-His-Pro-Y-OA (I) wherein X stands for the acyl group of an N-methylamino acid, or the acyl group of an aliphatic alpha -aminooxy- or alpha -hydroxycarboxylic acid, Y is the residue of an aliphatic alpha -hydroxycarboxylic acid, and A is hydrogen or a C1-5 alkyl group, are prepared by removing the protecting groups of a protected octapeptide derivative of the general formula (II) or (III), B-X-Arg(C)-Val-Tyr(D)-Ile-His(E)-Pro-Y-OF (II) B-X-Arg(C)-Val-Tyr(D)-Ile-His(E)-Pro-Y-OA (III) wherein B is a group removable by acidolysis or catalytic hydrogenation, C is a group for the temporary protection of the guanidino group on the Arg moiety, D is a group for the temporary protection of the aromatic hydroxy group on the Tyr moiety, E is a group for the temporary protection of the imidazole group on the His moiety, and F is a group for the protection of the terminal carboxy group, resistant to the effect of mild acids but removable by catalytic hydrogenolysis or upon treatment with a stronger acid. The new compounds of the invention can be applied to diagnose and differentiate hypertensions of various origin, and in the therapy to suppress hypertensions of renal origin, in the treatment of hypertensive crises, secondary cardiac insufficiency, etc.