Angiotensin-ii analogues with antagonizing effects,...

Details Angiotensin-ii analogues with antagonizing effects,... Angiotensin-ii analogues with antagonizing effects,...

C - Chemistry, Metallurgy

07

K

530/7.06

C07K 7/14 (2006.01)

Patent

CA 1149377

ABSTRACT OF THE DISCLOSURE 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.-hydroxy- carboxylic acid, Y is tha 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 differentiabe hypertensions of various origin, and in the therapy to suppress hypertensions of renal origln, in the treatment of hypertensive crises, secondary cardiac insufficiency, etc.

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