Renin-inhibiting di- and tripeptides, a process for their preparation, agents containing them, and their use

Claim 1

A compound of the formula I ##STR53## in which R 1 denotes a radical of the formula II R.sup.a --W-- (II) in which W represents --CO--, --O--CO--, --SO 2 -- ior --NH--CO--, and R a represents hydrogen, (C 1 -C 10 )-alkyl which is saturated or singly or doubly unsaturated and which is unsubstituted or substituted by up to 3 identical or different radicals selected from the group consisting of hydroxyl, (C 1 -C 7 )-alkoxy, (C 1 -C 7 )-alkanoyloxy, carboxyl, (C 1 -C 7 )-alkoxycarbonyl, Cl, Br, amino, (C 1 -C 7 )-alkylamino, di-(C 1 -C 7 )-alkylamino, (C 1 -C 5 )-alkoxycarbonylamino, (C 7 -C 15 )-aralkoxycarbonyl-amino and 9-fluorenylmethoxycarbonylamino, or represents (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl, (C 6 -C 14 )-aryl which is unsubstituted or substituted by one or two identical or different radicals selected from the group consisting of F, Cl, Br, I, hydroxyl, (C 1 -C 7 )-alkoxy, (C 1 -C 7 )-alkyl, (C 1 -C 7 )-alkoxycarbonyl, amino, anilino which is unsubstituted or substituted by up to 2 halogens, and trifluoromethyl, or represents (C 6 -C 14 )-aryl-(C 1 -C 6 )-alkyl in which the aryl moiety is unsubstituted or substituted by one or two identical or different radicals selected from the group consisting of F, Cl, Br, I, hydroxyl, (C 1 -C 7 )-alkoxy, (C 1 -C 7 )-alkyl, (C 1 -C 7 )-alkoxycarbonyl, amino, (C 1 -C 7 )-alkylamino, di-(C 1 -C 7 )-alkylamino, carboxyl, carboxymethoxy, amino(C 1 -C 7 )-alkyl, (C 1 -C 7 )-alkylamino-(C 1 -C 7 )-alkyl, di-(C 1 -C 7 )-alkylamino-(C 1 -C 7 )-alkyl, (C 1 -C 7 )-alkoxycarbonylmethoxy, carbamoyl, sulfamoyl, (C 1 -C 7 )-alkoxysulfonyl, sulfo- and guanidino-methyl, or represents the radical of a 5- or 6-membered monocyclic, or 9- or 10-membered bicyclic, heteroaromatic compound which has at least 1 carbon atom, 1-4 nitrogen atoms and/or 1 sulfur or oxygen atom, as ring members, and is unsubstituted or is mono-, di or trisubstituted independently by a member selected from the group of substitutents as defined for (C 6 -C 14 )-aryl above, R 4 denotes a radical of the formula IV --X--(CH.sub.2).sub.n '--R.sup.7 (IV) A denotes a radical, which is linked N-terminally with R 1 and C-terminally with B, of an amino acid selected from the group consisting of phenylalanine, histidine, tyrosine, tryptophan, methionine, leucine, isoleucine, asparagine, aspartic acid, β-2-thienylalanine, β-3-thienylalanine, β-2-furylalanine, β-3-furylalanine, lysine, ornithine, valine, alanine, 2,4-diaminobutyric acid, arginine, 4-chlorophenyl-aalanine, methionine sulfone, methionine sulfoxide, 2-pyridylalanine, 3-pyridylalanine, cyclohexylalanine, cyclohexylglycine, im-methylhistidine, 0-methyltyrosine, 0-benzyltyrosine, O-tert.-butyltyrosine, phenylglycine, 1-naphthylalanine, 2-naphthylalanine, 4-nitrophenylalanine, β-2-benzo(b)thienylalanine, β-3-benzo(b)thienylalanine, 2-fluorophenylalanine, 3-fluorophenylalanmine, 4-fluorophenylalanine, norleucine, cysteine, S-methylcysteine, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, homophenylalanine, DOPA, O-dimethyldopa, 2-amino-4-(2-thienyl)butyric acid, 2-amino-4-(3-thienyl)butyric acid, 3-(2-thienyl)serine, norvaline, (Z)-dehydrophenylalanine and (E)-dehydrophenylalanine, B denotes a radical of an amino acid as defined under A, R 2 denotes hydrogen, (C 1 -C 10 )-alkyl, (C 4 -C 7 )cycloalkyl, (C 4 -C 7 )-cycloalkyl-(C 1 -C 4 )-alkyl, (C 6 -C 14 )-aryl or (C 6 -C 14 )-aryl-(C 1 -C 4 )-alkyl, and R 3 denotes hydrogen, (C 1 -C 10 )-alkyl, (C 6 -C 14 )-aryl or (C 6 -C 14 )-aryl-(C 1 -C 4 )-alkyl, X can be chosen to be absent or denotes O or S, n' can be 0, 1, 2, 3 or 4, with the proviso that n' is not 0 if R 7 is OH or NH, R 7 denotes hydrogen, OH, NH 2 , or heteroaryl which can also be partially or completely hydrogenated or denotes a radical of the formula VI ##STR54## R 9 representing hydrogen, (C 1 -C 7 )-alkyl, or (C 1 -C 7 )-alkyl which is monosubstituted by hydroxyl, (C 1 -C 3 )-alkoxy, (C 1 -C 5 )-alkylthio, carboxyl, (C 1 -C 5 )-alkoxycarbonyl, F, Cl, Br, I, (C 1 -C 5 )-alkylamino, di-(C 1 -C 5 )-alkylamino, (C 1 -C 5 )-alkoxycarbonylamino or (C 7 -C 15 )-aralkoxycarbonylamino, R 10 denoting OH or NH 2 , Y being absent or denoting ##STR55## p, q, independently of each other denoting 0, 1, 2, 3 or 4, and in the case where Y is ##STR56## q not being equal to 0, and heteroaryl denoting the radical of a heteroaromatic compound defined under R 1 , and its physiologically tolerated salts.