Amino acid derivatives useful for treating high blood pressure

A composition for treating or preventing high blood pressure or cardiac insufficiency comprising an effective amount of a compound of the formula ##STR16## wherein R.sup.1 is hydrogen or methyl;

• R.sup.2 is ethyl, propyl, isopropyl, imidazol-2-yl, imidazol-4-yl, pyrazol-3-yl, thiazol-4-yl, thien-2-yl, ethoxycarbonyl, t-butylcarbonylmethyl, benzyloxycarbonylmethyl or t-butoxy;
• R.sup.3 is isobutyl, cyclohexylmethyl or benzyl;
• R.sup.4 is a group of the formula --N(R.sup.5)(R.sup.6);
• and A is one of the groups ##STR17## wherein R.sup.5 is alkyl, R.sup.6 is an acyl radical or an amino acid or a dipeptide, which amino acid or dipeptide is unsubstituted or substituted N-terminally by an acyl of a carboxylic acid;
• R.sup.7 is phenyl, phenyl which is mono- or multiply-substituted with alkyl, alkoxy, alkoxyalkoxy, alkanoyl, alkanoyloxy, hydroxy, halogen or trifluoromethyl, or benzyl or naphthyl;
• and R.sup.8 is hydrogen, alkoxycarbonylalkyl, alkylcarbonylalkyl, cycloalkylcarbonylalkyl, heterocycloalkylcarbonylalkyl, arylcarbonylalkyl, aminocarbonylalkyl, substituted aminocarbonylalkyl, aminoalkylcarbonylalkyl, substituted aminoalkylcarbonylalkyl, aminoalkylsulfonylalkyl, substituted aminoalkylsulfonylalkyl, alkoxycarbonylhydroxyalkyl, alkylcarbonylhydroxyalkyl, cycloalkylcarbonylhydroxyalkyl, heterocycloalkylcarbonyl-hydroxyalkyl, arylcarbonyl-hydroxyalkyl, aminocarbonyl-hydroxyalkyl, substituted aminocarbonylhydroxyalkyl, dialkoxyphosphoroxyalkyl, diphenyl-oxyphosphoroxyalkyl, arylalkyl, alkoxycarbonylamino, arylalkoxycarbonylamino, alkythioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, arylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl, arylalkylthioalkyl, arylalkylsulfinylalkyl or arylalkylsulfonylalkyl, where the substituted amino portion of the above R.sup.8 moieties is an amino group which is mono- or di-substituted by alkyl, arylalkyl, alkanoyl, alkoxycarbonyl or arylalkoxycarbonyl, or di-substituted by C.sub.3 -C.sub.6 -alkylene or C.sub.3 -C.sub.6 -alkylene which is interrupted by an oxygen, sulfur or nitrogen atom, the nitrogen atom being an unsubstituted or substituted with alkyl, phenylalkyl, alkanoyl or alkanoyloxy, with the proviso that R.sup.8 is not alkoxycarbonylamino or arylalkoxycarbonylamino when R.sup.7 is phenyl, benzyl or .alpha.-naphthyl;
• Y is a bivalent acyl radical or phenylglycine, cyclohexylglycine, phenylalanine, cyclohexylalanine, 4-fluorophenylalanine, 4-chlorophenylalanine, tyrosine, O-methyltyrosine, .alpha.-naphthylalanine or homophenylalanine, each of which is N- or .alpha.-methylated and is linked with Z at the T-terminal;
• and Z is hydrogen or an acyl of a carboxylic acid,
• in the form of optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates or a pharmaceutically usable salt of such compound.

A method for treating or preventing high blood pressure or cardiac insufficiency in a patient in need of such treatment comprising administering an effective amount of a compound of the formula ##STR18## wherein R.sup.1 is hydrogen or methyl;

• R.sup.2 is ethyl, propyl, isopropyl, imidazol-2-yl, imidazol-4-yl, pyrazol-3-yl, thiazol-4-yl, thien-2-yl, ethoxycarbonyl, t-butylcarbonylmethyl, benzyloxycarbonylmethyl or t-butoxy;
• R.sup.3 is isobutyl, cyclohexylmethyl or benzyl;
• R.sup.4 is a group of the formula --N(R.sup.5)(R.sup.6);
• and A is one of the groups ##STR19## wherein R.sup.5 is alkyl;
• R.sup.6 is an acyl radical of an amino acid or a dipeptide, which amino acid or dipeptide may be unsubstituted or substituted N-terminally by an acyl of a carboxylic acid;
• R.sup.7 is phenyl, phenyl which is mono- or multiply-substituted with alkyl, alkoxy, alkoxyalkoxy, alkanoyl, alkanoyloxy, hydroxy, halogen or trifluoromethyl, or benzyl or naphthyl;
• and R.sup.8 is hydrogen, alkoxycarbonylalkyl, alkylcarbonylalkyl, cycloalkylcarbonylalkyl, heterocycloalkylcarbonylalkyl, arylcarbonylalkyl, aminocarbonylalkyl, substituted aminocarbonylalkyl, aminoalkylcarbonylalkyl, substituted aminoalkylcarbonylalkyl, aminoalkylsulfonylalkyl, substituted aminoalkylsulfonylalkyl, alkoxycarbonylhydroxyalkyl, alkylcarbonylhydroxyalkyl, cycloalkylcarbonylhydroxyalkyl, heterocycloalkylcarbonyl-hydroxyalkyl, arylcarbonyl-hydroxyalkyl, aminocarbonyl-hydroxyalkyl, substituted aminocarbonylhydroxyalkyl, dialkoxyphosphoroxyalkyl, diphenyl-oxyphosphoroxyalkyl, arylalkyl, alkoxycarbonylamino, arylalkoxycarbonylamino, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, arylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl, arylalkylthioalkyl, arylalkylsulfinylalkyl or arylalkylsulfonylalkyl, where the substituted amino portion of the above R.sup.8 moieties is an amino group which is mono- or di-=substituted by alkyl, arylalkyl, alkanoyl, alkoxycarbonyl or arylalkoxycarbonyl, or disubstituted by C.sub.3 -C.sub.6 -alkylene which can be interrupted by an oxygen, sulfur or nitrogen atom, the nitrogen atom being unsubstituted or substituted with alkyl, phenylalkyl, alkanoyl or alkanoyloxy, with the proviso that R.sup.8 is not alkoxycarbonylamino or arylalkoxycarbonylamino when R.sup.7 is phenyl, benzyl or .alpha.-naphthyl;
• Y is a bivalent acyl radical of phenylglycine, cyclohexylglycine, phenylalanine, cyclohexylalanine, 4-fluorophenylalanine, 4-chlorophenylalanine, tyrosine, O-methyltyrosine, .alpha.-naphthylalanine or homophenylalanine, each of which may be N- or .alpha.-methylated and is lined with Z at the N-terminal;
• and Z is hydrogen or an acyl of a carboxylic acid,
• in the form of optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates or a pharmaceutically usable salt of such compound.