Patent CA-1328333-C (CA)
Title: Amino acid derivatives
Inventor: BRANCA QUIRICO
IPC: C07C237/00
Filed: 1989-02-16
Granted: 1994-04-05
Abstract: Abstract The compounds of the formula           I     wherein R1 signifies hydrogen or methyl, R2 signifies ethyl, propyl, isopropyl, imidazol-2-yl, imidazol-4-yl, pyrazol-3-yl, thiazol-4-yl, thien-2-yl or t-butoxy, R3 signifies isobutyl. cyclohexylmethyl or benzyl, R4 and R5 each independently signify hydrogen, alkanoyl. which is optionally mono- or multiply-substituted by amino, monoalkylamino, dialkylamino, alkanoylamino, alkanoyloxyamino, carboxy, alkoxy or hydroxy, or an O-protecting group or together signify a cyclic O-protecting group, R6 signifies one of the groups          and                (a)                            (b) and A signifies one of the groups    (c)   and -Y-Z   (d), wherein D signifies a methyne group or a nitrogen atom, R7 signifies alkyl, aryl or arylalkyl and R8 signifies hydrogen, alkyl, aryl or arylalkyl or R7 and R8 together with the two atoms to which they are attached signify aryl, heteroaryl, cycloalkenyl or heterocycloalkenyl, R9 signifies hydrogen or alkyl and R10 and R11 each independently signify alkyl, aryl, arylalkyl, cycloalkyl or the group (e) or, together with the carbon atom to which they are attached, cycloalkyl or heterocycloalkyl, with the proviso that, where R9 signifies alkyl, R10 and R11 also signify alkyl, the dotted line can signify and additional bond, R12 signifies phenyl, substituted phenyl, benzyl or naphthyl and R13 signifies hydrogen, alkoxycarbonylalkyl, alkyl-carbonylalkyl, cycloalkylcarbonylalkyl, heterocyclo-alkylcarbonylalkyl, arylcarbonylalkyl, aminocarbonyl-hydroxyalkyl, alkylcarbonylhydroxyalkyl, cycloalkyl-carbonylhydroxyalkyl, heterocycloalkylcarbonylhydroxy-alkyl, arylcarbonylhydroxyalkyl, aminocarbonylhydroxy-alkyl, substituted aminocarbonylhydroxyalkyl, dialkoxyphosphoroxyalkyl, diphenyloxyphosphoroxyalkyl, arylalkyl, alkoxycarbonylamino, arylalkoxycarbonyl-amino, alkylthioalkyl, alkylsulphinylalkyl or alkyl-sulphonylalkyl, with the proviso that R13 can not signify alkoxycarbonylamino or arylalkoxycarbonylamino when R12 signifies phenyl, benzyl or .alpha.-naphthyl, Y signifies the bivalent residue of optionally N- and/or .alpha.-methylated phenylalanine, cyclohexylalanine, tyrosine, O-methyltyrosine, .alpha.-naphthylalanine or homophenylalanine linked with Z at the N-terminal, Z signifies acyl, X signifies an oxygen or sulphur atom or the group -NH- and R14 signifies hydrogen, alkyl, cycloalkyl, arylalkyl, cycloalkylalkyl, alkylcarbonyl, arylcarbonyl or arylalkylcarbonyl, in the form of optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates as well as pharmaceutically usable salts of these compounds, have an inhibitory activity on the natural enzyme renin and can accordingly be used in the form of pharmaceutical preparations for the control or prevention of high blood pressure and cardiac insufficiency.  They can be manufactured from the corresponding, non-acylated dihydroxy derivatives and optional subsequent O-alkanolylation or conversion into O-protected derivatives.