DERIVATIVES OF AMINO ACIDS, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS

• Main Authors: HOEFKE, WOLFGANG, SCHNORRENBERG, GERD, GAIDA, WOLFRAM, LOSEL, WALTER, WIEDEMANN, INGRID, ROOS, OTTO
• Format: Patent
• Language: English; German
• Published: 11.01.1989
• Edition: 4
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The derivatives have the general formula in which R1 is H, phenyl, benzyl, phenethyl; R2 is H, acetyl, benzoyl, 3-sulphonamido-4-chlorobenzoyl, 3-sulphonamido-4-chloro-6-hydroxybenzoyl, 3-sulphonamido-4-chloro-5-[(furyl)amino]benzoyl, 2,3-dichloro-4-( beta -phenylacryloyl) phenoxyacetyl, pivaloyl, C1-C2-alkylaminocarbonyl, C1-C2-alkylaminothiocarbonyl, acyl or the radical A is the residue of one of the alpha -amino acids or R3 is hydrogen, C1-C4-alkyl, straight-chain or branched, C5-C7-cycloalkyl, it being possible for a phenyl ring to be fused on, phenyl, phenyl-C1-C4-alkyl, a hetero-C1-C4-alkyl radical where the heterocycle consists of a 5- or 6-membered ring with 1-2 of the hetero atoms O, S or N, R4 is hydrogen, C1-C4-alkyl, straight-chain or branched, phenyl, phenyl-C1-C4-alkyl or a hetero-C1-C4-alkyl radical where the heterocycle consists of a 5- or 6-membered ring with 1-2 of the hetero atoms O, S or N, or R3 and R4 together form with the N and the C atom a 5-, 6- or 7-membered ring which can be saturated or contain one double bond, or a 4-, 5- or 6-membered ring which contains one or two more of the hetero atoms O, S or N; R5 is OH, C1-C4- omega -hydroxyalkoxy, C1-C4-alkoxy, phenyl-C1-C4-alkoxy, C1-C4-alkylamino, (C1-C4)2-dialkylamino, one of the groups or an alpha -amino acid which is linked in the manner of a peptide to the CO group of the molecule; R6 is C1-C4-alkyl, C1-C3-alkenyl, C1-C3-alkynyl, straight-chain or branched, hydroxyl, nitro, amino, C1-C4-alkoxy, mercapto, C1-C4- alkylthio, hydroxy-C1-C4-alkyl,mercapto-C1-C4-alkyl, F, Cl, Br, amino-C1-C4-alkyl, sulphonamido, methylenedioxy, fluoro-C1-C4-alkyl, chloro-C1-C4-alkyl, bromo-C1-C4-alkyl, cyano or trifluoromethyl; R7 is hydrogen or methyl; R8 is C1-C4-alkyl, straight-chain or branched, where the alkyl radical can be substituted by F, Cl, Br, CF3, phenyl or pyridyl; X, Y and Z are O, S, CR10, CHR10, with the proviso that only one of the radicals X, Y and Z can be O, S, and one or two radicals X, Y and Z can be NR9; R9 is hydrogen or C1-C4-alkyl, straight-chain or branched; R10 is hydrogen or, together with a vicinal radical R10, a phenyl ring or, for m and n = 1, the dihydro form thereof with the double bond in conjugation with the C-terminal carboxyl group and m and n are each 0, 1 or 2, where the total of m and n is 1 or 2, and are strong inhibitors of angiotensin I converting enzyme and are intended for use as hypotensive agents.