Amino acid derivatives having renin inhibiting activity
AssigneeHoffmann-La Roche Inc.
InventorsQuirico Branca, Werner Neidhart, Henri Ramuz, Heinz Stadler, Wolfgang Wostl
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Abstract
The compounds of the formula ##STR1## in the form of optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates as well as pharmaceutically usable salts thereof inhibit the activity of the natural enzyme renin and can accordingly be used in the form of pharmaceutical preparations in the control or prevention of high blood pressure and cardiac insufficiency.
Claims20
A compound of the formula:
- ##STR13## wherein:
- R.sup.2 is imidazol-4-yl, R.sup.3 is cyclohexylmethyl or 4,4-difluorocyclohexylmethyl, R.sup.5 and R.sup.7 each are hydroxy or aminomethylcarbonyloxy, R.sup.12 and R.sup.13 together with the carbon atom to which they are attached are cyclopropyl or cyclobutyl, R.sup.14 is phenyl and R.sup.15 is C.sub.1 -C.sub.4 -alkylcarbonylmethyl, heterocycloalkylcarbonylmethyl, substituted aminocarbonylmethyl, C.sub.1 -C.sub.4 alkylsulphonylmethyl, C.sub.3 -C.sub.6 -cycloalkylsulphonylmethyl, C.sub.3 -C.sub.6 -cycloalkyl-C.sub.1 -C.sub.4 -alkylsulphonylmethyl, substituted amino-C.sub.1 -C.sub.4 -alkylcarbonylmethyl, heterocycloalkylcarbonyloxy, amino-C.sub.1 -C.sub.4 -alkylsulphonylmethyl or substituted amino-C.sub.1 -C.sub.4 -alkylsulphonylmethyl.
(S)-.alpha.-(S)-.alpha.-(tert-Butylsulphonyl)m ethyl!hydrocinnamamido!-N-(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2, 3-dihydroxypropyl!-5-cyanoimidazole-4-propionamide.
(S)-.alpha.-(S)-.alpha.-(t ert-Butylsulphonyl)methyl!hydrocinnamamido!-N-(1S,2R,3S)-3-cyclopropyl-1-( p-fluorobenzyl)-2,3-dihydroxypropyl!imidazole-4-propionamide.
(S)-N-(1S,2R,3S)-3-Azido-1-(cyclohex ylmethyl)-3-cyclopropyl-2-hydroxypropyl!-.alpha.-(S)-.alpha.-(tert-butylsu lphonyl)methyl!-hydrocinnamamido!imidazole-4-propionamide.
(S)-.alpha.-(S)-.alpha.-(tert-butylsulphonyl)methyl! hydrocinnamamido!-N-(1S,2R)-1-(cyclohexylmethyl)-2-(R or S)-3-cyclopropyl-2-oxo-5-oxazolidinyl!-2-hydroxyethyl!-imidazole-4-propion amide.
(S )-.alpha.-(S)-.alpha.-(tert-butylsulphonyl)methyl!hydrocinnamamido!-N-(1 S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-3-fluoro-2-hydroxypropyl!imidaz ole-4-propionamide.
(S or R)-2-(S)-1-(1S,2R,3S)-1-(cyclohexyl-methyl)-3-cyclopropyl-2,3-dihydrox ypropyl!carbamoyl!-2-imidazol-4-ylethyl!carbamoyl!-3-phenylpropanesulphonic acid guanidine salt.
N-(S)-1-(1S,2R ,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl!carbamoyl!-2-im idazol-4-ylethyl!-indole-2-carboxamide.
(S)-N-(1S,2R,3S)-1-(cyclohexylmeth yl)-3-cyclopropyl-2,3-dihydroxy-propyl!-.alpha.-(2,2-dibenzylacetamido)imid azole-4-propionamide.
N-(S)-1-(1S,2R ,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl!carbamoyl!-2-im idazol-4-ylethyl!-2-benzimidazolecarboxamide.
(1R,2S)-1-(S)-1-.about.(5)-1-acetyl-.alp ha.-(S)-.alpha.-(tert-butylsulphonyl)methyl!imidazole-4-propionamido!-2-cy clohexylethyl!-2-cyclopropylethylene diacetate.
(1S,2R,3S)-3-(S)-.alpha.-(S)-.alpha.-(te rt-butylsulphonyl)methyl!hydrocinnamamido!imidazole-4-propionamido!-4-cyclo hexyl-1-cyclopropyl-2-hydroxybutyl o-aminobenzoate.
(1R,2S)-1-(S)-1-(S)-.alpha.-(S)-.alpha.-(te rt-butylsulphonyl)methyl!hydrocinnamamido!imidazole-4-propionamido!-2-cyclo hexylethyl!-2-cyclopropylethylene dicyclopropane carboxylate.
Ethyl 4-(S)-2-(S)-.alpha.-(tert-butylsulphonyl)methyl!hydrocinnamamido!-2-( 1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl!carbamoyl! ethyl!imidazole-1-carboxylate.
Dependencies are inferred from the claim text.