Aminoacid derivatives and their therapeutic applications
AssigneeSociete Civile Bioprojet
InventorsBernard Roques, Jean-Charles Schwartz, Jeanne-Marie Lecomte
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Abstract
This invention relates to aminoacid derivatives, and compositions containing the same and having enkephalinase-inhibiting, antalgic, antidiarrhea and hypotensive activities, of the formula ##STR1## whose variables are as set forth herein, for example ##STR2##
Claims17
A compound selected from the group consisting of:
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]-glycine methyl ester;
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]-glycine;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]-L-alanine methyl ester;
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]-L-alanine;
- O-benzyl,N-[(R,S)-3-mercapto-2-benzyl-propionyl]-L-serine;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine benzyl ester;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine p.fluorobenzyl ester;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine 2,2,2-trifluoroethyl ester;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine benzylamide;
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]glycine benzyl ester;
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]-glycine 2,2,2-trifluoroethyl ester;
- N-[(R,S)-3-phenylacetylthio-2-benzyl-propionyl]-glycine benzyl ester;
- and
- N-[(R,S)-3-benzylthio-2-benzyl-propionyl]-glycine benzyl ester.
Therapeutic composition having particularly enkephalinase-inhibiting, antalgic and anti-diarrhea activities, comprising, as active ingredient a therapeutically effective amount of a compound selected from the group consisting of:
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]-glycine;
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]-L-alanine;
- O-benzyl,N-[(R,S)-3-mercapto-2-benzyl-propionyl]-L-serine;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine benzyl ester;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine p.fluorobenzyl ester;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine 2,2,2-trifluoroethyl ester;
- N-[(R,S)-3-acetylthio-2-benzyl-propionyl]glycine benzylamide;
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]glycine benzyl ester;
- and
- N-[(R,S)-3-mercapto-2-benzyl-propionyl]-glycine 2,2,2-trifluoroethyl ester;
- in admixture with a therapeutically acceptable excipient.
##STR26##
##STR28##
Aminoacid derivatives having the following general formula:
- ##STR30## in which:
- A is carbonyl;
- B is amino;
- R.sub.1 is selected from phenyl;
- and phenyl mono- or polyhalosubstituted;
- n is 1;
- R.sub.2 is selected from:
- hydrogen;
- methyl and benzyloxymethyl;
- R.sub.3 is a group selected from --OR.sub.4 and --NHR.sub.4 in which R.sub.4 is selected from:
- hydrogen;
- straight- and branched-chain C.sub.1-8 alkyl;
- straight and branched-chain C.sub.1-8 alkyl mono- or poly-halosubstituted;
- phenyl(C.sub.1-4 alkyl);
- and phenyl(C.sub.1-4 alkyl) mono- or polyhalosubstituted on the phenyl group;
- Y is --NH-- or --CH.sub.2 --;
- X is selected from:
- C.sub.1-2 alkyl substituted with mercapto;
- mercapto;
- aliphatic (C.sub.1-4 acyl)thio;
- benzoylthio;
- and phenyl (C.sub.1-4 alkyl) carbonylthio,
- and their addition salts with pharmaceutically acceptable acids and bases.
Therapeutic composition having particularly enkephalinase-inhibiting, antalgic and anti-diarrhea activities, comprising, as active ingredient a therapeutically effective amount of a compound selected from the group consisting of the compounds having the formula:
- ##STR31## in which:
- A is carbonyl;
- B is amino;
- R.sub.1 is selected from phenyl;
- and phenyl mono- or polyhalosubstituted;
- n is 1;
- R.sub.2 is selected from:
- hydrogen;
- methyl;
- and benzyloxymethyl;
- R.sub.3 is a group selected from --OR.sub.4 and --NHR.sub.4 in which R.sub.4 is selected from:
- hydrogen;
- straight- and branched-chain C.sub.1-8 alkyl;
- straight and branched-chain C.sub.1-8 alkyl mono- or polyhalosubstituted;
- phenyl(C.sub.1-4 alkyl);
- and phenyl(C.sub.1-4 alkyl) mono- or polyhalosubstituted on the phenyl group;
- Y is --NH-- or --CH.sub.2 --;
- X is selected from:
- hydrogen;
- C.sub.1-2 alkyl substituted with mercapto;
- mercapto;
- aliphatic (C.sub.1-4 acyl) thio;
- benzoylthio;
- and phenyl (C.sub.1-4 alkyl) carbonylthio;
- and their addition salts with pharmaceutically acceptable acids and bases, together with a therapeutically acceptable carrier.
Aminoacid derivatives having the following general formula:
- ##STR32## in which:
- A is amino;
- B is carbonyl;
- R.sub.1 is selected from phenyl;
- and phenyl mono- or polyhalosubstituted;
- n is 1;
- R.sub.2 is selected from:
- hydrogen;
- straight- and branched C.sub.1-6 alkyl;
- benzyl;
- and benzyloxyalkyl;
- R.sub.3 is a group selected from --OR.sub.4 and --NHR.sub.4 in which R.sub.4 is selected from:
- hydrogen;
- straight- and branched-chain C.sub.1-8 alkyl;
- straight and branched-chain C.sub.1-8 alkyl mono- or poly-halosubstituted;
- phenyl(C.sub.1-4 alkyl);
- and phenyl(C.sub.1-4 alkyl) mono- or polyhalosubstituted on the phenyl group;
- Y is a group selected from --NH-- or --CH.sub.2 --;
- X is selected from:
- hydrogen;
- C.sub.1-2 alkyl substituted with a substituent selected from alkoxycarbonyl, carboxy, mercapto, aliphatic (C.sub.1-4 acyl)thio, and benzoylthio;
- mercapto;
- aliphatic (C.sub.1-4 acyl)thio;
- benzoylthio;
- and phenyl (C.sub.1-4 alkyl) carbonylthio;
- and their addition salts with pharmaceutically acceptable acids and bases.
Dependencies are inferred from the claim text.