Aminoacid derivatives and their therapeutic applications

Claim 2

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.

Claim 3

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.

Claim 4

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.

Claim 5

Therapeutic composition as claimed in claim 2, in unit dosage form, each unit dose containing 0.5-100 mg active ingredient.

Claim 6

##STR26##

Claim 7

##STR26##

Claim 8

Therapeutic composition as claimed in claim 2, wherein said compound is ##STR27##

Claim 9

##STR28##

Claim 10

##STR28##

Claim 11

Therapeutic composition as claimed in claim 2, wherein said compound is ##STR29##

Claim 12

Aminoacid derivatives having the following general formula: ##STR30## in which: A is carbonyl; B is amino; R 1 is selected from phenyl; and phenyl mono- or polyhalosubstituted; n is 1; R 2 is selected from: hydrogen; methyl and benzyloxymethyl; R 3 is a group selected from --OR 4 and --NHR 4 in which R 4 is selected from: hydrogen; straight- and branched-chain C 1-8 alkyl; straight and branched-chain C 1-8 alkyl mono- or poly-halosubstituted; phenyl(C 1-4 alkyl); and phenyl(C 1-4 alkyl) mono- or polyhalosubstituted on the phenyl group; Y is --NH-- or --CH 2 --; X is selected from: C 1-2 alkyl substituted with mercapto; mercapto; aliphatic (C 1-4 acyl)thio; benzoylthio; and phenyl (C 1-4 alkyl) carbonylthio, and their addition salts with pharmaceutically acceptable acids and bases.

Claim 13

Aminoacid derivatives having the following general formula: ##STR30## in which: A is carbonyl; B is amino; R 1 is selected from phenyl; and phenyl mono- or polyhalosubstituted; n is 1; R 2 is selected from: hydrogen; methyl and benzyloxymethyl; R 3 is a group selected from --OR 4 and --NHR 4 in which R 4 is selected from: hydrogen; straight- and branched-chain C 1-8 alkyl; straight and branched-chain C 1-8 alkyl mono- or poly-halosubstituted; phenyl(C 1-4 alkyl); and phenyl(C 1-4 alkyl) mono- or polyhalosubstituted on the phenyl group; Y is --NH-- or --CH 2 --; X is selected from: C 1-2 alkyl substituted with mercapto; mercapto; aliphatic (C 1-4 acyl)thio; benzoylthio; and phenyl (C 1-4 alkyl) carbonylthio, and their addition salts with pharmaceutically acceptable acids and bases.

Claim 14

Compounds according to claim 8, wherein R 2 is hydrogen.

Claim 15

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 1 is selected from phenyl; and phenyl mono- or polyhalosubstituted; n is 1; R 2 is selected from: hydrogen; methyl; and benzyloxymethyl; R 3 is a group selected from --OR 4 and --NHR 4 in which R 4 is selected from: hydrogen; straight- and branched-chain C 1-8 alkyl; straight and branched-chain C 1-8 alkyl mono- or polyhalosubstituted; phenyl(C 1-4 alkyl); and phenyl(C 1-4 alkyl) mono- or polyhalosubstituted on the phenyl group; Y is --NH-- or --CH 2 --; X is selected from: hydrogen; C 1-2 alkyl substituted with mercapto; mercapto; aliphatic (C 1-4 acyl) thio; benzoylthio; and phenyl (C 1-4 alkyl) carbonylthio; and their addition salts with pharmaceutically acceptable acids and bases, together with a therapeutically acceptable carrier.

Claim 16

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 1 is selected from phenyl; and phenyl mono- or polyhalosubstituted; n is 1; R 2 is selected from: hydrogen; methyl; and benzyloxymethyl; R 3 is a group selected from --OR 4 and --NHR 4 in which R 4 is selected from: hydrogen; straight- and branched-chain C 1-8 alkyl; straight and branched-chain C 1-8 alkyl mono- or polyhalosubstituted; phenyl(C 1-4 alkyl); and phenyl(C 1-4 alkyl) mono- or polyhalosubstituted on the phenyl group; Y is --NH-- or --CH 2 --; X is selected from: hydrogen; C 1-2 alkyl substituted with mercapto; mercapto; aliphatic (C 1-4 acyl) thio; benzoylthio; and phenyl (C 1-4 alkyl) carbonylthio; and their addition salts with pharmaceutically acceptable acids and bases, together with a therapeutically acceptable carrier.

Claim 17

Aminoacid derivatives having the following general formula: ##STR32## in which: A is amino; B is carbonyl; R 1 is selected from phenyl; and phenyl mono- or polyhalosubstituted; n is 1; R 2 is selected from: hydrogen; straight- and branched C 1-6 alkyl; benzyl; and benzyloxyalkyl; R 3 is a group selected from --OR 4 and --NHR 4 in which R 4 is selected from: hydrogen; straight- and branched-chain C 1-8 alkyl; straight and branched-chain C 1-8 alkyl mono- or poly-halosubstituted; phenyl(C 1-4 alkyl); and phenyl(C 1-4 alkyl) mono- or polyhalosubstituted on the phenyl group; Y is a group selected from --NH-- or --CH 2 --; X is selected from: hydrogen; C 1-2 alkyl substituted with a substituent selected from alkoxycarbonyl, carboxy, mercapto, aliphatic (C 1-4 acyl)thio, and benzoylthio; mercapto; aliphatic (C 1-4 acyl)thio; benzoylthio; and phenyl (C 1-4 alkyl) carbonylthio; and their addition salts with pharmaceutically acceptable acids and bases.

Claim 18

Aminoacid derivatives having the following general formula: ##STR32## in which: A is amino; B is carbonyl; R 1 is selected from phenyl; and phenyl mono- or polyhalosubstituted; n is 1; R 2 is selected from: hydrogen; straight- and branched C 1-6 alkyl; benzyl; and benzyloxyalkyl; R 3 is a group selected from --OR 4 and --NHR 4 in which R 4 is selected from: hydrogen; straight- and branched-chain C 1-8 alkyl; straight and branched-chain C 1-8 alkyl mono- or poly-halosubstituted; phenyl(C 1-4 alkyl); and phenyl(C 1-4 alkyl) mono- or polyhalosubstituted on the phenyl group; Y is a group selected from --NH-- or --CH 2 --; X is selected from: hydrogen; C 1-2 alkyl substituted with a substituent selected from alkoxycarbonyl, carboxy, mercapto, aliphatic (C 1-4 acyl)thio, and benzoylthio; mercapto; aliphatic (C 1-4 acyl)thio; benzoylthio; and phenyl (C 1-4 alkyl) carbonylthio; and their addition salts with pharmaceutically acceptable acids and bases.

Claim 19

Compounds according to claim 11 wherein R 2 is hydrogen.

Claim 20

Compounds according to claim 11 wherein Y is NH.

Claim 21

Compounds according to claim 11 wherein Y is CH 2 and X is SH.

Claim 22

Therapeutic composition having particularly enkephalinase-inhibiting, antalgic and anti-diarrhea activities, comprising, as active ingredient a therapeutically effective amount of a compound according to claim 11, together with a therapeutically acceptable carrier.

Claim 23

A compound as claimed in claim 1, which is N-[(R,S)-3-mercapto-2-benzyl-propionyl]-glycine.

Claim 24

A compound according to claim 1, which is N-[(R,S)-3-mercapto-2-benzyl-propionyl]-L-alanine.