US 5,599,951 AGranted

Amino acid derivatives, the process for their preparation and their applications to therapy

AssigneeSociete Civile Bioprojet

InventorsJean-Christophe Plaquevent, Denis Danvy, Thierry Monteil, Claude Gros, Jean-Charles Schwartz, Jeanne-Marie LeComte, Helene Greciet, Lucette Duhamel, Pierre Duhamel

Life of this patent

Estimating the term…

Abstract

Amino acid derivatives of formula (Ia) and (Ib) and prodrugs thereof containing a group responsible for chelating the zinc atom of enkephalinase and angiotensin convertase enzymes are disclosed as inhibitors of these enzymes.

Claims3

Dependent claims

An amino acid derivative corresponding to the general formula:

##STR53## wherein ##STR54## wherein Z and Y are O and n=1 or 2 R.sub.2 represents a hydrogen atom, a lower alkyl group, a lower hydroxyalkylene group, a phenyl group, a lower phenylalkylene group, a lower hydroxyphenylalkylene group, a lower aminoalkylene group, a lower guanidinoalkylene group, a lower mercaptoalkylene group, a lower indolylalkylene group, a lower carbamylalkylene group, a lower alkylthio lower alkylene group, a lower imidazolylalkylene group, a lower carboxylalkylene group or one of the following groups:
##STR55## wherein Z', Y' and n have the meanings defined below:
______________________________________ Z' Y' n ______________________________________ O O 1 O O 2 O CH.sub.2 1 CH.sub.2 CH.sub.2 1 CH.sub.2 CH.sub.2 2 ______________________________________
X designates the group responsible for chelating the zinc atom of the enzymes (enkephalinase and ACE) selected from the group consisting of a mercaptomethyl, hydroxamic acid, and an N-carboxylalkyl of the formula ##STR56## wherein R.sub.3 represents a benzyl lower alkyl radical or a benzyl lower alkoxy radical, or phosphorated derivatives of formula ##STR57##

1 more element

An amino acid derivative chosen from:

N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]glycine or its optically pure forms,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-alanine or its optically pure forms,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-2-aminobutyric acid,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-norvaline,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-norleucine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-leucine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-tryptophan,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-phenylalanine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-tyrosine,
N-(S)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-serine
N-(S)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(S)-methionine,
N-(S)-[1-oxo-2-(mercaptomethyl)-3-(3,4-methylenedioxy phenyl)propyl]-(RS)-3-(3,4-methylenedioxy phenyl)-analine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-ethylenedioxy phenyl)propyl]-glycine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(3,4-ethylenedioxy phenyl)propyl]-(S)-alanine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(2,3-methylenedioxy phenyl)propyl]-glycine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(4-phenoxy phenyl)propyl]-glycine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(4-phenoxy phenyl)propyl]-(S)-alanine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(4-phenyl phenyl)propyl]-glycine or its optically pure forms,
N-(R)[1-oxo-2-(mercaptomethyl)-3-(4-phenyl phenyl)propyl]-(S)-alanine or its optically pure forms,
N-(R)[1-oxo-2-(mercaptomethyl)-3-(4-phenyl phenyl)propyl]-(S)-leucine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(5'-indanyl)propyl]-glycine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(5'-indanyl)propyl]-(S)-alanine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(2',3'-dihydro-5'-benzofuranyl)propyl]-g lycine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(2',3'-dihydro-5'-benzofuranyl)propyl]-( S)-alanine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(4-methoxy phenyl)propyl]-glycine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(4-methoxy phenyl)propyl]-(S)-alanine,
N-(S)-[1-oxo-2-(mercaptomethyl)-3-(4-methoxy phenyl)propyl]-glycine,
N-(S)-[1-oxo-2-(mercaptomethyl)-3-(4-methoxy phenyl)propyl]-(S)-alanine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(4-ethoxy phenyl)propyl]-glycine,
N-(RS)-[1-oxo-2-(mercaptomethyl)-3-(4-ethoxy phenyl)propyl]-(S)-alanine,
N-(E)-[1-oxo-2-(mercaptomethyl)-2-ene-3-phenyl propyl]-(S)-alanine,
N-(E)-[1-oxo-2-(mercaptomethyl)-2-ene-3-phenyl propyl]-(S)-norvaline,
N-(E)-[1-oxo-2-(mercaptomethyl)-2-ene-3-phenyl propyl]-(S)-norleucine,
N-(E)-[1-oxo-2-(mercaptomethyl)-2-ene-3-phenyl propyl]-(RS)-3-(3,4-methylenedioxy phenyl)-alanine,
N-(Z)-[1-oxo-2-(mercaptomethyl)-2-ene-3-(3,4-methylenedioxy phenyl)propyl]-glycine,
N-[N-(RS)-(1-carboxy pentyl)-(RS)-3-(3,4-methylenedioxy phenyl)alanyl]-glycine hydrochloride,
N-[N-(RS)-(1-carboxy-2-phenyl ethyl)-(S)-phenylalanyl]-glycine hydrochloride,
N-[N-(RS)-(1-carboxy-2-phenyl ethyl)-(RS)-3-(3,4-methylenedioxy phenyl)alanyl]-glycine hydrochloride,
N-(RS)-[2-dihydroxyphosphinylmethyl-1-oxo-3-(3,4-methylenedioxy phenyl)propyl]-(S)-alanine or its calcium monosalt,
N-(RS)-[2-dihydroxyphosphinylmethyl-1-oxo-3-(3,4-methylenedioxy phenyl)propyl]-glycine or its calcium monosalt,
N-(RS)-[2-(dihydroxyphosphinyl)methyl-1-oxo-3-(4-phenyl phenyl)propyl]-(S)-alanine or its calcium monosalt,
N-(RS)-[2-(dihydroxyphosphinyl)methyl-1-oxo-3-(4-phenyl phenyl)propyl]-glycine or its calcium monosalt.

39 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/422,652Filed 14 Apr 1995 · continuation
Priority: FR 89 1214215 Sep 1989
Granted: 4 Feb 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 307/79
Benzo [b] furans; Hydrogenated benzo [b] furans: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to…
C07C 323/60
Having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton: with the carbon atom of at least one of the…
C07D 317/60
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring: radicals…
C07D 319/18
Condensed with one six-membered ring: ethylenedioxybenzenes, not substituted on the hetero ring

Family

Serial689,238Parent of this continuation · filed 13 Jun 1991
Serial103,156Parent of this continuation · filed 9 Aug 1993
US 5,599,951 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

08/422,652Filed 14 Apr 1995 · continuation

Priority

FR 89 1214215 Sep 1989

Granted

4 Feb 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 307/79
Benzo [b] furans; Hydrogenated benzo [b] furans: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to…
C07C 323/60
Having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton: with the carbon atom of at least one of the…
C07D 317/60
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring: radicals…
C07D 319/18
Condensed with one six-membered ring: ethylenedioxybenzenes, not substituted on the hetero ring