Age inhibitors

Patent metadata

Field	Value
Publication number	US-9512176-B2
Application number	US-201213437491-A
Country	US
Kind code	B2
Filing date	Apr 2, 2012
Priority date	Mar 31, 2005
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

The invention relates to a compound having general formula I, wherein: X represents CH 2 , C═O, C═S or CHOH, R 1 represents an amino acid optionally substituted by one or more halogen atoms, or by one or more CF 3 groups and n=0.1 or 2, or R 1 represents a peptide containing two amino acids, each amino acid being optionally substituted by one or more halogen atoms, or by one or more CF 3 groups and n=0 or 1, or XR 1 represent PO 3 H or SO 3 H and n=0.1 or 2; R 2 represents H, XR1, an alkyl group at C 1 -C 6 , an aralkyl group at C 1 -C 6 or an aryl group, whereby the alkyl, aralkyl and aryl groups can be substituted by an amine NH 2 , a carboxylic group COOH, one or more halogen atoms.

First claim

The invention claimed is:

1. A method for treating a patient suffering from a disease or condition associated with reactive α-dicarbonyl compounds, the method comprising scavenging methylglyoxyl comprising the administration of an effective amount of a compound of following general formula I:

wherein:
X represents CH 2 , C═O, or C═S;
R 1 represents
NH—R 3 —(C═O)R 4 or

wherein
R 3 represents
a C 1 -C 12 alkyl group optionally substituted by one or more groups selected from the group consisting of a halogen atom, a —CF 3 , a phenyl, a phenol, a —COOH, an amine, and a phenyl group substituted by one or more halogen atoms or by one or more CF 3 groups; or
a phenyl group, optionally, substituted by an amine, an OH group, one or more halogen atoms, or one or more CF 3 groups; and

R 4 represents OH, NH 2 , or a C 1 -C 30 alkoxy;
n=0; and
R 2 represents H, COR 1 , or a C 1 -C 6 alkyl group optionally substituted by one or more halogen atoms, or by one or more CF 3 groups;
or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers thereof and mixtures thereof,
to a patient in need thereof, and wherein the disease or condition is selected from the group consisting of cataract, uremia, artheriosclerosis, Alzheimer's disease, Parkinson's disease, diabetic ulcers, type 2 diabetes, diabetic retinopathy, diabetic nephropathy, microangiopathies, and macroangiopathies.

2. The method according to claim 1 , wherein said compound is represented by the following general formula II:

wherein:
R 1 represents NH—R 3 —(C═O)R 4 or

wherein
R 3 represents
a C 1 -C 12 alkyl group, optionally substituted by one or more groups selected from the group consisting of a halogen atom, a —CF 3 , a phenyl, a phenol, a —COOH, an amine, and a phenyl group substituted by one or more halogen atoms, or by one or more CF 3 groups; or
a phenyl group, optionally substituted by an amine, an OH group, one or more halogen atoms, or one or more CF 3 groups; and

R 4 represents OH, NH 2 , or a C 1 -C 30 alkoxy;
R 2 represents H, COR 1 , or a C 1 -C 6 alkyl group optionally substituted by one or more halogen atoms, or by one or more CF 3 groups; and
Y represents an oxygen or sulfur atom;
or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers thereof and mixtures thereof.

3. The method according to claim 1 , wherein said compound is selected among

or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers thereof and mixtures thereof.

4. The method according to claim 1 , wherein R 1 is alanine, valine, isoleucine, proline, leucine, norleucine, phenylalanine or tert-leucine.

5. A method for treating the skin of a patient in order to provide an antiaging or restructuring effect on the epidermis and the papillary dermis, the method comprising scavenging methylglyoxyl comprising the administration of an effective amount of a compound of the following general formula (I):

wherein:
X represents CH 2 , C═O, C═S or CHOH;
R 1 represents
NH—R 3 —(C═O)R 4 or

wherein
R 3 represents
a C 1 -C 12 alkyl group optionally substituted by one or more groups selected from the group consisting of a halogen atom, a —CF 3 , a phenyl, a phenol, a —COOH, an amine, and a phenyl group substituted by one or more halogen atoms or by one or more CF 3 groups; or
a phenyl group, optionally, substituted by an amine, an OH group, one or more halogen atoms, or one or more CF 3 groups; and

R 4 represents OH, NH2, or a C 1 -C 30 alkoxy;
n=0; and
R 2 represents H, COR 1 , or C 1 -C 6 alkyl group optionally substituted by one or more halogen atoms, or by one or more CF 3 groups;
or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers thereof and mixtures thereof,
to a patient in need thereof.

6. The method according to claim 1 , wherein the compound has the following formula:

7. A method for treating a patient suffering from a disease or condition associated with reactive α-dicarbonyl compounds, the method comprising scavenging methylglyoxyl comprising the administration of an effective amount of a compound selected from the group consisting of

or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers thereof and mixtures thereof, and wherein the disease or condition is selected from the group consisting of cataract, uremia, artheriosclerosis, Alzheimer's disease, Parkinson's disease, type 2 diabetes, diabetic retinopathy, diabetic nephropathy, microangiopathies, and macroangiopathies.

8. The method of claim 7 , wherein the compound is selected from the group consisting of

9. A method for treating a patient suffering from a disease or condition selected from the group consisting of cataract, uremia, artheriosclerosis, Alzheimer's disease, Parkinson's disease, diabetic ulcers, type 2 diabetes, diabetic retinopathy, diabetic nephropathy, microangiopathies, and macroangiopathies, the method comprising administering to a patient in need thereof an effective amount of a compound of following general formula I:

wherein:
X represents CH 2 , C═O, or C═S;
R 1 represents
NH—R 3 —(C═O)R 4 or

Assignees

• Potier Pierre
• Potier Guy Jean Marie
• Zelveyan Marie-Claude Denise Michele
• Magnan Catherine Marie Germaine
• Drion Odette
• Sasaki Nobumichi Andre
• Achab Garcia Alvarez Maria Concepcion
• Wang-Zhu Qian
• Ermolenko Lioudmila
• Bakala Joanna
• Franck Gisele
• Bakrim Nhiri Naima
• Centre Nat Rech Scient

Inventors

• Potier Pierre
• Sasaki Nobumichi Andre
• Achab Garcia Alvarez Maria Concepcion
• Wang-Zhu Qian
• Ermolenko Lioudmila
• Bakala Joanna
• Franck Gisele
• Bakrim Nhiri Naima

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P27/12

  for cataracts · CPC title