Age Inhibitors

Abstract

The invention relates to a compound having general formula I, wherein: X represents CH 2 , C═O, C═S or CHOH, X represents CH 2 , C═O, C═S or CHOH, R 1 represents an amino acid which is optionally substituted by one or more halogen atoms, preferably fluorine, or by one or more CF 3 groups and n=0.1 or 2, or X represents CH 2 , C═O, C═S, CHOH, R 1 represents a peptide containing two amino acids, each amino acid being optionally substituted by one or more halogen atoms, preferably fluorine, 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, XR 1 , 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, preferably fluorine, or one or more CF 3 groups; or the pharmaceutically-acceptable addition salts, isomers, enantiomers and diastereoisomers of said compound, mixtures thereof, and pharmaceutical or cosmetic compositions comprising same and the use thereof as an AGE-inhibitor drug that traps reactive carbonyl compounds.

1 . A compound of the following 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 X represents CH 2 , C═O, C═S or CHOH, R 1  represents a peptide containing two amino acids, each amino acid being optionally substituted by one or more halogen atoms, or one or more CF 3  groups, and n=0 or 1 or XR 1  represents PO 3 H or SO 3 H and n=0, 1 or 2; 
 R 2  represents H, XR 1 , a C 1 -C 6  alkyl group, a C 1 -C 6  aralkyl group or an aryl group, the alkyl, aralkyl and aryl groups being able to be substituted by NH 2 , a carboxylic group (COOH), one or more halogen atoms, or one or more CF 3  groups; 
 or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers of same, as well as mixtures of same, 
 with the exception of compounds
 wherein R 2  represents a hydrogen atom, X represents C═O, R 1  represents —NH—(CH 2 ) m —COOH and m=1, 2 or 3 and n=0, 1 or 2; 
 represented by the following formulas: 
 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and the compounds L-ornithyl-taurine, L-diaminobutyryl-taurine and L-diaminopropionyl taurine. 
     
     
         2 . A compound according to  claim 1 , wherein X represents C═O, CH 2  or C═S. 
     
     
         3 . A compound according to  claim 1 , wherein R 2  represents XR 1  or H. 
     
     
         4 . A compound according to  claim 1 , wherein R 1  represents an amino acid and n=0, 1 or 2. 
     
     
         5 . A compound according to  claim 1 , wherein said compound it is represented by the following general formula II: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  represents —NH—R 3 —(C═O) R 4  or 
 
       
         
           
           
               
               
           
         
         R 3  represents
 a C 1 -C 12  alkyl group, optionally substituted by one or more groups chosen among a halogen atom, a —CF 3 , phenyl, phenol, —COOH, amine or phenyl group substituted by one or more halogen atoms, or by one or more CF 3  groups; 
 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 , 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; 
         n=0, 1 or 2; 
         Y represents an oxygen or sulfur atom; 
         or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers of same, as well as mixtures of same. 
       
     
     
         6 . A compound according to  claim 1  or  5 , wherein n=0. 
     
     
         7 . A compound according to  claim 1 , wherein said compound is selected among 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers of same, as well as mixtures of same. 
     
     
         8 . A method for preventing the deterioration of proteins in foods comprising the addition to the food of a compound according to  claim 1  or  5 . 
     
     
         9 . A pharmaceutical or cosmetic composition comprising a compound according to claim,  1  or  5  and a pharmaceutically or cosmetically acceptable excipient. 
     
     
         10 . (canceled) 
     
     
         11 . A method according to  claim 19  or  20 , 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 chosen among a halogen atom, a —CF 3 , phenyl, phenol, —COOH, amine or phenyl group substituted by one or more halogen atoms, or by one or more CF 3  groups; 
 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 , 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; 
 n=0, 1 or 2; 
 Y represents an oxygen or sulfur atom; 
 or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers of same, as well as mixtures of same. 
 
     
     
         12 . A method according to  claim 19  or  20 , wherein said compound is selected among 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers of same, as well as mixtures of same. 
     
     
         13 - 15 . (canceled) 
     
     
         16 . A method according to  claim 19 , wherein the compound is administered by oral route. 
     
     
         17 . (canceled) 
     
     
         18 . A compound according to  claim 4  wherein the amino acid R 1  is selected among alanine, valine, isoleucine, proline, leucine, norleucine, phenylalanine or tert-leucine. 
     
     
         19 . A method for scavenging reactive carbonyl compounds, for inhibiting the formation of advanced glycation end-products, for the prevention and/or the treatment of a state or disease due to the formation of advanced glycation end-products or to the cross-linking of proteins, for the prevention and/or the treatment of the deleterious effects of the ageing of an organism, said effects being the formation of advanced glycation end-products or the cross-linking of proteins, or in a patient for the slowing or the stopping of the progression of complications resulting from diabetes, said complications resulting from the formation of advanced glycation end-products or from the cross-linking of proteins, for treating, preventing and/or slowing in a patient the progression of diseases chosen among rheumatoid polyarthritis, Alzheimer's disease, uremia, neurodegenerative diseases, atherosclerosis, microvascular and macrovascular complications of diabetes including diabetic retinopathy and renal failure due to diabetic nephropathy, microangiopathies and macroangiopathies, cataracts, amyloidosis associated with dialysis or with Alzheimer's disease, Parkinson's disease, gingivitis, cavities, bucco-dental conditions, diabetic ulcers, chronic renal failure, chronic renal dialysis, inflammatory diseases, age-related rheumatic disorders and porphyria and for treating early-stage cancers, comprising the administration of an effective amount of a compound of following 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 X represents CH 2 , C═O, C═S or CHOH, R 1  represents a peptide containing two amino acids, each amino acid being optionally substituted by one or more halogen atoms, or one or more CF 3  groups, and n=0 or 1 
 or XR 1  represents PO 3 H or SO 3 H and n=0, 1 or 2; 
 R 2  represents H, XR 1 , a C 1 -C 6  alkyl group, a C 1 -C 6  aralkyl group or an aryl group, the alkyl, aralkyl and aryl groups being able to be substituted by a NH 2 , a carboxylic group, one or more halogen atoms, or one or more CF 3  groups; 
 or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers of same, as well as mixtures of same, 
 with the exception of the compound 
 
       
         
           
           
               
               
           
         
       
       to a patient in need thereof. 
     
     
         20 . A method for treating the skin to reduce evidence of wrinkles and ageing and to restructure the epidermis and the papillary dermis comprising the administration of an effective amount of a compound of following 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 X represents CH 2 , C═O, C═S or CHOH, R, represents a peptide containing two amino acids, each amino acid being optionally substituted by one or more halogen atoms, or one or more CF 3  groups, and n=0 or 1 
 or XR 1  represents PO 3 H or SO 3 H and n=0, 1 or 2; 
 R 2  represents H, XR 1 , a C 1 -C 6  alkyl group, a C 1 -C 6  aralkyl group or an aryl group, the alkyl, aralkyl and aryl groups being able to be substituted by a NH 2 , a carboxylic group, one or more halogen atoms, or one or more CF 3  groups; 
 or the pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers of same, as well as mixtures of same, 
 with the exception of the compound 
 
       
         
           
           
               
               
           
         
       
       to a patient in need thereof.