Method for synthesizing kpv tripeptide diamide derivates

Abstract

The object of the invention is to provide an improved method for synthesizing a KPV tripeptide diamide derivate having the formula (I) such as defined in the specification. The synthesis method according can be implemented with any of the stereoisomers of each of the Lysine (K), Proline (P) or Valine (V) amino acid residues.

1 . A KPV tripeptide diamide derivative or salt thereof represented by the following formula (IA): 
       
         
           
           
               
               
           
         
         wherein: 
         a) R1, R′1 and R″1 represent, independently from each other, a hydrogen atom or
 a linear or branched C1-C22 alkyl moiety, optionally interrupted by a heteroatom, 
 C4-C10 cycloalkyl moiety, 
 a linear or branched C1-C22 polyfluoroalkyl or perfluoroalkyl moiety, 
 an aryl moiety optionally substituted by one or more halogen atoms or one or more linear or branched C1-C4 alkyl moieties, 
 an aralkyl moiety, 
 or R1 and R′1 could form with C(R″1) a saturated ring with from 3 to 7 atoms, optionally substituted by one or more linear or branched C1-C4 alkyl moieties and/or optionally containing a heteroatom, 
 hydrogen, 
 
         with the proviso that the R1(R′1)(R″1)CO group does not represent an amino acid residue or a peptide residue with at least one of R1, R′1, R″1 being different from hydrogen. 
         b) R2 and R3 represent, independently from each other, a hydrogen atom or represent
 a linear or branched C1-C24 alkyl moiety, optionally interrupted by a heteroatom, 
 a C4-C10 cycloalkyl moiety, 
 a linear or branched C1-C22 polyfluoroalkyl or perfluoroalkyl moiety, 
 an aryl moiety optionally substituted by one or more halogen atoms, or one or more linear or branched C1-C4 alkyl moieties, 
 an aralkyl moiety, 
 or R2 and R3 could form with the nitrogen atom a saturated ring with from 5 or 6 atoms optionally substituted by one or more linear or branched C1-C4 alkyl moieties, said saturated ring optionally containing a heteroatom, with at least one of the residues R2 or R3 being different from hydrogen, 
 
         with the proviso that the N(R2) (R3) group does not represent an amino acid or a peptide residue. 
       
     
     
         2 . The KPV tripeptide diamide derivative according to  claim 1 , wherein the salt is selected amongst hydrochlorides, hydrobromides, sulphates, acetates, citrates, tartrates, lactates, phosphates, hydrogenophosphates, propionates and succinates. 
     
     
         3 . The KPV tripeptide diamide derivate according to  claim 1  or  2 , wherein the Lysine, Proline or Valine amino acid residues are any of the stereoisomers of each of such residues. 
     
     
         4 . The KPV tripeptide diamide derivative according to  claim 1 , wherein when R1, R′1 and R″1 represent a linear or branched C1-C22 alkyl moiety interrupted by a heteroatom, said heteroatom is O, N, S or Si. 
     
     
         5 . The KPV tripeptide diamide derivative according to  claim 1 , wherein when R1, R′1 and R″1 represent an aryl moiety optionally substituted by one or more halogen atoms, such halogen is Cl, F, Br or I. 
     
     
         6 . The KPV tripeptide diamide derivative according to  claim 1 , wherein when R1 and R′1 form with C(R″1) a saturated ring containing a hetereoatom, said heteroatom is O, S or N. 
     
     
         7 . The KPV tripeptide diamide derivative according to  claim 1 , wherein when R2 and R3 represent a linear or branched C1-C22 alkyl moiety interrupted by a heteroatom, said heteroatom is O, N, S or Si. 
     
     
         8 . The KPV tripeptide diamide derivative according to  claim 1 , wherein when R2 and R3 represent an aryl moiety optionally substituted by one or more halogen atoms, such halogen is Cl, F, Br or I. 
     
     
         9 . The KPV tripeptide diamide derivative according to  claim 1 , wherein when R2 and R3 form with a nitrogen atom a saturated ring containing a heteroatom, said heteroatom is O, S or N. 
     
     
         10 . A composition comprising: a KPV tripeptide diamide derivative or salt thereof according to  claim 1  or  2  in a physiologically acceptable medium. 
     
     
         11 . The composition according to  claim 10 , wherein the physiologically acceptable medium is a cosmetic medium and the KPV tripeptide diamide derivate or salt thereof is present in an amount ranging from 10−8 to 10−3 g/100 g. 
     
     
         12 . The composition according to  claim 10 , wherein the physiologically acceptable medium is a pharmaceutical medium and the KPV tripeptide diamide derivate is present in an amount greater than 5.10−4 g/100 g.