Substituted anionic compounds consisting of a backbone made up of a discrete number of saccharide units

Abstract

The invention relates to substituted anionic compounds consisting of a backbone made up of a discrete number u of between 1 and 8 (1≦u≦8) of identical or different saccharide units, linked via identical or different glycosidic bonds, said saccharide units being chosen from the group consisting of hexoses in cyclic form or in open reduced form, which are randomly substituted. It also relates to the process for the preparation thereof and to the pharmaceutical compositions comprising same.

What is claimed is: 
     
         1 . Substituted anionic compounds, in isolated form or as a mixture, consisting of a backbone made up of a discrete number u of between 1 and 8 (1≦u≦8) of identical or different saccharide units, linked via identical or different glycosidic bonds, said saccharide units being chosen from the group consisting of hexoses in cyclic form or in open reduced form, characterized in that they are substituted with:
 c) at least one substituent of general formula V:
   —[R 1 ] a -[AA] m    formula V
 
 
 the substituents being identical or different when there are at least two substituents, in which: 
 the radical -[AA]- denotes an amino acid residue, 
 the radical —R 1 — being:
 either a bond and then a=0, and the amino acid residue -[AA] is directly bonded to the backbone via a function G a , 
 or a C 2  or C 15  carbon-based chain, and then a=1, which is optionally substituted and/or comprising at least one heteroatom chosen from O, N and S and at least one acid function before the reaction with the amino acid, said chain forming, with the amino acid residue -[AA], an amide function, and is attached to the backbone by means of a function F a  resulting from a reaction between a hydroxyl function borne by the backbone and a function or a substituent borne by the precursor of the radical —R 1 —, 
 
 F a  is a function chosen from ether, ester or carbamate functions, 
 G a  is a carbamate function, 
 m is equal to 1 or 2, 
 the degree of substitution of the saccharide units, j, with —[R 1 ] a -[AA] m  being strictly greater than 0 and less than or equal to 6, 0<j≦6; 
 d) and, optionally, one or more substituents —R′ 1 , 
 the substituent —R′ 1  being a C 2  to C 15  carbon-based chain which is optionally substituted and/or comprising at least one heteroatom chosen from O, N and S and at least one acid function in the form of an alkali metal cation salt, said chain being bonded to the backbone via a function F′ a  resulting from a reaction between a hydroxyl function or a carboxylic acid function borne by the backbone and a function or a substituent borne by the precursor of the substituent —R′ 1 , 
 F′ a  is an ether, ester or carbamate function, 
 the degree of substitution of the saccharide units, i, with —R′ 1 , being between 0 and 6-j, 0≦i≦6-j and, 
 F a  and F a ′ are identical or different, 
 F a  and G a  are identical or different, 
 i+j≦6, 
 —R′ 1  identical to or different than —R 1 —, 
 the free salifiable acid functions borne by the substituent —R′ 1  are in the form of alkali metal cation salts, 
 said identical or different glycosidic bonds being chosen from the group consisting of glycosidic bonds of (1,1), (1,2), (1,3), (1,4) or (1,6) type, in an alpha or beta geometry. 
 
     
     
         2 . The anionic compounds as claimed in  claim 1 , wherein the radical —R 1  is chosen from the following groups, in which*represents the site of attachment to F a : 
       
         
           
           
               
               
           
         
       
       or their salts of alkali metal cations chosen from the group consisting of Na +  or K + . 
     
     
         3 . The anionic compounds as claimed in  claim 1 , wherein the radical —R 1 — before attachment to the radical [AA] is —CH 2 —COOH. 
     
     
         4 . The anionic compounds as claimed in  claim 1 , wherein the radical —R′ 1  is chosen from the following groups, in which*represents the site of attachment to F′ a : 
       
         
           
           
               
               
           
         
       
       or their salts of alkali metal cations chosen from the group consisting of Na +  or K + . 
     
     
         5 . The anionic compounds as claimed in  claim 1 , wherein the radical —R′ 1  is a radical —CH 2 COOH. 
     
     
         6 . The anionic compounds as claimed in  claim 1 , wherein the amino acids are chosen from alpha-amino acids. 
     
     
         7 . The anionic compounds as claimed in  claim 6 , wherein the alpha-amino acids are chosen from natural alpha-amino acids. 
     
     
         8 . The anionic compounds as claimed in  claim 7 , wherein the natural alpha-amino acids are chosen from hydrophobic amino acids chosen from the group comprising tryptophan, leucine, alanine, isoleucine, glycine, phenylalanine, tyrosine and valine, in their L, D or racemic forms. 
     
     
         9 . The anionic compounds as claimed in  claim 7 , wherein the natural alpha-amino acids are chosen from polar amino acids chosen from the group comprising aspartic acid, glutamic acid, lysine and serine, in their L, D or racemic forms. 
     
     
         10 . The anionic compounds as claimed in  claim 6 , wherein the alpha-amino acid is chosen from the group consisting of alpha-methylphenylalanine, alpha-methyltyrosine, O-methyltyrosine, alpha-phenylglycine, 4-hydroxyphenylglycine and 3,5-dihydroxyphenylglycine, in their L, D or racemic forms. 
     
     
         11 . The anionic compounds as claimed in  claim 1 , wherein at least one saccharide unit is in cyclic form. 
     
     
         12 . The anionic compounds as claimed in  claim 1 , wherein at least one saccharide unit is in open reduced form. 
     
     
         13 . The anionic compounds as claimed in  claim 1 , wherein the backbone is made up of a discrete number of between 3 and 5 saccharide units. 
     
     
         14 . The anionic compounds as claimed in  claim 1 , wherein the backbone is made up of a discrete number u=3 saccharide units. 
     
     
         15 . The anionic compounds as claimed in  claim 1 , wherein the backbones are obtained by enzymatic degradation of a polysaccharide followed by purification. 
     
     
         16 . The anionic compounds as claimed in  claim 1 , wherein the backbones are obtained by chemical degradation of a polysaccharide followed by purification. 
     
     
         17 . The anionic compounds as claimed in  claim 1 , wherein the backbones are obtained chemically, by covalent coupling of lower-molecular-weight precursors. 
     
     
         18 . A pharmaceutical composition which comprises an anionic compound as claimed in  claim 1  and an active ingredient chosen from the group consisting of proteins, glycoproteins, peptides and nonpeptide therapeutic molecules.