Polysaccharidic esters of N-derivatives of glutamic acid

Abstract

The present invention is related to polysaccharide esters of N-derivatives of glutamic acid (N-GA derivatives). These polysaccharidic esters have antiproliferative activity and are characterized by a low systemic toxicity. The esters of the invention are used in the prevention and therapy of diseases caused by cellular hyperproliferation, particularly psoriasis, tumors, rheumatoid arthritis, or intestinal inflammatory pathologies.

1 - 33 . (Cancelled)  
     
     
         34 . A pharmaceutical composition comprising: 
 at least one suitable pharmacologically acceptable excipient and/or diluent;    as an active ingredient, a polysaccharidic ester of the compound of formula (I),                          wherein R 2  and R 4  are independent from one another, are selected from the group consisting of —NH 2 , —OH, —OCH 3 , C 1 -C 5  alkyl, and ═O, and the 6-membered ring containing the two nitrogen atoms is optionally aromatic; X and Y are selected from the group consisting of —C(R 5 )═, —CH(R 5 )—, —NH—, and —N═, and wherein R 5  represents —H or C 1 -C 5  alkyl, and the ring including X and Y is optionally aromatic; Z is selected from the group consisting of —O—, —CH(R 10 )—, and —N(R 10 )—, and wherein R 10  represents —H, C 1 -C 5  alkyl, C 1 -C 5  alkenyl, C 1 -C 5  alkynyl, or a 5-6 membered heterocyclic ring with 1-3 heteroatoms selected from the group consisting of nitrogen, sulphur and oxygen; and Ar is 1,4-phenyl, possibly condensed with one or more 5-6-membered aromatic rings, optionally heterocycles, optionally substituted with R 2  as defined above; and characterized in that only the primary hydroxy groups present on the monosaccharide units of the polysaccharide are either partially or totally esterified with the γ-carboxylic group of the compounds of formula (I); and    wherein said composition is formulated for parenteral, oral or topical administration.    
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein said parenteral administration takes place intravenously, intramuscularly, intrarticularly or subcutaneously.  
     
     
         36 . A method for the treatment of diseases characterized by cell hyperproliferation comprising administering to a patient in need thereof the pharmaceutical composition of  claim 34 .  
     
     
         37 . A method for the treatment of autoimmune or inflammatory pathologies comprising administering to a patient in need thereof the pharmaceutical composition of  claim 34 .  
     
     
         38 . A method for the treatment of dermatological diseases comprising administering to a patient in need thereof the pharmaceutical composition of  claim 34 .  
     
     
         39 . A method for the treatment of intestinal inflammatory pathologies comprising administering to a patient in need thereof the pharmaceutical composition of  claim 34.