Carboxylated derivatives of glycosaminoglycans and use as drugs

Abstract

The invention relates to glycosaminoglycan derivatives, endowed with heparanase inhibitory activity and antitumor activity, bearing carboxylate groups in positions 2 and 3 of at least part of the glycosaminoglycan residues, and to the process for preparing the same. The glycosaminoglycan derivatives of the present invention are generated starting from natural or synthetic glycosaminoglycans, preferably heparin or low molecular weight heparin, optionally 2-O- and 2N-desulfated by two steps of oxidation. By the first oxidation, adjacent diols and optionally adjacent OH/NHof the glycosaminoglycan residues are converted to aldehydes and by the second oxidation said dialdehydes are converted to carboxylate groups. The first oxidation preferably leads to the cleavage of C-Clinkage of the ring of oxidable residues. The invention further relates to a process for the preparation of said glycosaminoglycan derivatives and further to their use as active ingredients of medicaments. Furthermore, the invention relates to pharmaceutical compositions comprising di/tricarboxylated heparin derivatives, as active agent.