US 2016/0237178 A1 · DERIVATIVES OF N-DESULFATED GLUCOSAMINOGLYCANS AND USE AS DRUGS

Abstract

The invention relates to N-desulfated and optionally 2-O-desulfated glucosaminoglycan derivatives, wherein at least part of the adjacent diols and OH/NH2 have been converted into the corresponding aldehyde, which aldehydes have been then reduced to the corresponding alcohol. These products are endowed with heparanase inhibitory activity and anti-tumor activity. Said glucosaminoglycan derivatives are obtained from natural or synthetic glucosaminoglycan, preferably from unfractionated heparin, low molecular weight heparins (LMWHs), heparan sulfate or derivatives thereof. The invention further relates to the process for preparation of the same and further to their use as active ingredients of medicaments, also in combination with known established drugs or treatments. The present invention further relates to a process for breaking the C2-C3 linkage of glucosamine residues of a glucosaminoglycan by oxidation of said glucosaminoglycan.

Claims10

Dependent claims

A process for the preparation of a glucosaminoglycan derivative inhibiting heparanase, comprising:

a) N-desulfation of from 25% to 100% of the N-sulfated residues of a glucosaminoglycan;
b) oxidation, preferably by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N—, 3-O-non-sulfated glucosamine residues and of the 2-O-non-sulfated uronic acid residues of said glucosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NH2 to aldehydes;
c) reduction, preferably by sodium borohydride, of said oxidized glucosaminoglycan, under conditions effective to convert said aldehydes to alcohols.

Dependencies are inferred from the claim text.

Derivatives of n-desulfated glucosaminoglycans and use as drugs

Life of this patent

Derivatives of n-desulfated glucosaminoglycans and use as drugs

Life of this patent

Abstract

Claims10