FGF receptor-activating N-sulfate oligosaccharides, preparation thereof, and therapeutic use thereof

Patent metadata

Field	Value
Publication number	US-9527930-B2
Application number	US-201213369677-A
Country	US
Kind code	B2
Filing date	Feb 9, 2012
Priority date	Aug 14, 2009
Publication date	Dec 27, 2016
Grant date	Dec 27, 2016

Abstract

The invention relates to FGF receptor-activating N-sulfate oligosaccharides having Formula (I), wherein R 1 , R 4 , R 6 , and R 8 are —OSO 3 − or hydroxyl groups, R 2 is an —O-alkyl group or a monosaccharide having Formula (II), R 3 is a disaccharide having Formula (III), R 5 is a disaccharide having Formula (IV), R 7 is a hydroxyl group or a disaccharide having Formula (VI), and R 9 is a hydroxyl or —O-alkyl group or a disaccharide having Formula (VII), where R 10 — is an —O-alkyl group. The invention further relates to the preparation of said oligosaccharides and to the therapeutic use thereof.

First claim

What is claimed is:

1. An oligosaccharide compound of formula (I):

in which
R 1 represents a group —OSO 3 − or a hydroxyl group;
R 2 represents a monosaccharide of formula (II), in which R represents an alkyl group,

R 3 represents a disaccharide of formula (III):

in which
R 4 represents a group —OSO 3 − or a hydroxyl group;
R 5 represents a disaccharide of formula (IV):

in which
R 6 represents a group —OSO 3 − or a hydroxyl group; and
R 7 represents a hydroxyl group;

in acid form or in the form of a pharmaceutically acceptable salt thereof.

2. An oligosaccharide compound of formula (I):

in which
R 1 represents a group —OSO 3 − or a hydroxyl group;
R 2 represents a group —O-alkyl, wherein the alkyl group is selected from the group consisting of methyl, ethyl, isopropyl, butyl, isobutyl and tert-butyl;
R 3 represents a disaccharide of formula (III):

in which
R 4 represents a group —OSO 3 − or a hydroxyl group; and
R 5 represents a disaccharide of formula (IV):

in which
R 6 represents a group —OSO 3 − or a hydroxyl group; and
R 7 represents a disaccharide of formula (VI):

in which
R 8 represents a group —OSO 3 − or a hydroxyl group; and
R 9 represents a disaccharide of formula (VII);

in which R 10 represents a group —O-alkyl;
on condition that: R 9 represents a hydroxyl group or a group O-alkyl when R 2 represents a monosaccharide of formula (II) as defined above; R 7 represents a disaccharide of formula (VI) as defined above when R 2 represents a group O-alkyl; and R 1 , R 4 , R 6 and R 8 do not simultaneously represent hydroxyl groups;
in acid form or in the form of a pharmaceutically acceptable salt thereof.

3. An oligosaccharide compound of formula (I):

in which
R 1 represents a group —OSO 3 − or a hydroxyl group;
R 2 represents a group —O-alkyl, wherein the alkyl group is selected from the group consisting of methyl, ethyl, isopropyl, butyl, isobutyl and tert-butyl;
R 3 represents a disaccharide of formula (III):

in which
R 4 represents a group —OSO 3 − or a hydroxyl group; and
R 5 represents a disaccharide of formula (IV):

in which
R 6 represents a group —OSO 3 − or a hydroxyl group;
R 7 represents a disaccharide of formula (VI):

in which
R 8 represents a group —OSO 3 − or a hydroxyl group; and
R 9 represents a group —O-alkyl,

on condition that R 1 , R 4 , R 6 and R 8 do not simultaneously represent hydroxyl groups;
in acid form or in the form of a pharmaceutically acceptable salt thereof.

4. An oligosaccharide compound selected from the group consisting of:
methyl (sodium 4-O-propyl-2-O-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-(2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranosyl)-(1→4)-[(sodium 2-0-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-(2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranosyl-(1→4)] 2 -(sodium 2-O-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranoside (No. 1);
methyl (sodium 4-O-propyl-2-O-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-(2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranosyl)-(1→4)-[(sodium 2-O-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-(2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranosyl-(1→4)] 3 -(sodium 2-O-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranoside (No. 2); and
sodium [methyl (sodium 2-O-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-(2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranosyl)-(1→4)-[(sodium 2-O-sodium sulfonato-α- L -idopyranosyluronate)-(1→4)-(2-deoxy-6-O-sodium sulfonato-2-sodium (sulfonatoamino)-α- D -glucopyranosyl)-(1→4)] 2 -2-O-sodium sulfonato-α- L -idopyranoside]-uronate (No. 3).

5. A pharmaceutical composition comprising an oligosaccharide compound, in acid form or in the form of a pharmaceutically acceptable salt thereof, according to claim 1 , and at least one pharmaceutically acceptable excipient.

6. A pharmaceutical composition comprising an oligosaccharide compound, in acid form or in the form of a pharmaceutically acceptable salt thereof, according to claim 4 , and at least one pharmaceutically acceptable excipient.

7. A pharmaceutical composition comprising an oligosaccharide compound, in acid form or in the form of a pharmaceutically acceptable salt thereof, according to claim 3 , and at least one pharmaceutically acceptable excipient.

8. A pharmaceutical composition comprising an oligosaccharide compound, in acid form or in the form of a pharmaceutically acceptable salt thereof, according to claim 7 , and at least one pharmaceutically acceptable excipient.

Assignees

• Duchaussoy Philippe
• Fons Pierre
• Froidbise Alexandre
• Sanofi Sa

Inventors

• Duchaussoy Philippe
• Fons Pierre
• Froidbise Alexandre

Classifications

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title