Galactopyranosyl derivatives useful as medicaments

Patent metadata

Field	Value
Publication number	US-9321796-B2
Application number	US-201314411413-A
Country	US
Kind code	B2
Filing date	Jun 20, 2013
Priority date	Jun 28, 2012
Publication date	Apr 26, 2016
Grant date	Apr 26, 2016

Abstract

This invention relates to carbamate-containing or thiocarbamate-containing galacto-pyranosyl compounds useful as therapeutic agents and being represented by the structural formula (II), wherein: X is O or S, R is selected from the group consisting of C 1-8 alkyl, C 3-10 cycloalkyl, aryl-C 1-4 alkyl, heterocyclyl-C 1-4 alkyl, cycloalkyl-C 1-4 alkyl, aryl and heterocyclyl, wherein R is optionally substituted with one or more R 9 ; R 2 , R 3 , R 4 , R 6 and R 7 are independently selected from the group consisting of hydroxyl and protected hydroxyl groups; R 5 is selected from the group consisting C 6-30 alkyl and arylalkyl; R 8 is C 6-30 alkyl; and each R 9 is independently selected from the group consisting of halogen, hydroxy, trifluoromethyl, trifluoromethoxy, C 1-8 alkoxy, C 1-6 alkyl, cyano, methylthio, phenyl, phenoxy, chloromethyl, dichloromethyl, chloro-difluoromethyl, acetyl, nitro, benzyl, heterocyclyl and di-C 1-4 alkyl-amino, or a pharmaceutically acceptable salt thereof.

First claim

The invention claimed is:

1. A carbamate-containing galactopyranosyl compound represented by the structural formula (I):

wherein R is selected from the group consisting of C 1-8 alkyl, C 3-10 cycloalkyl, aryl-C 1-4 alkyl, heterocyclyl-C 1-4 alkyl, cycloalkyl-C 1-4 alkyl, aryl and heterocyclyl; and wherein each of the (CH 2 ) 24 CH 3 and (CH 2 ) 13 CH 3 groups may independently be replaced with a C 6-30 alkyl group, and wherein each hydroxyl group on the pyranosyl ring or the lipid chain may independently be replaced with a hydroxyl-protecting group; or a corresponding thiocarbamate-containing galactopyranosyl compound wherein a thiocarbamate group C(═S)NHR replaces the carbamate group C(═O)NHR shown in structural formula (I), or a pharmaceutically acceptable salt thereof.

2. A carbamate-containing galactopyranosyl compound according to claim 1 , wherein R is selected from the group consisting of 4-chlorophenyl, naphth-1-yl, and 4-pyridyl.

3. A carbamate-containing galactopyranosyl compound according to claim 1 , wherein R is not 4-chlorophenyl, naphth-1-yl or 4-pyridyl.

4. A carbamate-containing or thiocarbamate-containing galacto-pyranosyl compound represented by the structural formula (II):

wherein:
X is O or S,
R is selected from the group consisting of selected from the group consisting of C 1-8 alkyl, C 3-10 cycloalkyl, aryl-C 1-4 alkyl, heterocyclyl-C 1-4 alkyl, cycloalkyl-C 1-4 alkyl, aryl and heterocyclyl, wherein R is optionally substituted with one or more R 9 ;
R 2 , R 3 , R 4 , R 6 and R 7 are independently selected from the group consisting of hydroxyl and protected hydroxyl groups;
R 5 is selected from the group consisting C 6-30 alkyl and arylalkyl;
R 8 is C 6-30 alkyl; and
each R 9 is independently selected from the group consisting of halogen, hydroxy, trifluoromethyl, trifluoromethoxy, C 1-8 alkoxy, C 1-6 alkyl, cyano, methylthio, phenyl, phenoxy, chloromethyl, dichloromethyl, chloro-difluoromethyl, acetyl, nitro, benzyl, heterocyclyl and di-C 1-4 alkyl-amino, or a pharmaceutically acceptable salt thereof.

5. A carbamate-containing or thiocarbamate-containing galactopyranosyl compound according to claim 4 , wherein R 2 , R 3 , R 4 , R 6 and R 7 are benzyloxy.

6. A carbamate-containing or thiocarbamate-containing galactopyranosyl compound according to claim 4 , wherein R is phenyl substituted with one, two or three R 9 .

7. A carbamate-containing or thiocarbamate-containing galactopyranosyl compound according to claim 6 , wherein one R 9 is a para-substituent, a meta-substituent or an ortho-substituent.

8. A carbamate-containing or thiocarbamate-containing galactopyranosyl compound according to claim 4 , wherein R is selected from the group consisting of pyrid-4-yl, pyrid-3-yl, pyrid-2-yl, pyrazinyl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl and pyrimidin-6-yl, naphth-1-yl and naphth-2-yl.

9. A pharmaceutical composition comprising a therapeutically effective amount of a galactopyranosyl compound according to claim 1 , and one or more pharmaceutically acceptable excipients.

10. A pharmaceutical composition comprising a therapeutically effective amount of a galactopyranosyl compound according to claim 4 , and one or more pharmaceutically acceptable excipients.

11. A method of treatment of a disorder in a mammal, the said method comprising administering an effective amount of a galactopyranosyl compound according to claim 1 to the mammal in need thereof, said disorder being selected from the group consisting of cell proliferative disorders, immune disorders, auto-immune disorders, and infectious diseases.

12. A method of treatment of a disorder in a mammal, the said method comprising administering an effective amount of a galactopyranosyl compound according to claim 4 to the mammal in need thereof, said disorder being selected from the group consisting of cell proliferative disorders, immune disorders, auto-immune disorders, and infectious diseases.

13. An immune adjuvant to improve the efficiency of a vaccine against a human tumor or an infectious disease, comprising a galactopyranosyl compound according to claim 1 .

14. An immune adjuvant to improve the efficiency of a vaccine against a human tumor or an infectious disease, comprising a galactopyranosyl compound according to claim 4 .

Assignees

• Univ Gent

Inventors

• Elewaut Dirk
• Pauwels Nora
• Aspeslagh Sandrine
• Van Calenbergh Serge

Classifications

• A61P37/04

  Immunostimulants · CPC title

• C07H15/26 Primary

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• C07H15/04 Primary

  attached to an oxygen atom of the saccharide radical · CPC title

• C07H15/18

  Acyclic radicals, substituted by carbocyclic rings · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title