Glycolipids and pharmaceutical compositions thereof for use in therapy

Patent metadata

Field	Value
Publication number	US-2017275323-A1
Application number	US-201515301264-A
Country	US
Kind code	A1
Filing date	Apr 7, 2015
Priority date	Apr 4, 2014
Publication date	Sep 28, 2017
Grant date	—

Abstract

A compound of Formula I: R1-L1-C(A)(A′)-CH 2 , -L2-R2 or a pharmaceutically acceptable salt thereof, for use in medicine, for example in the treatment of a disease or condition selected from the group comprising cancer, autistic spectrum disorders. Alzheimer's disease, Parkinson's disease, Huntingdon's disease, muscle wasting and viral infection, wherein: R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; A is selected from hydrogen and a C1-C6 alkyl group: A′ is selected from hydrogen, a C3-C6 alkyl group, and L3-R3; wherein L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; and wherein if A′ is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group; and wherein if A′ is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.

First claim

1 . A compound of Formula I:
R1-L1-C(A)(A′)-CH 2 -L2-R2  (I)
or a pharmaceutically acceptable salt thereof, for use in medicine, wherein:
R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group;
L1 is a linking group;
L2 is a linking group;
R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group;
A is selected from hydrogen and a C1-C6 alkyl group;
A′ is selected from hydrogen, a C1-C6 alkyl group, and L3-R3;
wherein
L3 is a linking group; and
R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group;
and wherein if A′ is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group
and wherein if A′ is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.

2 . The compound of claim 1 , wherein R1 is a carbohydrate group or derivative thereof.

3 . The compound of claim 1 , wherein 1, 2, 3, 4, 5, 6, 7, 9 or more C═C double bond is contained within the —C(A)(A′)-CH 2 -L2-R2 part of the compound.

4 . (canceled)

5 . The compound of claim 3 , wherein the or each C═C double bond is located five or more atoms in the chain away from the L1 group.

6 . The compound of claim 3 , wherein within the —C(A)(A′)-CH 2 -L2-R2 part of the compound there is 1, 2 or more C═C double bond that is located more than 6 or 8 atoms, but less than 17 atoms in the chain away from the L1 group.

7 .- 8 . (canceled)

9 . The compound of claim 3 , wherein A′ is L3-R3, and one or both of R2 and R3 is a group that contains one, two, or more C═C double bonds.

10 . (canceled)

11 . The compound of claim 9 wherein:
(a) R2 and/or R3 is a C10-C24 derivative of an alkyl group, where the alkyl group is substituted with one or more substituent groups and wherein said one or more substituent groups between them comprise one or more C═C double bond; or
(b) R2 and/or R3 is a C10-C24 alkenyl group; or
(c) R2 and/or R3 is a C10-C24 derivative of an alkenyl group, wherein the alkenyl group is substituted with one or more substituent groups wherein said one or more substituent groups between them comprise one or more C═C double bond.

12 . The compound of claim 9 , wherein R2 and R3 each contain one, two, or more C═C double bond.

13 . (canceled)

14 . The compound of claim 1 , wherein A′ is L3-R3, and both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.

15 . The compound of claim 1 , wherein the compound of Formula I is of Formula Ia

or a pharmaceutically acceptable salt thereof,
wherein:
R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group;
L1 is a linking group;
L2 is a linking group;
R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group;
L3 is a linking group; and
R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group;

and wherein one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.

16 . The compound of claim 15 , wherein:
R1 is a carbohydrate group or derivative thereof, L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a derivative thereof, a C2-C24 alkenyl or a derivative thereof and a C2-C24 alkynyl group or a derivative thereof, L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a derivative thereof, a C2-C24 alkenyl or a derivative thereof and a C2-C24 alkynyl group or a derivative thereof,
and one or both of R2 and R3 are a C10-C24 alkyl, alkenyl or alkynyl group or a derivative thereof.

17 . The compound for use of claim 16 , wherein:
R1 is a carbohydrate group or derivative thereof, L1 is a linking group; L2 is a linking group; R2 is a C10-C24 alkyl, alkenyl or alkynyl group or a derivative thereof; L3 is a linking group; and R3 is a C10-C24 alkyl, alkenyl or alkynyl group or a derivative thereof.

18 . The compound of claim 1 ,
wherein the R1 group has from 6-18 carbon atoms; the R1 group is a cyclic monosaccharide or derivative thereof; and/or the R1 group is a galactoside or a glucoside or a mannoside, or a derivative thereof; wherein each of the L1 linking group, the L2 linking group and the L3 linking group independently have from 1-12 carbon atoms; and/or each of the L1 linking group, the L2 linking group and the L3 linking group are independently selected from alkylene groups, cycloalkyene groups, alkenylene groups, ether groups, imino groups, carbonyl groups, including ester groups and amido groups and phosphate groups, (hetero)arylene groups, amino groups, thioether groups, and divalent residues containing any of combinations of these divalent groups bonded to each other in series

19 .- 22 . (canceled)

23 . The compound of claim 18 , wherein the L1 linking group is a C1-C8 alkylene linking group or a glycoside linker;
wherein the L2 linking group is a C1-C4 alkylene linking group or C1-C4 ester group or C1-C4 amido group; and/or wherein the L3 linking group is a C1-C4 alkylene linking group or C1-C4 ester group or C1-C4 amido group.

24 .- 25 . (canceled)

26 . The compound of claim 23 , wherein the L3 linking group is CH 2 -L2; wherein the R2 group is a C12-C24 alkenyl group; wherein the R3 group is a C12-C24 alkenyl group.

27 .- 28 . (canceled)

29 . The compound of claim 1 , wherein the compound has a Formula:

wherein the groups R1, R2, R3 are in accordance with any of the definitions of the preceding claims, and X is either absent or is —O—, —NR a —, —S— or —CR a R b —, wherein R a and R b are independently selected from the group consisting of hydrogen and C1-C4 alkyl, and n is an integer of from 1 to 6, e.g. 1, 2 or 3.

30 . The compound of claim 1 , wherein the

Assignees

• Univ Nottingham

Inventors

• Bottley Andrew
• Hayes Christopher
• Seymour Graham
• Grabowska Anna
• Clarke Philip

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title