Lipid-linked prodrugs

Patent metadata

Field	Value
Publication number	US-10780174-B2
Application number	US-201616063666-A
Country	US
Kind code	B2
Filing date	Dec 22, 2016
Priority date	Dec 23, 2015
Publication date	Sep 22, 2020
Grant date	Sep 22, 2020

Abstract

This invention provides lipid-linked prodrugs having structures as set out herein. Uses of such lipid-linked prodrug compounds for treatment of various indications, and methods for making and using lipid-linked prodrugs are also provided.

First claim

What is claimed is:

1. A compound, the compound having the structure of Formula III:

wherein:
A-Z is dexamethasone, wherein Z is an electronegative atom selected from N or O, such that the dexamethasone is represented by the formula A-Z—H when Z has lost an H to covalently bind to Y;
Y is CH 2 or C(═O);
T5 is 0-6 carbon atoms; and
L4 is C 9 -C 29 linear or branched carbon chain, having one or more, cis or trans C═C double bonds and optionally substituted with OH or has the Formula V:

wherein,
T2 is 1-4 carbon atoms;
T3 is 0-4 carbon atoms;
T4 is 0-4 carbon atoms;
J1 is —O—C(═O)-L1;
J2 is —COOH, —OH, —NH 2 , —SH, —NMe 2 , or —NHMe; and
L1 is C 9 -C 29 linear or branched carbon chain, optionally having one or more, cis or trans C═C double bonds and optionally substituted with OH.

2. The compound of claim 1 , wherein the compound has the structure of Formula II:

wherein:
Y is CH 2 or C(═O);
T1 is 0-4 carbon atoms;
T2 is 1-3 carbon atoms; and
J2 is —COOH, —OH, —NH 2 , —NMe 2 , or —NHMe.

3. The compound of claim 1 , wherein the compound has the structure of Formula III:

wherein:
Y is CH 2 or C(═O); and
T5 is 0-4 carbon atoms.

4. The compound of claim 1 , wherein
L4 is C 9 -C 29 linear or branched carbon chain, having one or more, cis or trans C═C double bonds.

5. The compound of any one of claim 1 , wherein Y is CH 2 or C(═O); and T5 are 0-2 carbon atoms.

6. A pharmaceutical composition, the pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

7. A method for suppressing immunity, the method comprising administering a compound of claim 1 to a subject in need thereof.

8. The compound of claim 1 , wherein the compound is selected from one or more of the following:

9. The method of claim 7 , wherein the compound is selected from one or more of the following:

10. A method for suppressing immunity, the method comprising administering a compound of claim 2 to a subject in need thereof.

11. A method for suppressing immunity, the method comprising administering a compound of claim 3 to a subject in need thereof.

12. A method for suppressing immunity, the method comprising administering a compound of claim 4 to a subject in need thereof.

13. A pharmaceutical composition, the pharmaceutical composition comprising a compound of claim 8 and a pharmaceutically acceptable carrier.

14. A pharmaceutical composition, the pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.

15. A pharmaceutical composition, the pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier.

16. A pharmaceutical composition, the pharmaceutical composition comprising a compound of claim 4 and a pharmaceutically acceptable carrier.

Assignees

• Univ British Columbia

Inventors

• Ciufolini Marco A
• Cullis Pieter R
• Tam Yuen Yi
• Zaifman Joshua

Classifications

• C07J5/0038 Primary

  by an alkyl group · CPC title

• C07J41/005

  the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives · CPC title

• C07J5/0076

  by an alkyl group · CPC title

• C07J31/006

  not covered by C07J31/003 · CPC title

• C07D475/08

  with a nitrogen atom directly attached in position 2 · CPC title