Lipid disulfide prodrugs and uses related thereto

Patent metadata

Field	Value
Publication number	US-11090316-B2
Application number	US-202016899913-A
Country	US
Kind code	B2
Filing date	Jun 12, 2020
Priority date	Jul 13, 2017
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

This disclosure relates to lipid disulfide prodrugs and in particular to lipid disulfide phosphodiester nucleosides and derivatives thereof, pharmaceutical compositions, and uses related thereto. According to one embodiment of the disclosure there is provided a compound of Formula I,

or pharmaceutically acceptable salts or derivatives thereof, wherein substituents are disclosed herein.

First claim

The invention claimed is:

1. A method of treating a viral infection selected from the group consisting of human immunodeficiency virus (HIV) infection and hepatitis B virus (HBV) infection, comprising administering to a subject in need thereof an effective amount of a compound of Formula I,

or a salt thereof, wherein,
W is

Z is O, S, or Se;
Y is O, S, or NH;
T is an aryl or alkyl linking group;
R 1 is a saturated hydrocarbon chain having 6 or more carbon atoms;
R 2 is R 1 SST-, hydrogen, alkyl, aryl, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R 2 is optionally substituted with one or more, the same or different, R 10 ;
R 10 is deuterium, alkyl, alkenyl, alkynyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, benzyl, benzoyl, carbocyclyl, aryl, or heterocyclyl, wherein R 10 is optionally substituted with one or more, the same or different, R 11 ; and
R 11 is deuterium, halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methyl sulfinyl, ethylsulfinyl, mesyl, ethyl sulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, benzyl, benzoyl, carbocyclyl, aryl, or heterocyclyl.

2. The method of claim 1 , wherein T is a C 2 to C 6 alkyl.

3. The method of claim 1 , wherein Z and Y are each O.

4. The method of claim 1 , wherein R 1 is a C 6 to C 20 saturated hydrocarbon chain.

5. The method of claim 1 , wherein R 2 is R 1 SST-, hydrogen, alkyl, aryl or phenyl.

6. The method of claim 1 , wherein R 2 is hydrogen, methyl, or alkyl.

7. The method of claim 1 , wherein the compound is selected from the following compounds as free acids or salts thereof:

8. The method of claim 1 wherein the subject is at risk of, exhibiting symptoms of, suffering from, or diagnosed with the viral infection.

9. The method of claim 1 wherein the compound is administered in combination with another antiviral agent.

10. The method of claim 1 , wherein T is —(CH 2 ) n —, wherein n is 2, 3, 4, 5, or 6.

11. The method of claim 10 , wherein n is 2.

12. The method of claim 10 , wherein n is 4 or 5.

13. The method of claim 1 , wherein T is —C 6 H 4 —, —CH 2 —C 6 H 4 —, —C 6 H 4 —CH 2 —, or —CH 2 —C 6 H 4 —CH 2 —.

14. The method of claim 1 , wherein the viral infection is HIV infection.

15. The method of claim 1 , wherein the viral infection is HBV infection.

Assignees

• Univ Emory

Inventors

• Liotta Dennis
• Giesler Kyle

Classifications

• A61K47/543

  Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K31/52

  Purines, e.g. adenine · CPC title