Compounds useful in HIV therapy

Patent metadata

Field	Value
Publication number	US-11274102-B2
Application number	US-201816758085-A
Country	US
Kind code	B2
Filing date	Oct 24, 2018
Priority date	Oct 30, 2017
Publication date	Mar 15, 2022
Grant date	Mar 15, 2022

Abstract

The invention relates to compounds of Formula (I), (II) or (III), salts thereof, pharmaceutical compositions thereof, as well as therapeutic methods of treatment and prevention.

First claim

What is claimed is:

1. A compound of the formula (I):

wherein:
Y 1 is a 5- or 6-membered aryl or heteroaryl optionally substituted by one or more substituents independently selected from the group consisting of chloro, fluoro, oxo, and alkoxy;
R 1 is C 1 -C 6 alkylene; and
Y 2 is a ring of the formula:

wherein R 2 is selected from the group consisting of -chloro, fluoro, oxo and alkoxy;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein Y 1 is an aryl.

3. The compound according to claim 2 , wherein Y 1 is an aryl substituted by Cl.

4. The compound according to claim 3 , wherein Y 1 is of the formula:

5. The compound according to claim 1 , wherein Y1 is a 5-membered heteroaryl.

6. The compound according to claim 5 , wherein the 5-membered heteroaryl contains at least one heteroatom which is O or S.

7. The compound according to claim 1 , wherein R 1 is C 1 alkyl.

8. The compound according to claim 1 , wherein R 1 is C 2 alkyl.

9. The compound according to claim 1 , selected from the group consisting of:

Parent Structure
Chemical Name

1-((5-((5-(4-chlorophenyl)furo[2,3- d]pyrimidin-4-yl)thio)-1,3,4-oxadiazol- 2-yl)methyl)pyrrolidin-2-one

1-((5-((5-(4-chlorophenyl)furo[2,3- d]pyrimidin-4-yl)thio)-1,3,4-oxadiazol- 2-yl)methyl)pyrrolidin-2-one

1-((5-((5-(4-chlorophenyl) furo[2,3-d]pyrimidin-4-yl)thio)- 1,3,4-oxadiazol-2-yl) methyl)pyrrolidin-2-one

1-((5-((5-(furan-2-yl)furo[2,3- d]pyrimidin-4-yl)thio)-1,3,4-oxadiazol- 2-yl)methyl)pyrrolidin-2-one

1-((5-((5-(furan-2-yl)furo[2,3- d]pyrimidin-4-yl)thio)-1,3,4-oxadiazol- 2-yl)methyl)pyrrolidin-2-one

1-((5-((5-(thiophen-2-yl)furo[2,3- d]pyrimidin-4-yl)thio)-1,3,4- oxadiazol-2-yl)methyl)pyrrolidin-2- one

1-((5-((5-(5-methylthiophen-2- yl)furo[2,3-d]pyrimidin-4-yl)thio)-1,3,4- oxadiazol-2-yl)methyl)pyrrolidin-2-one

and a pharmaceutically acceptable salt thereof.

10. A compound of the formula (II):

wherein R 1 is C 1 -C 6 alkyl; and
R 3 is hydrogen, oxo, chloro or fluoro.

11. A compound of the formula (III):

or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

13. The composition of claim 12 , wherein the compound is present in an amorphous form.

14. The composition of claim 12 , wherein the composition is in a tablet form.

15. The composition of claim 12 , wherein the compound is present as a spray dried dispersion.

16. A method of curing an HIV infection in a subject comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

17. A method of treating an HIV infection in a subject comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

18. A method of preventing an HIV infection in a subject at risk for developing an HIV infection, comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Glaxosmithkline Ip Dev Ltd

Inventors

• Favre David
• Ferris Robert G
• Tang Jun

Classifications

• A61K9/16

  Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)} · CPC title

• C07D491/048 Primary

  the oxygen-containing ring being five-membered · CPC title

• A61K9/20

  Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} · CPC title