AZA-pyridone compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-9328119-B2
Application number	US-201414482886-A
Country	US
Kind code	B2
Filing date	Sep 10, 2014
Priority date	Sep 12, 2013
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

Disclosed herein are aza-pyridone compounds, pharmaceutical compositions that include one or more aza-pyridone compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an orthomyxovirus infection, with an aza-pyridone compounds. Examples of an orthomyxovirus viral infection include an influenza infection.

First claim

What is claimed is:

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the structure:

wherein:
is a single bond or double bond;
R 1 is selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl, —C(═O)Y 1 , —C(═O)—O—Y 1 , —(CH 2 )—O—(C═O)—Y 1 , —(CH 2 )—O—(C═O)—O—Y 1 , —(CHCH 3 )—O—(C═O)—Y 1 and —(CHCH 3 )—O—(C═O)—O—Y 1 ;
R 2 is selected from the group consisting of hydrogen, an optionally substituted C 1-6 alkyl, an optionally substituted heterocyclyl, an optionally substituted cycloalkyl(C 1-6 alkyl), an optionally substituted aryl(C 1-6 alkyl), an optionally substituted heteroaryl(C 1-6 alkyl) and an optionally substituted heterocyclyl(C 1-6 alkyl);
R 3a and R 3b are independently hydrogen or an optionally substituted C 1-4 alkyl;
R 4 and R 5 are independently selected from the group consisting of hydrogen, an optionally substituted aryl, an optionally substituted aryl(C 1-6 alkyl) an optionally substituted heteroaryl and an optionally substituted heteroaryl(C 1-6 alkyl), provided that at least one of R 4 and R 5 is not hydrogen; or
R 4 and R 5 are taken together to form an optionally substituted tricyclic cycloalkenyl or an optionally substituted tricyclic heterocyclyl;
R 6 is selected from the group consisting of hydrogen, halogen, —CN, an optionally substituted C 1-6 alkyl, an optionally substituted aryl, an optionally substituted heteroaryl, —CH 2 OH, —CH(Y 2 )(OH) and —C(O)Y 2 ;
Y 1 and Y 2 are independently selected from the group consisting of an optionally substituted C 1-6 alkyl, an optionally substituted C 3-6 cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, a mono-substituted amino group, a di-substituted amino and —C(R 7 )NHR 8 ; and
R 7 and R 8 are independently hydrogen or an optionally substituted C 1-4 alkyl.

2. The compound of claim 1 , wherein R 4 is an optionally substituted aryl.

3. The compound of claim 2 , wherein the optionally substituted aryl is an optionally substituted phenyl.

4. The compound of claim 1 , wherein R 4 is an optionally substituted heteroaryl.

5. The compound of claim 1 , wherein R 5 is an optionally substituted aryl.

6. The compound of claim 5 , wherein the optionally substituted aryl is an optionally substituted phenyl.

7. The compound of claim 1 , wherein R 5 is an optionally substituted heteroaryl.

8. The compound of claim 1 , wherein R 4 and R 5 are taken together to form an optionally substituted tricyclic heterocyclyl.

9. The compound of claim 8 , wherein the optionally substituted tricyclic heterocyclyl is an optionally substituted moiety selected from the group consisting of:

10. The compound of claim 1 , wherein R 2 is hydrogen.

11. The compound of claim 1 , wherein R 2 is an optionally substituted C 1-6 alkyl.

12. The compound of claim 11 , wherein R 2 is an unsubstituted C 1-6 alkyl.

13. The compound of claim 1 , wherein R 2 is an optionally substituted aryl(C 1-6 alkyl).

14. The compound of claim 1 , wherein R 1 is hydrogen.

15. The compound of claim 1 , wherein R 1 is an unsubstituted C 1-4 alkyl.

16. The compound of claim 1 , wherein R 1 is —C(═O)Y 1 , —C(═O)—O—Y 1 , —(CH 2 )—O—(C═O)—Y 1 , —(CH 2 )—O—(C═O)—O—Y 1 , —(CHCH 3 )—O—(C═O)—Y 1 or —(CHCH 3 )—O—(C═O)—O—Y 1 .

17. The compound of claim 16 , R 1 is —C(═O)Y 1 .

18. The compound of claim 16 , R 1 is —C(═O)—O—Y 1 .

19. The compound of claim 1 , wherein R 6 is hydrogen.

20. The compound of claim 1 , wherein R 3a is hydrogen; and R 3b is hydrogen.

21. The compound of claim 1 , wherein is a single bond.

22. The compound of claim 1 , wherein is a double bond.

23. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt of the foregoing.

24. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt of the foregoing.

25. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt of the foregoing.

26. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.

27. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

28. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

29. The compound of claim 1 , wherein the compound is

Assignees

• Alios Biopharma Inc

Inventors

• Hendricks Robert Than
• Beigelman Leonid
• Smith David Bernard
• Stoycheva Antitsa Dimitrova

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/215

  of carboxylic acids · CPC title

• A61K31/4965

  Non-condensed pyrazines · CPC title