Bicyclic compounds

Patent metadata

Field	Value
Publication number	US-11957683-B2
Application number	US-202217807057-A
Country	US
Kind code	B2
Filing date	Jun 15, 2022
Priority date	Jun 18, 2021
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

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

wherein:
n is 0 or 1;
Z 1 is —C(═O)—or —NH—C(═O)—;
R 1 is selected from the group consisting of an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted aryl(C 1-4 alkyl), an optionally substituted heteroaryl(C 1-4 alkyl) and an optionally substituted heterocyclyl(C 1-4 alkyl);
R 2 and R 3 are independently selected from the group consisting of hydrogen, an optionally substituted C 1-4 alkyl, an optionally substituted C 2-4 alkenyl, an optionally substituted C 2-4 alkynyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted aryl(C 1-4 alkyl), an optionally substituted heteroaryl(C 1-4 alkyl) and an optionally substituted heterocyclyl(C 1-4 alkyl);
R 4 and R 5 are independently selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted aryl(C 1-4 alkyl), an optionally substituted heteroaryl(C 1-4 alkyl) and an optionally substituted heterocyclyl(C 1-4 alkyl);
R 6 and R 7 are independently selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl and an unsubstituted C 1-4 haloalkyl;
R 8 is —NR 10A R 10B or an optionally substituted C 2-12 alkynyl, wherein the C 2-12 alkynyl is optionally substituted with one or more substituents selected from the group consisting of amino, —NH—C(═O)(an unsubstituted C 1-4 alkyl), hydroxy, an unsubstituted C 1-4 alkoxy, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 3-4 monocyclic cycloalkyl, a fluoro-substituted C 3-4 monocyclic cycloalkyl, a hydroxy-substituted C 3-4 monocyclic cycloalkyl an unsubstituted 4-6 membered monocyclic heterocyclyl, an optionally substituted aryl and an optionally substituted 5-6 membered monocyclic heteroaryl;
R 9 is a substituted phenyl, a substituted monocyclic heteroaryl or a substituted fused-bicyclic heteroaryl, wherein the substituted phenyl, the substituted monocyclic heteroaryl or the substituted fused-bicyclic heteroaryl is substituted with one or more substituents selected from the group consisting of halogen, an unsubstituted C 1-4 alkyl, a cyano-substituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 1-4 alkoxy, a hydroxy-substituted C 1-4 alkoxy, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted monocyclic heteroaryl, an optionally substituted monocyclic heterocyclyl, amino, a mono-substituted amine, a di-substituted amine and —C(═O)NHR 11 ;
R 10A is hydrogen, an unsubstituted C 1-6 alkyl, a monocyclic C 3-6 cycloalkyl optionally substituted with one or two halogens, an optionally substituted 5-6 membered monocyclic heteroaryl, an optionally substituted 4-6 membered monocyclic heterocyclyl or an optionally substituted monocyclic C 3-6 cycloalkyl(C 1-4 alkyl);
R 10B is an optionally substituted C 2-8 alkenyl, wherein the C 2-8 alkenyl is optionally substituted with one or more substituents selected from the group consisting of amino, hydroxy, an unsubstituted C 1-4 alkoxy, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 3-4 monocyclic cycloalkyl, a fluoro-substituted C 3-4 monocyclic cycloalkyl, a hydroxy-substituted C 3-4 monocyclic cycloalkyl and an unsubstituted 4-6 membered monocyclic heterocyclyl;
wherein when R 10A is an optionally substituted monocyclic C 3-6 cycloalkyl(C 1-4 alkyl), then R 10B cannot be an unsubstituted C 2-6 alkenyl; and
R 11 is hydrogen, an unsubstituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl, an optionally substituted C 1-6 alkynyl or an optionally substituted C 3-6 monocyclic cycloalkyl.

2. The compound of claim 1 , wherein Z 1 is —C(═O)—.

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

4. The compound of claim 3 , wherein R 1 is an optionally substituted phenyl.

5. The compound of claim 4 , wherein R 1 is selected from the group consisting of:

6. The compound of claim 5 , wherein R 1 is

7. The compound of claim 6 , wherein R 9 is a substituted phenyl, wherein the phenyl is substituted with —C(═O)NHR 11 ; and R 11 can be an unsubstituted C 1-6 alkyl.

8. The compound of claim 1 , wherein R 2 is hydrogen; R 3 is an unsubstituted C 1-4 alkyl; R 4 is hydrogen; R 5 is hydrogen; R 6 is hydrogen; and R 7 is hydrogen; or wherein R 2 is an unsubstituted C 1-4 alkyl; R 3 is hydrogen; R 4 is hydrogen; R 5 is hydrogen; R 6 is hydrogen; and R 7 is hydrogen.

9. The compound of claim 1 , wherein R 8 is —NR 10A R 10B ; and R 10A is hydrogen.

10. The compound of claim 9 , wherein R 10B is a substituted C 2-8 alkenyl.

11. The compound of claim 9 , wherein R 10B is selected from the group consisting of

12. The compound of claim 9 , wherein R 10B is an unsubstituted C 2-8 alkenyl.

13. The compound of claim 1 , wherein R 8 is an unsubstituted C 2-12 alkynyl; or R 8 is a substituted C 2-12 alkynyl substituted with one or more substituents selected from the group consisting of amino, —NH—C(═O)(an unsubstituted C 1-4 alkyl), hydroxy, an unsubstituted C 1-4 alkoxy, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 3-4 monocyclic cycloalkyl, a fluoro-substituted C 3-4 monocyclic cycloalkyl, a hydroxy-substituted C 3-4 monocyclic cycloalkyl, an unsubstituted 4-6 membered monocyclic heterocyclyl, an optionally substituted aryl and an optionally substituted 5-6 membered monocyclic heteroaryl.

14. The compound of claim 1 , wherein R 9 is a substituted phenyl.

15. The compound of claim 14 , wherein R 9 is substituted with —C(═O)NHR 11 ; and R 11 is an unsubstituted C 1-6 alkyl.

16. The compound of claim 15 , wherein R 9 is substituted with an optionally substituted monocyclic heteroaryl or an optionally substituted monocyclic heterocyclyl.

17. The compound of claim 15 , wherein R 9 is substituted with a substituent selected from the group consisting of halogen, an unsubstituted C 1-4 alkyl, a cyano-substituted C 1-4 alkyl, an optionally substituted monocyclic C 3-6 cycloalkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted C 1-4 alkoxy, a hydroxy-substituted C 1-4 alkoxy, amino, a mono-substituted amine and a di-substituted amine.

18. The compound of claim 1 , wherein R 9 is a substituted monocyclic heteroaryl or a substituted fused-bicyclic heteroaryl.

19. The compound of claim 1 selected from the group consisting of:

Assignees

• Aligos Therapeutics Inc

Inventors

• Vendeville Sandrine
• Raboisson Pierre Jean-Marie Bernard
• Mcgowan David
• Debing Yannick

Classifications

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/513

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• A61K31/522

  having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• A61K31/7072

  having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine · CPC title