Bicyclic sulfonamides

Patent metadata

Field	Value
Publication number	US-11033556-B2
Application number	US-202016789298-A
Country	US
Kind code	B2
Filing date	Feb 12, 2020
Priority date	Feb 14, 2019
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

Provided herein are compounds of Formulae (I) and (II), or pharmaceutically acceptable salts of the foregoing, 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 Formulae (I) and/or (II), or a pharmaceutically acceptable salt of any of the foregoing.

First claim

What is claimed is:

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

wherein:
is a single or a double bond,
wherein when is a single bond, then Z 1 is CR 8A R 9A and Z 2 is CR 8B R 9B ; and
wherein when is a double bond, then Z 1 and Z 2 are each independently CR 10 ;

R 1 is a substituted or an unsubstituted C 2-8 alkenyl or a substituted or an unsubstituted C 2-8 alkynyl, wherein the substituted C 2-8 alkenyl and the substituted C 2-8 alkynyl is substituted with one or more substituents independently selected from halogen, hydroxy, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted bicyclic C 3-8 cycloalkyl, an optionally substituted monocyclic heterocyclyl and R 11A ;
R 2 is hydrogen, deuterium or a substituted or an unsubstituted C 1-4 alkyl, wherein the substituted C 1-4 alkyl is substituted with one or more substituents selected from halogen, hydroxy and R 11B ;
R 3 is hydrogen, deuterium or an unsubstituted C 1-4 alkyl;
R 4 is hydrogen, deuterium or an unsubstituted C 1-4 alkyl;
R 5 is hydrogen, deuterium, halogen, an unsubstituted C 1-4 alkyl, cyano, an unsubstituted C 1-4 haloalkyl or an unsubstituted C 3-8 monocyclic cycloalkyl;
R 6 is a substituted phenyl or a substituted pyridyl, wherein the substituted phenyl and the substituted pyridyl is substituted with one or more substituents independently selected from halogen, cyano, an unsubstituted C 1-4 haloalkyl and an unsubstituted C 1-4 alkyl; and
R 7 is hydrogen, deuterium or an unsubstituted C 1-4 alkyl;
R 8A , R 8B , R 9A and R 9B are independently hydrogen, deuterium, halogen, an unsubstituted C 1-4 alkyl or hydroxy;
each R 10 are independently hydrogen, deuterium, halogen or an unsubstituted C 1-4 alkyl; and
R 11A and R 11B are independently an optionally substituted —O-acyl, an unsubstituted O-linked α-amino acid, —O—P(═O)(OH) 2 or —CH 2 —P(═O)(OH) 2 .

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein is a single or a double bond; Z 1 is CR 8A R 9A ; Z 2 is CR 8B R 9B ; R 8A is hydrogen; R 9A is hydrogen; R 8B is hydrogen; and R 9B is hydrogen.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein is a double bond, Z 1 and Z 2 are each independently CR 10 ; and R 10 is hydrogen.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is an unsubstituted C 2-8 alkenyl or an unsubstituted C 2-8 alkynyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is a substituted C 2-8 alkenyl, wherein the substituted C 2-8 alkenyl is substituted with one or more substituents independently selected from halogen, hydroxy, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted bicyclic C 3-8 cycloalkyl, an optionally substituted monocyclic heterocyclyl and R 11A ; or wherein R 1 is a substituted C 2-8 alkynyl, wherein the substituted C 2-8 alkynyl is substituted with one or more substituents independently selected from halogen, hydroxy, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted bicyclic C 3-8 cycloalkyl, an optionally substituted monocyclic heterocyclyl and R 11A .

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen.

7. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 2 is an unsubstituted C 1-4 alkyl or a substituted C 1-4 alkyl.

8. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 3 is hydrogen.

9. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 4 is an unsubstituted C 1-4 alkyl.

10. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 5 is hydrogen.

11. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 7 is hydrogen.

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

wherein:
R 12 is a substituted or an unsubstituted C 2-8 alkenyl or a substituted or an unsubstituted C 2-8 alkynyl, wherein the substituted C 2-8 alkenyl and the substituted C 2-8 alkynyl is substituted with one or more substituents independently selected from halogen, hydroxy, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted bicyclic C 3-8 cycloalkyl, an optionally substituted monocyclic heterocyclyl and R 19A ;
R 13 is hydrogen, deuterium or a substituted or an unsubstituted C 1-4 alkyl, wherein the substituted C 1-4 alkyl is substituted with one or more substituents selected from halogen, hydroxy and R 19B ;
R 14 is hydrogen, deuterium or an unsubstituted C 1-4 alkyl;
R 15 is hydrogen, deuterium or an unsubstituted C 1-4 alkyl;
R 16 is hydrogen, deuterium, halogen, an unsubstituted C 1-4 alkyl, cyano, an unsubstituted C 1-4 haloalkyl or an unsubstituted C 3-8 monocyclic cycloalkyl;
R 17 is a substituted phenyl or a substituted pyridyl, wherein the substituted phenyl and the substituted pyridyl is substituted with one or more substituents independently selected from halogen, cyano, an unsubstituted C 1-4 haloalkyl and an unsubstituted C 1-4 alkyl;
R 18 is hydrogen, deuterium or an unsubstituted C 1-4 alkyl; and
R 19A and R 19B are independently an optionally substituted —O-acyl, an unsubstituted O-linked α-amino acid, —O—P(═O)(OH) 2 or —CH 2 —P(═O)(OH) 2 ; and
provided that when R 12 is an unsubstituted 2-butynyl, R 13 is hydrogen, R 14 and R 18 are each hydrogen, R 15 is methyl and R 16 is hydrogen, then R 17 is not 3,4-difluorophenyl.

13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 12 is an unsubstituted C 2-8 alkenyl or an unsubstituted C 2-8 alkynyl.

14. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 12 is a substituted C 2-8 alkenyl, wherein the substituted C 2-8 alkenyl is substituted with one or more substituents independently selected from halogen, hydroxy, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted bicyclic C 3-8 cycloalkyl, an optionally substituted monocyclic heterocyclyl and R 19A ; or wherein R 12 is a substituted C 2-8 alkynyl, wherein the substituted C 2-8 alkynyl is substituted with one or more substituents independently selected from halogen, hydroxy, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted bicyclic C 3-8 cycloalkyl, an optionally substituted monocyclic heterocyclyl and R 19A .

15. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 13 is hydrogen.

16. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 13 is an unsubstituted C 1-4 alkyl or a substituted C 1-4 alkyl.

17. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 14 is hydrogen.

18. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 15 is an unsubstituted C 1-4 alkyl.

19. The c

Assignees

• Aligos Therapeutics Inc

Inventors

• Beigelman Leonid
• Smith David Bernard

Classifications

• C07D515/04

  Ortho-condensed systems · CPC title

• C07D513/04 Primary

  Ortho-condensed systems · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P31/14 Primary

  for RNA viruses · CPC title

• A61K31/554 Primary

  having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem · CPC title