IP Library › Patent Application 19213418
Patent Application
App. No. 19/213,418

TYK2 INHIBITORS AND USES THEREOF

Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US None
App. No.
19/213,418
Abstract

Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.

Claims (45)

1 . A compound of Formula (IIa) or Formula (IIb):

or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:

L is

wherein Z 1 and Z 2 are each independently selected from the group consisting of —O—, —S—, and —NR Z ; each R Z is independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl; and L 1 and L 2 are each independently C 1 -C 6 alkylene optionally substituted with one or more R L ;

R L is independently selected for each occurrence from the group consisting of deuterium, halogen, —CN, —OR b , —SR b , —S(═O)R a , —S(═O) 2 R a , —NO 2 , —NR c R d , —NHS(═O) 2 R a , —S(═O) 2 NR c R d , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR c R d , —OC(═O)NR c R d , —NR b C(═O)NR c R d , —NR b C(═O)R a , —NR b C(═O)OR b , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or two R L on the same carbon are taken together to form an oxo, a cycloalkyl, or heterocycloalkyl; or two R L on different carbons are taken together to form a cycloalkyl or heterocycloalkyl;

Ring A is selected from the group consisting of, aryl, heteroaryl, and heterocycloalkyl;

R A is independently selected for each occurrence from the group consisting of deuterium, halogen, —CN, —OR b , —SR b , —S(═O)R a , —S(═O) 2 R a , —NO 2 , —NR c R d , —NHS(═O) 2 R a , —S(═O) 2 NR c R d , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR c R d , —OC(═O)NR c R d , —NR b C(═O)NR c R d , —NR b C(═O)R a , —NR b C(═O)OR b , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl may optionally be substituted with one or more R A1 ; or two R A on the same carbon are taken together to form an oxo;

R A1 is independently selected for each occurrence from the group consisting of deuterium, halogen, —CN, —OR b , —SR b , —S(═O)R a , —S(═O) 2 R a , —NO 2 , —NR c R d , —NHS(═O) 2 R a , —S(═O) 2 NR c R d , —C(═O)R a , —OC(═O)R a , —C(═O)OR b , —OC(═O)OR b , —C(═O)NR c R d , —OC(═O)NR c R d , —NR b C(═O)NR c R d , —NR b C(═O)R a , —NR b C(═O)OR b , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or two R A1 on the same carbon are taken together to form an oxo;

n is 0-4;

Y 8 is N;

Y 6 is CR 6 ;

Y 3 is CR 3 ;

Y 9 is N;

R 3 and R 6 — are each hydrogen;

R 4 is independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl may optionally be substituted with one or more R 4a ;

R 4a is independently selected for each occurrence from the group consisting of deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or two R 4a on the same carbon are taken together to form an oxo;

R 5 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 deuteroalkyl;

R 7 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 deuteroalkyl;

R a is independently selected for each occurrence from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl may optionally be substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

R b is independently selected for each occurrence from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl may optionally be substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl; and

R c and R d are independently selected for each occurrence from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 aminoalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl may optionally be substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

or R c and R d are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH 2 , —C(═O)Me, —C(═O)OH, —C(═O)OMe, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.

2 .- 11 . (canceled)

12 . The compound of claim 1 , wherein R 4 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 deuteroalkyl.

13 . The compound of claim 1 , wherein R 4 is selected from the group consisting of C 1 -C 6 alkyl and C 1 -C 6 deuteroalkyl.

14 . The compound of claim 1 , wherein R 5 is hydrogen.

15 . The compound of claim 1 , wherein R 7 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl.

16 . The compound of claim 1 , wherein Ring A is selected from the group consisting of aryl and heteroaryl.

17 . The compound of claim 1 , wherein Ring A is phenyl.

18 . The compound of claim 1 , wherein Ring A is selected from the group consisting of pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, benzoxazolyl, and benzoisoxazole.

19 . The compound of claim 1 , wherein R A is independently selected for each occurrence from the group consisting of deuterium, halogen, —CN, —OR b , —NR c R d , —C(═O)R a , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 deuteroalkyl.

20 .- 27 . (canceled)

28 . The compound of claim 1 , wherein R L is independently selected for each occurrence from the group consisting of deuterium, halogen, —CN, —OR b , —NR c R d , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 deuteroalkyl; or two R L on the same carbon are taken together to form an oxo.

29 . The compound of claim 1 , wherein R L is independently selected for each occurrence from the group consisting of deuterium, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 deuteroalkyl; or two R L on the same carbon are taken together to form an oxo or a cycloalkyl; or two R L on different carbons are taken together to form a cycloalkyl.

30 . The compound of claim 1 , wherein R L is independently selected for each occurrence from the group consisting of deuterium, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 deuteroalkyl; or two R L on the same carbon are taken together to form an oxo.

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

32 . (canceled)

33 . The compound of claim 1 , wherein L is

34 . A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

35 . A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.

36 . A method of inhibiting tyrosine kinase 2 activity a patient in need thereof, comprising administering to the patient an effective amount of a compound of claim 1 .

37 . A method of treating a tyrosine kinase 2-mediated disorder in a patient in need thereof, comprising administering to the patient an effective amount of a compound of claim 1 .

38 . The method of claim 37 , wherein the tyrosine kinase 2-mediated disorder is selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, and a disorder associated with transplantation.

39 . The method of claim 37 , wherein the disorder is associated with type I interferon, IL-10, IL-12, or IL-23 signaling.