IP Library Granted Patent US 11,174,264
Granted Patent B2
US 11,174,264 · App. 16/750,610 · Granted Nov 16, 2021

TYK2 inhibitors and uses thereof

Inventor: Craig E. Masse (Cambridge, MA)
Assignee: Nimbus Lakshmi, Inc.
C07D487/04C07D519/00
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Quick Facts
Patent No.
US 11,174,264
App. No.
16/750,610
Granted
Nov 16, 2021
Kind
B2
Abstract

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.

Claims (33)

1. A compound of formula XX:

or a pharmaceutically acceptable salt thereof, wherein:

R 3 is —C(O)NH 2 , —C(O)NHR 3A , —C(O)N(R 3A ) 2 , —C(O)OR, —C(O)NHOR, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein said ring is substituted with m instances of R 3B ;

R 6 is hydrogen, R A , or R B ;

R 7 is hydrogen, halogen, —NH 2 , —NHR 7A , or —NHC(O)R 7A ;

or R 6 and R 7 are taken together with their intervening atoms to form a 4-7 membered partially unsaturated, or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein said ring is substituted by p instances of R C ;

R 3A , R 3B , and R 7A are each independently R B , and are each substituted by q instances of R C , wherein two R C substituents on the same carbon are optionally taken together to form a 3-6 membered saturated or partially unsaturated spiro-fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or wherein two R C substituents on adjacent carbons are optionally taken together to form a 3-6 membered saturated or partially unsaturated fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each instance of R A is independently oxo, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR)NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R;

each instance of R B is independently C 1-6 aliphatic, phenyl, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3-7 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each instance of R C is independently oxo, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR)NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein two optional substituents on the same carbon are optionally taken together to form a 3-6 membered saturated or partially unsaturated spiro-fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or wherein two optional substituents on adjacent carbons are optionally taken together to form a 3-6 membered saturated or partially unsaturated fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each R is independently hydrogen, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:

two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;

wherein each hydrogen bound to carbon can be optionally and independently replaced by deuterium; and

each instance of m, p, q, and r is independently 0, 1, 2, 3, or .

2. The compound of claim 1 wherein R 7 is —NH 2 or —NHR 7A , or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 wherein each of R 3A and R 7A is independently R B , and is substituted by q instances of R C , provided that neither of R 3A or R 7A is phenyl.

4. The compound of claim 3 wherein R 7A is C 1-6 aliphatic.

5. The compound of claim 4 wherein R 7A is methyl.

6. The compound of claim 1 , wherein R 3 is selected from

7. The compound of claim 1 , wherein R is selected from

8. The compound of claim 1 , wherein R 3 is selected from

9. The compound of claim 8 , wherein R 3 is selected from

10. The compound of claim 1 , wherein R 3 is selected from

11. The compound of claim 1 , wherein R 6 is selected from hydrogen and methyl.

12. The compound of claim 1 , wherein R is selected from —NH 2 , —NHMe, —NHCD 3 ,

13. The compound of claim 1 , wherein R C is selected from

14. The compound of claim 1 , wherein m is 0, 1, 2, or 3.

15. The compound of claim 1 , wherein p is 0, 1, 2, or 3.

16. The compound of claim 1 , wherein q is 0, 1, 2, or 3.

17. The compound of claim 1 , wherein r is 0, 1, 2, or 3.

18. A compound selected from:

or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

Assignments (3)
INTERCOMPANY AGREEMENT Recorded Sep 11, 2023
From: NIMBUS LAKSHMI, INC.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 064867/0415 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 7, 2020
From: MASSE, CRAIG E.
To: NIMBUS DISCOVERY, INC.
Reel/Frame 051752/0874 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 7, 2020
From: NIMBUS DISCOVERY, INC.
To: NIMBUS LAKSHMI, INC.
Reel/Frame 051752/0959 →
Continuity (3)
Provisional Application 62880754 · Jul 31, 2019
Provisional Application 62795735 · Jan 23, 2019
Related Publication 20200231594A1 · Jul 23, 2020
Cited By (1)
US 12,221,453