Granted Patent B2

US 12,667,572 · App. 18/273,879 · Granted Jun 30, 2026

Inventors: Shulu Feng (New York, NY); Morgan Lawrenz (New York, NY); Jiaye Guo (New York, NY); Goran Krilov (New York, NY); Andrew Placzek (New York, NY); Zhe Nie (New York, NY); Lynnie Trzoss (New York, NY); Haifeng Tang (New York, NY); Pieter Harm Bos (New York, NY); Michael Trzoss (New York, NY); Shelby Ellery (New York, NY)

Assignee: SCHRÖDINGER, INC.

A61K31/519A61K31/4427A61K31/444A61K31/5025A61K45/06C07D471/04C07D487/04C07D491/12C07D491/20G01N33/573G01N33/6869G01N2333/5428G01N2333/95G01N2800/52

Abstract

Claims (89)

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

each is a single or double bond;

Q is —CH 2 —, O, or NH;

X is N or C;

Y is N or C;

Z is N or CRS;

wherein when one of X and Y is N, the other of X and Y is C;

R X is hydrogen or halogen;

n is 1, 2, or 3;

R 1 is hydrogen, halogen, cyano, hydroxyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 haloalkyl, —NR A R B , or C1-C3 alkyl optionally substituted with 1-3 substituents selected from hydroxyl and C1-C3 alkoxy;

R 2 is hydrogen, halogen, amino, or C1-C3 alkyl;

each R 3 is independently deuterium, halogen, hydroxyl, C3-C6 cycloalkyl, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or C1-C3 haloalkyl; or two R 3 together with the carbon atom to which they are attached come together to form an oxo group, a 4-8 membered heterocyclyl, or a C3-C8 cycloalkyl;

m is 0, 1, 2, or 3;

R 4 is phenyl or 5-9 membered heteroaryl; wherein each R 4 group is optionally substituted with 1-3 substituents independently selected from R 6 ;

R 5 is hydrogen, halogen, cyano, hydroxyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 haloalkyl, —NR C R D , or C1-C3 alkyl; and

each R 6 is independently selected from halogen; cyano; amino; —N=(S═O)(C1-C3 alkyl) 2 ; —S(═O) p (C1-C3 alkyl); —(C═O)NR E R F ; C1-C3 alkoxy; C1-C3 haloalkyl optionally substituted with hydroxyl; C1-C3 haloalkoxy; 5-6 membered heteroaryl optionally substituted with halogen, cyano, hydroxyl, C1-C3 alkoxy, C1-C3 haloalkoxy, amino, C1-C3 haloalkyl, 4-6 membered heterocyclyl, or C1-C3 alkyl optionally substituted with hydroxyl or —NR E R F ; C1-C4 alkyl optionally substituted with hydroxyl, —NR E R F , or C1-C3 alkoxy; 3-8 membered heterocyclyl; and C3-C6 cycloalkoxy;

p is 1 or 2; and

R A , R B , R C , R D , R E , and R F , are independently hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl, or

R A and R B , or R C and R D , or R E and R F , together with the nitrogen atom to which they are attached come together to form a 4-6 membered heterocyclyl optionally substituted with 1-2 halogens.

2 . The compound of claim 1 , wherein;

X is C and Y is C; or

X is N and Y is C; or

X is C and Y is N.

3 . The compound of claim 1 , wherein Z is N.

4 . The compound of claim 1 , wherein Z is CR 5 .

5 . The compound of claim 1 , wherein Q is —CH 2 —.

6 . The compound of claim 1 , wherein Q is O.

7 . The compound of claim 1 , wherein R 1 is hydrogen, halogen, cyano, hydroxyl, C1-C3 haloalkyl, or C1-C3 alkyl optionally substituted with 1-3 substituents selected from hydroxyl and C1-C3 alkoxy.

8 . The compound of claim 1 , wherein R 1 is hydrogen, halogen, or C1-C3 alkyl.

9 . The compound of claim 1 , wherein n is 1 or 2.

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

11 . The compound of claim 1 , wherein each R 3 is independently deuterium, halogen, hydroxyl, C3-C6 cycloalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, or C1-C3 haloalkoxy.

12 . The compound of claim 1 , wherein:

m is 2 and each R 3 is methyl; or

m is 2 and one R 3 is methyl and the other R 3 is trifluoromethyl; or

m is 2 and one R 3 is trifluoromethyl and the other R 3 is ethoxy; or

m is 2 and the two R 3 together with the carbon atom to which they are attached come together to form a 4-8 membered heterocyclyl, optionally wherein the 4-8 membered heterocyclyl is oxetanyl or tetrahydropyranyl; or

m is 2 and the two R 3 together with the carbon atom to which they are attached form a C3-C8 cycloalkyl, optionally wherein the C3-C8 cycloalkyl is cyclopropyl or cyclobutyl; or

m is 3; two R 3 are methyl, and one R 3 is selected from the group consisting of methyl and hydroxyl.

13 . The compound of claim 1 , wherein R 4 is 5-9 membered heteroaryl optionally substituted with 1-3 independently selected R 6 .

14 . The compound of claim 1 , wherein:

(i) at least one of R 6 is halogen; or

(ii) at least one of R 6 is cyano; or

(iii) at least one of R 6 is —(C═O)NR E R F , optionally wherein:

R E and R F are independently hydrogen, C1-C3 alkyl, or C3-C6 cycloalkyl; or

one of R E and R F is hydrogen and the other of R E and R F is C1-C3 alkyl or C3-C6 cycloalkyl; or

one of R E and R F is C1-C3 alkyl and the other of R E and R F is C3-C6 cycloalkyl; or

R E and R F together with the nitrogen atom to which they are attached come together to form a 4-6 membered heterocyclyl optionally substituted with 1-2 halogens; or

(iv) at least one of R 6 is —N=(S═O)(C1-C3 alkyl) 2 ; or

(v) at least one of R 6 is C1-C3 alkoxy; or

(vi) at least one of R 6 is C1-C3 haloalkyl optionally substituted with hydroxyl; or

(vii) at least one of R 6 is C1-C3 haloalkoxy; or

(viii) at least one of R 6 is 5-6 membered heteroaryl optionally substituted with halogen, cyano, hydroxyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl optionally substituted with hydroxyl or —NR E R F , amino, or C1-C3 haloalkyl; or

(ix) at least one of R 6 is C1-C4 alkyl optionally substituted with hydroxyl, —NR E R F , or C1-C3 alkoxy; or

(x) at least one of R 6 is 3-8 membered heterocyclyl; or

(xi) at least one of R 6 is C3-C6 cycloalkoxy; or

(xii) at least one of R 6 is cyclopropoxy.

15 . The compound of claim 1 , wherein R 4 is 3-pyridyl or 4-pyridyl substituted with 1-3 independently selected R 6 .

16 . The compound of claim 1 ,

wherein R 4 is

 wherein the wavy line crosses the bond that connects to the —C(═O)NH— moiety of Formula (I).

17 . The compound of claim 16 , wherein R 6 is selected from the group consisting of cyano, halogen, C1-C3 haloalkyl optionally substituted with hydroxyl, C1-C3 haloalkoxy, and C1-C3 alkoxy.

18 . The compound of claim 1 ,

wherein R 4 is

 wherein R 6A and R 6B are independently selected from R 6 and the wavy line crosses the bond that connects to the —C(═O)NH— moiety of Formula (I).

19 . The compound of claim 18 , wherein

R 6A is selected from the group consisting of: cyano, halogen, C1-C3 alkyl, C1-C3 alkoxy, and C1-C3 haloalkyl; and

R 6B is selected from the group consisting of: 5-6 membered heteroaryl optionally substituted with cyano, C1-C3 alkyl optionally substituted with hydroxyl, 4-6 membered heterocyclyl, or amino; —N=(S═O)(C1-C3 alkyl) 2 ; —(C═O)NR E R F ; C1-C3 alkoxy; C1-C3 haloalkyl optionally substituted with hydroxyl; C1-C3 haloalkoxy; cyano; C3-C6 cycloalkoxy; and C1-C3 alkyl optionally substituted with hydroxyl.

20 . The compound of claim 1 ,

wherein R 4 is

 wherein R 6A , R 6B , and R 6C are independently selected from R 6 and the wavy line crosses the bond that connects to the —C(═O)NH— moiety of Formula (I).

21 . The compound of claim 20 , wherein

R 6A is selected from the group consisting of: cyano, halogen, C1-C3 alkyl, C1-C3 alkoxy, and C1-C3 haloalkyl;

R 6B is selected from the group consisting of: 5-6 membered heteroaryl optionally substituted with cyano, C1-C3 alkyl, or amino; —(C═O)NR E R F ; C1-C3 alkoxy; C1-C3 haloalkyl; C1-C3 haloalkoxy; cyano; and C1-C3 alkyl; and

R 6C is selected from the group consisting of: cyano, halogen, C1-C3 alkyl, C1-C3 alkoxy, and C1-C3 haloalkyl.

22 . The compound of claim 1 , wherein R 5 is hydrogen or halogen, optionally wherein the halogen is fluoro.

23 . The compound of claim 1 , wherein R X is halogen, optionally wherein the halogen is fluoro.

24 . The compound of claim 1 , wherein R X is hydrogen.

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

or a pharmaceutically acceptable salt thereof.

26 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

27 . A method for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

28 . A method of treating a MALT1-associated cancer in a subject, comprising administering to a subject identified or diagnosed as having a MALT1-associated cancer an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

29 . The method of claim 27 , further comprising administering an additional therapy or therapeutic agent to the subject.

30 . A method for treating an autoimmune disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

31 . A method of treating a MALT1-associated autoimmune disorder in a subject, comprising administering to a subject identified or diagnosed as having a MALT1-associated autoimmune disorder an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

32 . A method for treating an inflammatory disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

33 . A method of treating a MALT1-associated inflammatory disorder in a subject, comprising administering to a subject identified or diagnosed as having a MALT1-associated inflammatory disorder an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (4)

References Cited (400)