IP Library › Granted Patent US 12709628
Granted Patent B2
US 12709628 · App. 19/267,357 · Granted Aug 18, 2026

STAT6 modulators and uses thereof

Inventors: Howard Bregman (Melrose, MA); John Yeoman (Medford, MA); Jennifer Downing (Clinton, MA); Samuel K. Reznik (Cambridge, MA); Ernest Allen Sickmier (Needham, MA); Giovanni Cianchetta (Boxford, MA); Rishi G. Vaswani (Lexington, MA); Neil Bifulco (Sudbury, MA); Xia Tian (Cambridge, MA); Andrew Tasker (Simi Valley, CA); Brian Hodous (Arlington, MA)
Assignee: Recludix Pharma, Inc.
C07F9/6561A61K31/675
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Quick Facts
Patent No.
US 12709628
App. No.
19/267,357
Granted
Aug 18, 2026
Kind
B2
Abstract

The present disclosure relates generally to STAT6 modulators and uses thereof, and more specifically to compounds, salts, and compositions thereof useful for treating conditions associated with STAT6.

Claims (144)

1 . A compound of Formula (I),

or a pharmaceutically acceptable salt thereof, wherein:

R 1a and R 1b are each independently H or halogen;

R 2 is H, (C 1 -C 6 )alkyl, or (C 3 -C 6 )cycloalkyl;

R 3 is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, 3- to 7-membered heterocyclyl, —(C 1 -C 6 )alkylene-(C 3 -C 6 )cycloalkyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 6 )cycloalkyl, or (3- to 7-membered heterocyclyl) of —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl) is each substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, cyano, halogen, halo(C 1 -C 6 )alkyl, and halo(C 1 -C 6 )alkoxy;

R 4 is H, (C 6 -C 10 )aryl, or 5- to 10-membered heteroaryl, wherein (C 6 -C 10 )aryl or 5- to 10-membered heteroaryl is each substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, and —NR 4a R 4b , wherein:

each R 4a and R 4b is independently H or (C 1 -C 6 )alkyl;

R 5 is H;

R P is;

R P1 and R P2 are each independently —OH, —OR Pa , N-linked amino acid, N-linked amino acid ester, or

 wherein

 is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and —C(O)OR PE ;

each R Pa is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, or (C 3 -C 6 )cycloalkyl, wherein (C 1 -C 6 )alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (C 1 -C 6 )alkoxy; and

each R PE is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 6 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3- to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R P1 is —OR Pa and R P2 is N-linked amino acid ester, wherein:

N-linked amino acid ester is —NR Paa1 CR Paa2 R Paa3 C(O)OR Paa4 ;

R Paa1 is H or (C 1 -C 6 )alkyl;

R Paa2 is H or (C 1 -C 6 )alkyl, and R Paa3 is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl; or R Paa2 and R Paa3 , together with the carbon atom to which they are attached, form (C 3 -C 6 )cycloalkyl; and

R Paa4 is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3- to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

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

or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R P1 and R P2 are each —OH.

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

 or a pharmaceutically acceptable salt thereof.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R P1 is —OH and R P2 is N-linked amino acid, wherein:

N-linked amino acid is —NR Paa1 CR Paa2 R Paa3 C(O)OH;

R Paa1 is H or (C 1 -C 6 )alkyl;

R Paa2 is H or (C 1 -C 6 )alkyl; and

R Paa3 is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy;

or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl; or R Paa2 and R Paa3 , together with the carbon atom to which they are attached, form (C 3 -C 6 )cycloalkyl.

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

or a pharmaceutically acceptable salt thereof.

8 . The compound of claim 1 , wherein the compound is of Formula (I-C-3),

or a pharmaceutically acceptable salt thereof, wherein:

R Pa is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, or (C 3 -C 6 )cycloalkyl, wherein (C 1 -C 6 )alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (C 1 -C 6 )alkoxy;

R Paa2 is H or (C 1 -C 6 )alkyl;

R Paa3 is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl; or

R Paa2 and R Paa3 , together with the carbon atom to which they are attached, form (C 3 -C 6 )cycloalkyl; and

R Paa4 is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3- to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

9 . The compound of claim 1 , wherein the compound is of Formula (I-C-5),

or a pharmaceutically acceptable salt thereof, wherein:

R Pa is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, or (C 3 -C 6 )cycloalkyl, wherein (C 1 -C 6 )alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (C 1 -C 6 )alkoxy;

R Paa2 is H or (C 1 -C 6 )alkyl;

R Paa3 is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl; or

R Paa2 and R Paa3 , together with the carbon atom to which they are attached, form (C 3 -C 6 )cycloalkyl; and

R Paa4 is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3- to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

10 . The compound of claim 1 , wherein the compound is of Formula (I-A-3),

or a pharmaceutically acceptable salt thereof.

11 . The compound of claim 1 , wherein the compound is of Formula (I-A-5),

or a pharmaceutically acceptable salt thereof.

12 . The compound of claim 1 , wherein the compound is of Formula (I-B-3),

or a pharmaceutically acceptable salt thereof, wherein:

R Paa2 is H or (C 1 -C 6 )alkyl; and

R Paa3 is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl; or

R Paa2 and R Paa3 , together with the carbon atom to which they are attached, form (C 3 -C 6 )cycloalkyl.

13 . The compound of claim 1 , wherein the compound is of Formula (I-B-5),

or a pharmaceutically acceptable salt thereof, wherein:

R 1a is F;

R Paa2 is H or (C 1 -C 6 )alkyl; and

R Paa3 is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl; or

R Paa2 and R Paa3 , together with the carbon atom to which they are attached, form (C 3 -C 6 )cycloalkyl.

14 . The compound of claim 1 , wherein the compound is of Formula (I-H-3),

or a pharmaceutically acceptable salt thereof, wherein:

R P1 and R P2 are each independently —OH, —OR Pa , —NR Paa1 CR Paa2 R Paa3 C(O)OH, —NR Paa1 CR Paa2 R Paa3 C(O)OR Paa4 , or Ring A;

Ring A is

 substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and —C(O)OR PE ;

each R Pa is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, or (C 3 -C 6 )cycloalkyl, wherein (C 1 -C 6 )alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (C 1 -C 6 )alkoxy;

each R PE is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3- to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen;

each R Paa1 is independently H or (C 1 -C 6 )alkyl; each R Paa2 is independently H or (C 1 -C 6 )alkyl;

each R Paa3 is independently H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl;

or R Paa2 and R Paa3 , together with the carbon atom to which they are attached form (C 3 -C 6 )cycloalkyl;

and each R Paa4 is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3- to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

15 . The compound of claim 14 , wherein the compound is of Formula (I-H-5),

or a pharmaceutically acceptable salt thereof.

16 . The compound of claim 1 , wherein the compound is of Formula (I-H-4),

or a pharmaceutically acceptable salt thereof, wherein:

R P1 and R P2 are each independently —OH, —OR Pa , —NR Paa1 CR Paa2 R Paa3 C(O)OH, —NR Paa1 CR Paa2 R Paa3 C(O)OR Paa4 , or Ring A;

Ring A is

 substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo, oxo, COOH, and —C(O)O PE ;

each R Pa is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, or (C 3 -C 6 )cycloalkyl, wherein (C 1 -C 6 )alkyl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halo and (C 1 -C 6 )alkoxy;

each R PE is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3-to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen;

each R Paa1 is independently H or (C 1 -C 6 )alkyl; each R Paa2 is independently H or (C 1 -C 6 )alkyl;

each R Paa3 is independently H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, or —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl;

or R Paa2 and R Paa3 , together with the carbon atom to which they are attached form (C 3 -C 6 )cycloalkyl;

and each R Paa4 is independently (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-(C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, —(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl, 3-to 7-membered heterocyclyl, or —(C 1 -C 6 )alkylene-(3- to 7-membered heterocyclyl), wherein (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 5 -C 8 )spirocycloalkyl, or (C 3 -C 7 )cycloalkyl of —(C 1 -C 6 )alkylene-(C 3 -C 7 )cycloalkyl is each substituted with 0, 1, 2, or 3 independently selected halogen.

17 . The compound of claim 16 , wherein the compound is of Formula (I-H-6),

or a pharmaceutically acceptable salt thereof.

18 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2 is (C 1 -C 6 )alkyl; and R 3 is halo(C 1 -C 6 )alkyl.

19 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 2 is (C 1 -C 6 )alkyl; and R 3 is halo(C 1 -C 6 )alkyl.

20 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2 is (C 1 -C 6 )alkyl; and R 3 is (C 3 -C 6 )cycloalkyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, halo(C 1 -C 6 )alkyl, and halo(C 1 -C 6 )alkoxy.

21 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 2 is (C 1 -C 6 )alkyl; and R 3 is (C 3 -C 6 )cycloalkyl substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of halogen, cyano, halo(C 1 -C 6 )alkyl, and halo(C 1 -C 6 )alkoxy.

22 . The compound of claim 2 , wherein

 of formula (I) is

23 . The compound of claim 4 , wherein

 of Formula (I) is

24 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R Pa is phenyl; R Paa1 is H; R Paa2 is H; R Paa3 is (C 1 -C 6 )alkyl; and R Paa4 is (C 1 -C 6 )alkyl.

25 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R Pa is phenyl; R Paa1 is H; R Paa2 is H; R Paa3 is methyl; and R Paa4 is

26 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

27 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

28 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

29 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

30 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

31 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

32 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

33 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

34 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

35 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

36 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

37 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

38 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

39 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

40 . A compound having the structure:

or a pharmaceutically acceptable salt thereof.

41 . A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

42 . A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

43 . A pharmaceutical composition comprising the compound of claim 3 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

44 . A pharmaceutical composition comprising the compound of claim 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

45 . A pharmaceutical composition comprising the compound of claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

46 . A pharmaceutical composition comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

47 . A pharmaceutical composition comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

48 . A pharmaceutical composition comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

49 . A pharmaceutical composition comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

50 . A pharmaceutical composition comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.