Chromobox protein inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-2025034126-A1
Application number	US-202418898034-A
Country	US
Kind code	A1
Filing date	Sep 26, 2024
Priority date	Sep 26, 2016
Publication date	Jan 30, 2025
Grant date	—

Abstract

Provided herein are compounds useful as inhibitors of CBX. Also described are pharmaceutical compositions and medical uses of these compounds.

First claim

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

wherein
R 1 is optionally substituted aryl or heteroaryl;
R 2 is H, halo, optionally substituted aryl, or optionally substituted heteroaryl;
L 1 is —C(O)—, —C(O)NH—, optionally substituted —C(O)NH-alkylene-, or —C(O)NHNCH—; and
A is OH or optionally substituted heterocyclyl, aryl, or heteroaryl.

2 . The compound of claim 1 , wherein R 1 is

3 . The compound of any preceding claim wherein R 2 is Br.

4 . The compound of any one of claims 1 or 2 , wherein R 2 is

5 . The compound of any preceding claim wherein A is

6 . The compound of any preceding claim wherein L 1 is

7 . The compound of claim 6 wherein L 1 -A is

8 . The compound of any one of claims 1-5 , wherein L 1 is

9 . The compound of claim 8 , wherein L 1 -A is

10 . The compound of any preceding claim , wherein the compound is not

11 . A compound having a structure of Formula II or a pharmaceutically acceptable salt thereof:

wherein
R 3 is optionally substituted aryl, heteroaryl, —C(O)-aryl, alkyl, or alkoxycarbonyl;
R 4 is optionally substituted alkyl, aryl or heteroaryl; and
L 2 is ═N—C(O)—, ═N—NCH—, ═N—, or ═N—NH—.

12 . The compound of claim 11 , wherein R 3 is

13 . The compound of any one of claims 11 or 12 , wherein R 4 is

14 . The compound of any one of claims 12-13 , wherein L 2 is

15 . The compound of any one of claims 12-14 , wherein the compound is not

16 . A compound have a structure of Formula II or a pharmaceutically acceptable salt thereof:

wherein
R 5 is optionally substituted aryl or heteroaryl;
R 6 is —C(O)NH—NCH—R 7 or —C(O)O-alkyl; and
R 7 is optionally substituted aryl or heteroaryl.

17 . The compound of claim 16 , wherein R 5 is

18 . The compound of any one of claims 16 or 17 , wherein R 7 is

19 . The compound of any one of claims 16 or 17 , wherein R 6 is

20 . A compound having a structure of Formula IV or V or a pharmaceutically acceptable salt thereof:

wherein
R 8 is optionally substituted alkyl, aryl, or heteroaryl;
R 9 is optionally substituted aryl or heteroaryl;
L 3 is —NH—CO—NH—, —NH—CO—, —NH—NCH 2 —, —NH—, —CH 2 —, or —CH 2 —NH—CO—; and
L 4 is absent or is

21 . The compound of claim 20 , wherein R 8 is

22 . The compound of any one of claims 20 or 21 , wherein R 9 is

23 . The compound of any one of claims 20-22 , wherein L 3 -R 9 is —NH—CO—NH—R 9 , —NH—CO—R 9 , —NH—NCH 2 —R 9 , or —CH 2 —NH—CO—R 9 .

24 . The compound of any one of claims 20-23 , wherein L 4 is

25 . A compound having a structure of Formula VI or a pharmaceutically acceptable salt thereof:

wherein
R 10 is optionally substituted alkyl, aryl or heteroaryl; and
R 11 is optionally substituted aryl or heteroaryl.

26 . The compound of claim 25 , wherein R 10 is

27 . The compound of any one of claims 25 or 26 , wherein R 11 is

28 . A compound having a structure of Formula VII or a pharmaceutically acceptable salt thereof:

wherein
R 12 is optionally substituted alkyl, aryl or heteroaryl; and
R 13 is optionally substituted aryl or heteroaryl.

29 . The compound of claim 28 , wherein R 13 is

30 . The compound of any one of claims 28 or 29 , wherein R 12 is

31 . A compound having a structure of Formula VIII or a pharmaceutically acceptable salt thereof:

wherein R 14 is optionally substituted alkyl or aryl.

32 . The compound of claim 31 , wherein R 14 is -ethyl

33 . The compound of any one of claims 31 or 32 , wherein the compound is not

Assignees

• Dana Farber Cancer Inst Inc

Inventors

• Bradner James E
• Qi Jun
• Federation Alexander
• Jacobson Zoe
• Varca Anthony

Classifications

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D277/54

  Nitrogen and either oxygen or sulfur atoms · CPC title

• A61P35/00

  Antineoplastic agents · CPC title