Inhibiting CREB binding protein (CBP)

Patent metadata

Field	Value
Publication number	US-12378242-B2
Application number	US-202217669112-A
Country	US
Kind code	B2
Filing date	Feb 10, 2022
Priority date	Jun 29, 2018
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

The present disclosure is directed to inhibitors of the CBP/p300 family of bromodomains. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP/p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP/p300 family of bromodomains, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of CBP/p300 family of bromodomains, and methods of synthesis of these compounds.

First claim

What is claimed is:

1. A compound according to the following formula:

or a pharmaceutically acceptable salt or enantiomer thereof, wherein:
R 1 is —OR 5 ;
R 5 is —C 1 -C 6 alkyl, —C 3 -C 8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
R 6 is —C 3 -C 8 cycloalkyl, —C 4 -C 8 cycloalkenyl, heterocyclyl, heteroaryl, aryl, wherein each cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more —R 10 ;
R 6′ is —C 1 -C 6 alkyl-C 1 -C 2 alkyl;
R 7 is —H at one occurrence, and —C(O) OH or —C(O)OC 1 -C 6 alkyl at the other occurrence;
R 10 is independently, at each occurrence, —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 6 cycloalkyl, —C 4 -C 8 cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO 2 , —CN, —NH 2 , —OC 1 -C 6 alkyl, —OC 3 -C 6 cycloalkyl, -Oaryl, -Oheteroaryl, —NHC 1 -C 6 alkyl, —N(C 1 -C 6 alkyl) 2 , —S(O) 2 NH(C 1 -C 6 alkyl), —S(O) 2 N(C 1 -C 6 alkyl) 2 , —S(O) 2 C 1 -C 6 alkyl, —C(O)C 1 -C 6 alkyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 alkyl), —NHC(O)C 1 -C 6 alkyl, —C(O)N(C 1 -C 6 alkyl) 2 , —C(O)OC 1 -C 6 alkyl, —N(C 1 -C 6 alkyl) SO 2 C 1 -C 6 alkyl, —S(O) (C 1 -C 6 alkyl), —S(O)N(C 1 -C 6 alkyl) 2 , or —N(C 1 -C 6 alkyl)S(O)(C 1 -C 6 alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more —R 12 ; and
R 12 is independently, at each occurrence, —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 8 cycloalkyl, —C 4 -C 8 cycloalkenyl, heterocyclyl, heteroaryl, aryl, —OH, halogen, oxo, —NO 2 , —CN, —NH 2 , —OC 1 -C 6 alkyl, —NHC 1 -C 6 alkyl, —N(C 1 -C 6 alkyl) 2 , —S(O) 2 NH(C 1 -C 6 alkyl), —S(O) 2 N(C 1 -C 6 alkyl) 2 , —S(O) 2 C 1 -C 6 alkyl, —C(O)C 1 -C 6 alkyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 alkyl), —C(O)N(C 1 -C 6 alkyl) 2 , —C(O)OC 1 -C 6 alkyl, —N(C 1 -C 6 alkyl) SO 2 C 1 -C 6 alkyl, —S(O) (C 1 -C 6 alkyl), —S(O)N(C 1 -C 6 alkyl) 2 , or —N(C 1 -C 6 alkyl)S(O)(C 1 -C 6 alkyl).

2. The compound of claim 1 , wherein R 5 is —C 1 -C 6 alkyl.

3. The compound of claim 1 , wherein R 5 is methyl.

4. The compound of claim 1 , wherein q is 1.

5. The compound of claim 1 , wherein R 7 is —H at one occurrence and —C(O)OH at the other occurrence.

6. The compound of claim 1 , wherein m is 3, q is 1, and R 7 is —C(O) OH.

7. The compound of claim 1 , wherein R 6′ is —C 1 -C 3 alkyl.

8. The compound of any one of claim 1 , wherein R 6′ is selected from methyl and ethyl.

9. The compound of claim 1 , wherein R 6 is selected from aryl and heteroaryl, and each aryl or heteroaryl is optionally substituted with one or more —R 10 .

10. The compound of claim 1 , wherein each R 10 is independently selected from halogen and —OC 1 -C 6 alkyl.

11. The compound of claim 1 , wherein each R 10 is independently selected from F and —OCH 3 .

12. The compound of claim 1 , selected from the group consisting of:

13. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

14. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 14 , wherein the compound is:

16. The compound of claim 14 , wherein the compound is:

17. The compound of claim 14 , wherein the compound is:

18. The compound of claim 14 , wherein the compound is:

19. A pharmaceutical composition comprising the compound of claim 14 , or a pharmaceutically acceptable salt thereof.

Assignees

• Forma Therapeutics Inc

Inventors

• Schiller Shawn E R
• Herbertz Torsten
• Li Hongbin
• Graves Bradford
• Mischke Steven
• WEST Angela
• Downing Jennifer R
• Ericsson Anna

Classifications

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title