Covalent inhibitors of creatine kinase (CK) and uses thereof for treating and preventing cancer

Patent metadata

Field	Value
Publication number	US-12570620-B2
Application number	US-202118033269-A
Country	US
Kind code	B2
Filing date	Oct 22, 2021
Priority date	Oct 23, 2020
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

Abstract

The present disclosure relates to compounds that are capable of inhibiting creatine kinase. The present disclosure also relates to methods of treating cancer, such as hematological malignancies.

First claim

We claim:

1 . A compound of Formula IV or V:

or a pharmaceutically acceptable salt thereof, wherein
R 4 is alkyl, alkenyl, alkynyl, halo, hydroxyl, carboxyl, acyl, acetyl, ester, thioester, alkoxy, phosphoryl, amino, amide, cyano, nitro, azido, alkylthio, cycloalkyl, cycloalkylalkyl, heterocyclylalkyl, heteroaralkyl, sulfonamide, aryl, heteroaryl, heterocyclyl, or aralkyl;
R 5A and R 5B are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, hydroxyl, carboxyl, acyl, acetyl, ester, thioester, cycloalkyl, cycloalkylalkyl, heterocyclylalkyl, heteroaralkyl, aryl, heteroaryl, heterocyclyl, and aralkyl;
n=0-4; such that when n=0, then:
a) one of R 5A and R 5B in Formula IV are selected from alkyl, alkenyl, alkynyl, hydroxyl, carboxyl, acyl, acetyl, ester, thioester, cycloalkyl, cycloalkylalkyl, heterocyclylalkyl, heteroaralkyl, aryl, heteroaryl, heterocyclyl, and aralkyl; and
b) R 5A and R 5B in Formula V are independently selected from alkyl, alkenyl, alkynyl, hydroxyl, carboxyl, acyl, acetyl, ester, thioester, cycloalkyl, cycloalkylalkyl, heterocyclylalkyl, heteroaralkyl, aryl, heteroaryl, heterocyclyl, and aralkyl.

2 . A compound of claim 1 , where n=0-1.

3 . A compound of claim 2 , where R 4 is selected from alkyl, halo, ester, and sulfonamide.

4 . A compound of claim 3 , where R 5A is hydrogen and R 5B is alkyl.

5 . A compound of claim 1 , where the compound is of Formula IV.

6 . A compound of claim 1 , where the compound is of Formula V.

7 . A compound of claim 6 , where n=0-1.

8 . A compound of claim 7 , where R 4 is selected from alkyl, halo, ester, and sulfonamide.

9 . A compound of claim 8 , where R 5A is hydrogen and R 5B is hydrogen or alkyl.

10 . A compound of claim 1 , where the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

11 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutical excipient.

12 . A method of treating cancer in a subject in need therefore, comprising administering a compound of claim 1 or a pharmaceutically acceptable salt thereof to the subject.

Assignees

• Dana Farber Cancer Inst Inc

Inventors

• Gray Nathanael S
• Chouchani Edward
• Zhang Tinghu
• Darabedian Narek
• Ji Wenzhi
• Che Jianwei

Classifications

• C07F9/65335

  condensed with carbocyclic rings or carbocyclic ring systems · CPC title

• C07D498/04

  Ortho-condensed systems · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D413/04

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