Small molecule inhibition of transcription factor SALL4 and uses thereof

Patent metadata

Field	Value
Publication number	US-11999729-B2
Application number	US-202217978591-A
Country	US
Kind code	B2
Filing date	Nov 1, 2022
Priority date	Oct 4, 2017
Publication date	Jun 4, 2024
Grant date	Jun 4, 2024

Abstract

Provided herein are compounds that interrupt the function of SALL4. Also described are pharmaceutical compositions and medical uses of these compounds.

First claim

The invention claimed is:

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

wherein
Z is N;
R 1 is optionally substituted C 5 or C 6 -cycloalkyl, optionally substituted heterocyclyl, naphthalenyl substituted with one or more groups selected from hydroxyl and nitro,

optionally substituted oxazolyl, optionally substituted benzoisoxazolyl, optionally substituted indazolyl, optionally substituted azaindolyl, optionally substituted benzothiazolyl, optionally substituted thiazolyl, or optionally substituted carbazolyl; and
R 2 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl.

2. The compound of claim 1 , wherein R 1 is naphthalenyl substituted with one or more groups selected from hydroxyl and nitro.

3. The compound of claim 2 , wherein R 1 is selected from

4. The compound of claim 1 , wherein R 1 is selected from

5. The compound of claim 1 , wherein R 1 is optionally substituted C 5 or C 6 -cycloalkyl or optionally substituted heterocyclyl.

6. The compound of claim 5 , wherein R 1 is selected from

7. The compound of claim 1 , wherein R 1 is optionally substituted oxazolyl, optionally substituted benzoisoxazolyl, optionally substituted indazolyl, optionally substituted azaindolyl, optionally substituted benzothiazolyl, optionally substituted thiazolyl, and optionally substituted carbazolyl.

8. The compound of claim 7 , wherein R 1 is substituted with one or more groups selected from halo, oxy, nitro, sulfonate, and optionally substituted alkyl.

9. The compound of claim 8 , wherein R 1 is selected from

10. The compound of claim 1 , wherein R 2 is optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aryl.

11. The compound of claim 10 , wherein the alkyl is substituted with alkoxy, amino or optionally substituted aryl.

12. The compound of claim 10 , wherein R 2 is selected from

13. The compound of claim 10 , wherein R 2 is optionally substituted phenyl.

14. The compound of claim 13 , wherein the phenyl is substituted with one more groups selected from halo, hydroxyl, cyano, optionally substituted alkyl, optionally substituted alkoxy, carboxy, and ester.

15. The compound of claim 14 , wherein R 2 is selected from

16. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier.

17. A method of treating cancer, wherein the cancer is acute myeloid leukemia, liver cancer, lung cancer, or myelodysplastic syndromes (MDS) comprising administering to a subject the compound or pharmaceutically acceptable salt thereof of claim 1 .

18. A compound which is

or a pharmaceutically acceptable salt thereof.

19. The method of claim 17 , wherein the cancer is acute myeloid leukemia.

20. The method of claim 17 , wherein the cancer is liver cancer.

21. The method of claim 17 , wherein the cancer is lung cancer.

22. The method of claim 17 , wherein the cancer is myelodysplastic syndrome (MDS).

Assignees

• Dana Farber Cancer Inst Inc
• Brigham & Womens Hospital Inc

Inventors

• Qi Jun
• Varca Anthony
• Chai Li

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D487/04

  Ortho-condensed systems · 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

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title