Uses of diazepane derivatives

Patent metadata

Field	Value
Publication number	US-10793571-B2
Application number	US-201515115085-A
Country	US
Kind code	B2
Filing date	Feb 2, 2015
Priority date	Jan 31, 2014
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.

First claim

What is claimed is:

1. A method of treating a leukemia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the leukemia is biphenotypic B myelomonocytic leukemia, acute monocytic leukemia, erythroleukemia, acute myeloid leukemia, chronic lymphocytic leukemia, or mixed-lineage leukemia (MLL).

3. The method of claim 1 , wherein the subject is a human.

4. The method of claim 2 , wherein the subject is a human.

5. The method of claim 1 , wherein the leukemia is acute lymphocytic leukemia, chronic myelocytic leukemia, hairy cell leukemia, precursor T-lymphoblastic leukemia, or chronic neutrophilic leukemia.

6. The method of claim 5 , wherein the subject is a human.

7. The method of claim 1 , wherein the leukemia is acute myeloid leukemia, acute monocytic leukemia, or erythroleukemia.

8. The method of claim 1 , wherein the leukemia is acute myeloid leukemia and the subject is a human.

9. The method of claim 1 , wherein the leukemia is acute monocytic leukemia and the subject is a human.

10. The method of claim 1 , wherein the leukemia is erythroleukemia and the subject is a human.

11. A method of treating a leukemia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof.

12. The method of claim 11 , wherein the subject is a human.

13. The method of claim 11 , wherein the leukemia is biphenotypic B myelomonocytic leukemia, acute monocytic leukemia, erythroleukemia, acute myeloid leukemia, chronic lymphocytic leukemia, or mixed-lineage leukemia (MLL).

14. The method of claim 13 , wherein the subject is a human.

15. The method of claim 11 , wherein the leukemia is acute lymphocytic leukemia, chronic myelocytic leukemia, hairy cell leukemia, precursor T-lymphoblastic leukemia, or chronic neutrophilic leukemia.

16. The method of claim 15 , wherein the subject is a human.

17. The method of claim 11 , wherein the leukemia is acute myeloid leukemia, acute monocytic leukemia, or erythroleukemia.

18. The method of claim 11 , wherein the leukemia is acute myeloid leukemia and the subject is a human.

19. The method of claim 11 , wherein the leukemia is acute monocytic leukemia and the subject is a human.

20. The method of claim 11 , wherein the leukemia is erythroleukemia and the subject is a human.

Assignees

• Dana Farber Cancer Inst Inc

Inventors

• Bradner James E
• Gray Nathanael S
• Qi Jun
• Mckeown Michael R
• Buckley Dennis

Classifications

• A61K31/5517

  condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam · CPC title

• A61K31/551

  having two nitrogen atoms, e.g. dilazep · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/5513

  1,4-Benzodiazepines, e.g. diazepam {or clozapine} · CPC title