Arginine methyltransferase inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-10081603-B2
Application number	US-201715421699-A
Country	US
Kind code	B2
Filing date	Feb 1, 2017
Priority date	Mar 14, 2013
Publication date	Sep 25, 2018
Grant date	Sep 25, 2018

Abstract

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

First claim

What is claimed is:

1. A method of inhibiting an arginine methyl transferase (RMT) comprising contacting a cell with an effective amount of a compound of formula:

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the arginine methyl transferase is PRMT1.

3. The method of claim 1 , wherein the arginine methyl transferase is PRMT6.

4. A method of modulating gene expression comprising contacting a cell with an effective amount of a compound of formula:

or a pharmaceutically acceptable salt thereof.

5. A method of modulating transcription comprising contacting a cell with an effective amount of a compound of formula:

or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein the cell is in vitro.

7. The method of claim 1 , wherein the cell is in a subject.

8. A method of therapeutic treatment of a RMT-mediated disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula:

or a pharmaceutically acceptable salt thereof.

9. The method of claim 8 , wherein the RMT-mediated disorder is a PRMT1-mediated disorder.

10. The method of claim 8 , wherein the disorder is a proliferative disorder.

11. The method of claim 10 , wherein the disorder is cancer.

12. The method of claim 8 , wherein the disorder is a neurological disorder.

13. The method of claim 12 , wherein the disorder is amyotrophic lateral sclerosis.

14. The method of claim 8 , wherein the disorder is a muscular dystrophy.

15. The method of claim 8 , wherein the disorder is an autoimmune disorder.

16. The method of claim 8 , wherein the disorder is a vascular disorder.

17. The method of claim 8 , wherein the disorder is a metabolic disorder.

18. The method of claim 4 , wherein the cell is in vitro.

19. The method of claim 4 , wherein the cell is in a subject.

20. The method of claim 5 , wherein the cell is in vitro.

21. The method of claim 5 , wherein the cell is in a subject.

22. The method of claim 11 , wherein the cancer is breast cancer, prostate cancer, lung cancer, colorectal cancer, bladder cancer, kidney cancer, melanoma, leukemia, or lymphoma.

23. The method of claim 22 , wherein the leukemia is acute myelocytic leukemia.

24. The method of claim 22 , wherein the lymphoma is non-Hodgkin lymphoma.

25. The method of claim 8 , wherein the compound is:

26. The method of claim 8 , wherein the compound is a pharmaceutically acceptable salt of:

27. The method of claim 8 , wherein the subject is a human.

Assignees

• Epizyme Inc
• Epizyme Inc

Inventors

• Chesworth Richard
• Mitchell Lorna Helen
• Shapiro Gideon
• Swinger Kerren Kalai

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title