Arginine methyltransferase inhibitors and uses thereof

• US 9,765,035 B2
• Filed: 03/14/2014
• Issued: 09/19/2017
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Epizyme, Inc. (Ipsen Sa)
• Original Assignee: Epizyme, Inc. (Ipsen Sa)
• Inventors: Chesworth, Richard, Mitchell, Lorna Helen, Shapiro, Gideon, Kuntz, Kevin Wayne
• Primary Examiner(s): SAEED, KAMAL A
• Application Number:
  US14/775,246
• Publication Number:
  US 20160024017A1
• Time in Patent Office: 1,285 Days
• Field of Search: None
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 231/56 Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links

Abstract

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

Claims

1. A compound of Formula (I):

2. The compound of claim 1, wherein at least one R₁ is —

Z—

R₄, and m is 1 or 2.

3. The compound of claim 2, wherein the compound is of Formula (II):

4. The compound of claim 2, wherein R₄ is optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted C_1-6 alkyl-Cy.

5. The compound of claim 2, wherein the compound is of Formula (II-a1):

6. The compound of claim 2, wherein R₄ is selected from the group consisting of:

7. The compound of claim 1, wherein X is NR₂ and Y is N.

8. The compound of claim 1, wherein X is N and Y is NR₂.

9. The compound of claim 1, wherein the compound is selected from the group consisting of:

10. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.

11. A kit or packaged pharmaceutical comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and instructions for use thereof.

12. The compound of claim 1, wherein R_x is methyl, ethyl, isopropyl, propyl, butyl, hydroxyethyl, methoxyethyl, cyclopropyl, or cyclobutyl.

13. The compound of claim 1, wherein R₃ is hydrogen, methyl, ethyl, propyl, butyl, cyclopropyl, or cyclobutyl.

14. A pharmaceutical composition comprising a compound of claim 9, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.