Inhibition of OLIG2 activity

• US 10,227,333 B2
• Filed: 02/10/2016
• Issued: 03/12/2019
• Est. Priority Date: 02/11/2015
• Status: Active Grant

• Current Assignee: Curtana Pharmaceuticals, Inc.
• Original Assignee: Curtana Pharmaceuticals, Inc.
• Inventors: Beaton, Graham, Tucci, Fabio, Ravula, Satheesh B., Wang, Hua-Yu
• Primary Examiner(s): Rao, Deepak R
• Application Number:
  US15/040,948
• Publication Number:
  US 20160237069A1
• Time in Patent Office: 1,126 Days
• Field of Search: 544321, 544323, 514275
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 239/48 Two nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links

Abstract

Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of Olig2. Also described herein are methods of using such Olig2 inhibitors, alone and in combination with other compounds, for treating cancer and other diseases. In particular the Olig2 inhibitors may be used to treat glioblastoma.

Claims

1. A compound having the structure of Formula (I):

2. The compound of claim 1, wherein R₂, R₃, and R₄ are each independently H, —

CN, C₁-C₄alkyl, C₃-C₆cycloalkyl, or C₂-C₇heterocycloalkyl.

3. The compound of claim 1, wherein R₂ is C₁-C₄alkyl, C₃-C₆cycloalkyl, or C₂-C₇heterocycloalkyl;

R₃ is H; and

R₄ is H.

4. The compound of claim 3, wherein R₂ is CH₃ or C₃-C₆cycloalkyl.

5. The compound of claim 1, wherein R₂ is H;

R₃ is C₁-C₄alkyl, C₃-C₆cycloalkyl, or C₂-C₇heterocycloalkyl; and

R₄ is H.

6. The compound of claim 5, wherein R₃ is CH₃.

7. The compound of claim 1, wherein R₁₃ is —

CH₃ or —

CH₂CH₃.

8. The compound of claim 1, wherein J is N.

9. The compound of claim 1, wherein R₅ is substituted or unsubstituted C₁-C₆alkyl.

10. The compound of claim 9, wherein R₅ is CH₃ or CH₂CH₃.

11. The compound of claim 1, wherein each R₁ is independently halogen, —

CN, —

NO₂, —

OH, —

CF₃, substituted or unsubstituted C₁-C₆alkyl, substituted or unsubstituted C₁-C₆alkoxy, substituted or unsubstituted C₁-C₆heteroalkyl, substituted or unsubstituted C₂-C₇heterocycloalkyl, substituted or unsubstituted C₃-C₈cycloalkyl, substituted or unsubstituted C₆-C₁₀aryl, or substituted or unsubstituted C₂-C₇heteroaryl.

12. The compound of claim 1, wherein X is C(R₇);

Y is N;

Z is N; and

R₇ is H.

14. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

15. A method for treating a disease in a subject comprising administering to the subject in need thereof a composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof;

wherein the disease is Down'"'"'s Syndrome or cancer selected from brain cancer, glioblastoma multiforme, medulloblastoma, astrocytomas, brain stem gliomas, meningiomas, oligodendrogliomas, melanoma, lung cancer, breast cancer, or leukemia.

13. A compound having a structure selected from: