Substituted 6,5-fused bicyclic heteroaryl compounds

• US 9,637,472 B2
• Filed: 11/07/2014
• Issued: 05/02/2017
• Est. Priority Date: 02/28/2011
• Status: Active Grant

• Current Assignee: Epizyme, Inc. (Ipsen Sa)
• Original Assignee: Epizyme, Inc. (Ipsen Sa)
• Inventors: Kuntz, Kevin Wayne, Olhava, Edward James, Chesworth, Richard, Duncan, Kenneth William
• Primary Examiner(s): RAO, SAVITHA M
• Application Number:
  US14/536,162
• Publication Number:
  US 20150065483A1
• Time in Patent Office: 907 Days
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present invention relates to substituted 6,5-fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Claims

1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

2. The compound of claim 1, wherein R₆ is phenyl substituted with one or more -Q₂-T₂;

or R₆ is 5 to 6-membered heteroaryl containing 1-3 heteroatoms selected from N, O, and S and optionally substituted with one or more -Q₂-T₂, provided that the heteroaryl is not thiophenyl;

or R₆ is halo, C₁-C₃ alkyl substituted with one or more -Q₂-T₂, C₂-C₆ alkenyl, C₄-C₆ cycloalkyl, C(O)H, OR_a, or —

C(O)R_a, in which R_a is C₁-C₆ alkyl or 4 to 7-membered heterocycloalkyl;

or R₆ is 4 to 7-membered heterocycloalkyl optionally substituted with one or more -Q₂-T₂, in which -Q₂-T₂ is oxo or Q₂ is a bond and T₂ is —

OR_c, —

NR_cR_d, —

C(O)R_c, —

C(O)OR_c, —

S(O)₂R_c, C₁-C₆ alkyl, or 4 to 7-membered heterocycloalkyl, each of which is optionally substituted with one or more -Q₃-T₃ when R_c or R_d is not H.

3. The compound of claim 1, wherein R₇ is 5 to 6-membered heterocycloalkyl optionally substituted with one or more -Q₅-T₅.

4. The compound of claim 1, wherein T₅ is H, halo, C₁-C₆ alkyl, C₁-C₆ alkoxyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, or 4 to 7-membered heterocycloalkyl;

or Q₅ is a bond and T₅ is C₁-C₆ alkyl, C₃-C₈ cycloalkyl, or 4 to 7-membered heterocycloalkyl;

or Q₅ is CO and T₅ is C₁-C₆ alkyl, C₁-C₆ alkoxyl, C₃-C₈ cycloalkyl, or 4 to 7-membered heterocycloalkyl;

or Q₅ is C₁-C₃ alkyl linker and T₅ is H or C₆-C₁₀ aryl.

5. The compound of claim 1, wherein each of R₂ and R₄, independently is H or C₁-C₆ alkyl optionally substituted with amino, mono-C₁-C₆ alkylamino, di-C₁-C₆ alkylamino, or C₆-C₁₀ aryl.

6. The compound of claim 1, wherein R₁ is H.

7. The compound of claim 1, wherein R₃ is H.

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

9. The compound of claim 2, wherein R₆ is phenyl or a 5 to 6-membered heteroaryl containing 1-3 heteroatoms selected from N, O, and S, which is substituted with one or more -Q₂-T₂.

10. The compound of claim 2, wherein R₆ is phenyl which is substituted with one or more -Q₂-T₂.

11. The compound of claim 9, wherein Q₂ is an unsubstituted C₁-C₃ alkyl linker.

12. The compound of claim 9, wherein T₂ is a 4- to 7-membered heterocycloalkyl optionally substituted with one or more -Q₃-T₃.

13. The compound of claim 1, wherein Q₂ is an unsubstituted C₁-C₃ alkyl linker.

14. The compound of claim 1, wherein T₂ is a 4- to 7-membered heterocycloalkyl optionally substituted with one or more -Q₃-T₃.

15. The compound of claim 1, wherein T₂ is —

OR_c, —

NR_cR_d, —

C(O)R_c, —

C(O)OR_c, or —

S(O)₂R_c.

16. The compound of claim 1, wherein R₂ and R₄ are methyl.

17. The compound of claim 1, wherein R₅, R₉, and R₁₀ is H.

18. A compound of claim 1 selected from:

19. A compound of claim 1 selected from: