MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF

• US 20150315148A1
• Filed: 05/08/2015
• Published: 11/05/2015
• Est. Priority Date: 11/18/2011
• Status: Active Grant

• Current Assignee: Constellation Pharmaceuticals Incorporated (Morphosys Ag)
• Original Assignee: Constellation Pharmaceuticals Incorporated (Morphosys Ag)
• Inventors: Albrecht, Brian K., Gagnon, Alexandre, Harmange, Jean-Christophe, Nasveschuk, Christopher G., Audia, James Edmund
• Granted Patent: US 9,409,865 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 213/81 Amides; Imides
• 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

Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.

Claims

1. A compound having structural Formula I:

2. The compound of claim 1, wherein Z is ═

CH—

.

3. The compound of claim 1, wherein each R¹ is independently selected from hydrogen and —

CH₃.

4. The compound of claim 3, wherein each R¹ is —

CH₃.

5. The compound of claim 1, wherein one R¹ is —

CH₃; and

the other R¹ is selected from —

OCH₃ and —

NHCH₃.

7. The compound of claim 1, wherein each R³ is independently selected from hydrogen, halo, C₁-C₄ alkyl and —

O-phenyl.

8. The compound of claim 7, wherein each R³ is independently selected from hydrogen, chloro, —

CH₃ and —

O-phenyl.

10. The compound of claim 1, wherein —

R⁵—

H is selected from —

CH₃, —

CH(CH₃)₂, —

(CH₂)₂CH₃, —

CH₂CH₃, —

OCH₂CH₃, —

OCH(CH₃)₂, —

OCH₃, and —

OCH₂CH(CH₃)₂.

12. The compound of claim 1, wherein R⁶ is hydrogen.

13. The compound of claim 1 having structural formula I-i:

14. The compound of claim 1 having structural formula I-i:

16. A pharmaceutically acceptable composition comprising:

a) the compound of claim 1

or a pharmaceutically acceptable salt thereof

and

b) a pharmaceutically acceptable carrier.

18. The compound of claim 1, wherein the compound is

19. A method of treating a subject suffering from a disease and/or disorder associated with cellular proliferation, comprising the step of administering to the subject a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

20. The method of claim 19, wherein the disease is cancer.

21. The method of claim 20, wherein the cancer is selected from breast cancer, prostate cancer, colon cancer, renal cell carcinoma, glioblastoma multiforme cancer, bladder cancer, melanoma, bronchial cancer, lymphoma and liver cancer.

6. (canceled)

9. (canceled)

11. (canceled)

15. (canceled)

17. (canceled)