MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF

• US 20130310379A1
• Filed: 11/21/2011
• Published: 11/21/2013
• Est. Priority Date: 11/19/2010
• Status: Abandoned Application

• Current Assignee: Constellation Pharmaceuticals Incorporated (Morphosys Ag)
• Original Assignee: Constellation Pharmaceuticals Incorporated (Morphosys Ag)
• Inventors: Albrecht, Brian K., Audia, James Edmund, Harmange, Jean-Christophe, Naveschuk, Christopher G., Gagnon, Alexandre
• Application Number:
  US13/988,180
• Publication Number:
  US 20130310379A1
• Time in Patent Office: Days
• US Class Current: 514/235.5
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: C07D 207/14 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 211/58 attached in position 4
• 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
• CPC Class Codes: C07D 451/04 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

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

Claims

1. A method of inhibiting EZH2 activity comprising administering a compound of formula I:

2-24. -24. (canceled)

25. A compound of formula II:

26. The compound of claim 25, wherein R¹, R^1′

, R² and R^2′

are methyl.

27. The compound of claim 26, wherein R³, R^3′

, R⁴, R^4′

, R⁵ and R′

are hydrogen.

28. The compound of claim 26, wherein L¹ is selected from —

OCH₂—

, —

CH₂O—

, —

OC(O)—

, —

N(R′

)C(O)—

, —

C(O)N(R′

)—

, and optionally substituted ethenylene.

31. The compound of claim 28, wherein L¹ is —

NH—

C(O)—

, —

OCH₂—

, —

CH₂O—

, —

OC(O)—

, and —

CH═

CH—

.

32. The compound of claim 25, wherein Ring B is optionally substituted phenyl or optionally substituted pyridinyl.

37. The compound of claim 32, wherein L² is selected from —

CH₂O—

, —

O—

, and —

CH(CH₃)O.

38. The compound of claim 25, wherein Ring C is optionally substituted phenyl.

41. The compound of claim 25, wherein Ring C is optionally substituted pyridinyl, pyrimidinyl or pyrazinyl.

42. The compound of claim 41, wherein Ring C is selected from

44. The compound of claim 25, wherein Ring C is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

46. The compound of claim 25, wherein Ring C is selected from pyrrolidinyl, furanyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, piperidinyl, piperazinyl and morpholinyl.

48. The compound of claim 25, wherein Ring C is optionally substituted indolyl, quinolinyl, isoquinolinyl or naphthyl.

50. A pharmaceutical composition comprising a compound of claim 25 and a pharmaceutically acceptable excipient.

57. The compound of claim 25, selected from any one of the compounds set forth below:

29-30. -30. (canceled)

33-36. -36. (canceled)

39-40. -40. (canceled)

43. (canceled)

45. (canceled)

47. (canceled)

49. (canceled)

51-56. -56. (canceled)