Inhibitors of Histone Deacetylase

• US 20080132503A1
• Filed: 04/05/2007
• Published: 06/05/2008
• Est. Priority Date: 04/07/2006
• Status: Active Grant

• Current Assignee: 92229129 Quebec Inc.
• Original Assignee: MethylGene, Inc.
• Inventors: Mancuso, John, Roy, Simon, Besterman, Jeffrey, Tessier, Pierre, Vaisburg, Arkadii, Frechette, Sylvie, Leit, Silvana, Paquin, Isabelle, Moradei, Oscar, Mallais, Tammy, Smil, David, Machaalani, Roger, Deziel, Robert
• Granted Patent: US 8,598,168 B2
• Time in Patent Office: Days
• US Class Current: 514/235.5
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 235/56 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/40 having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 271/28 to a carbon atom of a non-condensed six-membered aromatic ring
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 207/14 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 207/325 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 213/40 Acylated substituent nitrogen atom
• CPC Class Codes: C07D 213/56 Amides
• CPC Class Codes: C07D 213/61 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 213/89 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 267/08 having the hetero atoms in positions 1 and 4
• CPC Class Codes: C07D 277/28 Radicals substituted by nitrogen atoms
• CPC Class Codes: C07D 277/36 Sulfur atoms
• CPC Class Codes: C07D 295/155 with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 317/58 Radicals substituted by nitrogen atoms nitro radicals C07D317/52
• CPC Class Codes: C07D 333/20 by nitrogen atoms nitro, nitroso radicals C07D333/12
• CPC Class Codes: C07D 333/28 : Halogen atoms
• CPC Class Codes: C07D 333/36 : Nitrogen atoms
• CPC Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/70 : attached in position 2
• 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 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 487/08 : Bridged systems

Abstract

The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

Claims

1. A compound of formula I:

60. A composition comprising a compound according to any one of claims 1-16, 46, or 49 and a pharmaceutically acceptable carrier, excipient, or diluent.

61. A method of inhibiting histone deacetylase in a cell, comprising contacting a cell in which inhibition of histone deacetylase is desired with a compound according to any one of claims 1-16, 46, or 49.

2. A compound of Formula I_A

3. A compound of Formula I_B:

4. A compound of Formula I_C:

5. A compound of Formula I_D:

6. A compound of Formula I_E:

7. A compound of Formula I_F:

8. A compound of Formula I_G:

9. A compound of Formula I_H:

10. A compound of Formula I_I:

11. A compound of Formula I_J:

12. A compound of Formula I_K:

13. A compound of Formula I_L:

14. A compound of Formula I_M:

15. A compound of Formula I_N:

16. A compound of Formula I_O:

17-45. -45. (canceled)

46. A compound having Formula (II):

47-48. -48. (canceled)

49. A compound having formula III

50-59. -59. (canceled)