Inhibitors of histone deacetylase

• US 8,030,344 B2
• Filed: 03/06/2008
• Issued: 10/04/2011
• Est. Priority Date: 03/13/2007
• Status: Active Grant

• Current Assignee: 92229129 Quebec Inc.
• Original Assignee: MethylGene, Inc.
• Inventors: Vaisburg, Arkadii, Frechette, Sylvie, Paquin, Isabelle, Moradei, Oscar, Isakovic, Lubo, Roy, Simon
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US12/043,450
• Publication Number:
  US 20080227826A1
• Time in Patent Office: 1,307 Days
• Field of Search: 514/428, 548/566
• US Class Current: 514/428
• 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: C07D 207/14 Nitrogen atoms not forming part of a nitro radical
• 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 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links

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. One aspect of the invention provides compounds of formula (1):

in which T, A and X are as described herein.

Claims

1. A compound of formula (1):

2. The compound according to claim 1, wherein T is NH₂.

3. The compound according to claim 1, wherein A is unsubstituted or optionally-substituted phenyl.

4. The compound according to claim 1, wherein A is a 6-membered ring and the X—

and carbonyl moieties are arranged in a 1,4-manner relative to one another on the ring.

5. The compound according to claim 1, wherein A is unsubstituted arylene.

6. The compound according to claim 1, wherein A is unsubstituted phenylene.

7. The compound according to claim 1, wherein X is

8. The compound according to claim 1, wherein X is

9. The compound claim 1, wherein X is

10. The compound according to claim 1, wherein X is

11. The compound according to claim 1, wherein X is

12. A composition comprising a compound according to claim 1 present in at least about 30% enantiomeric or diastereomeric excess.

13. The composition according to claim 12 wherein the compound is present in at least about 50% enantiomeric or diastereomeric excess.

14. The composition according to claim 12 wherein the compound is present in at least 80% enantiomeric or diastereomeric excess.

15. The composition according to claim 12 wherein the compound is present in at least 90% enantiomeric or diastereomeric excess.

16. A composition comprising a compound according to claim 1 present as a substantially racemic mixture.

17. A pharmaceutical composition comprising a compound according to claim 1, and a pharmaceutically acceptable, diluent, carrier or excipient.