Activators of class I histone deacetlyases (HDACS) and uses thereof

• US 9,115,053 B2
• Filed: 07/20/2012
• Issued: 08/25/2015
• Est. Priority Date: 07/22/2011
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Tsai, Li-Huei, Pan, Ling, Haggarty, Stephen J., Patnaik, Debasis
• Primary Examiner(s): Jackson, Shawquia
• Application Number:
  US13/554,670
• Publication Number:
  US 20130096129A1
• Time in Patent Office: 1,131 Days
• Field of Search: 544/184
• US Class Current: 1/1
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07C 217/58 with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• CPC Class Codes: C07C 219/28 having amino groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07D 307/40 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• 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 411/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders. In one aspect, the methods include administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of DAC-001, DAC-002, DAC-003, DAC-009, or DAC-012, or a compound of Formula (A), (B), (C), or (D).

Claims

1. A compound of Formula (C-VII):

2. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.

3. The compound of claim 1, wherein the compound is of the formula:

4. The compound of claim 1, wherein the compound is of the formula:

5. The compound of claim 1, wherein at least one R^C1 is C_1-6 alkyl.

6. The compound of claim 1, wherein at least one R^C1 is methyl.

7. The compound of claim 1, wherein q is 0.

8. The compound of claim 1, wherein q is 1.

9. The compound of claim 1, wherein at least one R^C2 is halogen.

10. The compound of claim 1, wherein at least one R^C2 is —

OR^C2a.

11. The compound of claim 10, wherein R^C2a is hydrogen.

12. The compound of claim 1, wherein v is 1.