Histone deacetylase inhibitor prodrugs
US8227636B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Apr 5, 2005 |
| Grant date | Jul 24, 2012 |
| Priority date | — |
| Expiry date | Jun 15, 2028 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D215/42
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (TRX)-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.