947753-95-9Relevant academic research and scientific papers
Inhibitors of Histone Deacetylase
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Page/Page column 29, (2009/04/24)
The present invention relates to a novel class of compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of 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. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and sale dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.
Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1)
Wilson, Kevin J.,Witter, David J.,Grimm, Jonathan B.,Siliphaivanh, Phieng,Otte, Karin M.,Kral, Astrid M.,Fleming, Judith C.,Harsch, Andreas,Hamill, Julie E.,Cruz, Jonathan C.,Chenard, Melissa,Szewczak, Alexander A.,Middleton, Richard E.,Hughes, Bethany L.,Dahlberg, William K.,Secrist, J. Paul,Miller, Thomas A.
, p. 1859 - 1863 (2008/12/21)
An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (>100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and improved physical properties. Dose-dependent efficacy in a mouse HCT116 xenograft model was demonstrated with a phenylglycine SHI-1 analog.
