4-carboxybenzylamino derivatives as histone deacetylase inhibitors
The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also 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 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.
1. A compound selected from:
1,1-dimethylethyl[(4-{[(4-hydroxybiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate;
4-(aminomethyl)-N-(4-hydroxybiphenyl-3-yl)benzamide;
methyl[(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate;
ethyl[(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate;
1-methylethyl[(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate;
propyl[(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate;
2-methylpropyl[(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate;
ethyl{[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}carbamate;
methyl{[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}carbamate;
1-methylethyl {[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}carbamate;
propyl{[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}carbamate; and
2-methylpropyl {[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}carbamate;
or a stereoisomer or pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to claim 1 , and a pharmaceutically acceptable carrier.
3. The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.