Heidebrecht, Richard W.,Close, Joshua,Kattar, Solomon D.,Tempest, Paul,Mampreian, Dawn M.,Kliman, Laura T.,Miller, Thomas,Sloman, David L.,Zabierek, Anna A.,Berk, Scott C.,Stanton, Matthew G.,Hamblett
申请号:
AU2006318773
公开号:
AU2006318773B2
申请日:
2006.11.17
申请国别(地区):
AU
年份:
2012
代理人:
摘要:
The present invention relates to a novel class of substituted spirocyclic compounds,represented by the following structural Formula: I Wherein A, B and D are independentlyselected from CR, NR, C(O) and O; E is selectedfrom a bond, CR. NR, C(O) and O; wherein atleast one of A, B, D or E is CR; and provided that when A isO, then E is not O; G is CR; R is selected from NHand OH; These compounds can inhibit histone deacetylase and are suitable foruse in selectively inducing termin differentiation, and arresting cell growthand/or apoptosis of neoplastic cells, thereby inhibiting proliferation ofsuch cells. Thus, the compounds of the present invention are useful in treatinga patient having a tumor characterized by proliferation of neoplastic cells.The compounds of the invention may also be useful in the prevention and treatmentof 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 providespharmaceutical compositions comprising the compounds of the instant inventionand safe dosing regimens of these pharmaceutical compositions, which are easyto follow, and which result in a therapeutically effective amount of these compoundsin vivo.