Silicon derivatives as histone deacetylase inhibitors

C - Chemistry – Metallurgy – 07 – F

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C07F 7/10 (2006.01) A61K 31/695 (2006.01) A61P 35/00 (2006.01) C07F 7/08 (2006.01)

Patent

CA 2694297

The present invention relates to a novel class of Silicon derivatives. The Silicon compounds can be used to treat cancer. The Silicon compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal dif-ferentiation, 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 Silicon deriva-tives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the Silicon derivatives in vivo.

L'invention concerne une nouvelle classe de dérivés de silicium. Les composés de silicium peuvent être utilisés pour traiter le cancer. Les composés de silicium peuvent aussi inhiber l'histone désacétylase et conviennent pour une utilisation dans l'induction sélective d'une différenciation terminale, et pour arrêter la croissance cellulaire et/ou l'apoptose de cellules néoplasiques, empêchant ainsi la prolifération de telles cellules. Ainsi, les composés de la présente invention sont utiles pour traiter un patient présentant une tumeur caractérisée par une prolifération de cellules néoplasiques. Les composés de l'invention peuvent aussi être utiles dans la prévention et le traitement de maladies provoquées par la thiorédoxine (TRX), comme des maladies auto-immunes, allergiques ou inflammatoires, et pour la prévention et/ou le traitement de maladies du système nerveux central (CMS), comme des maladies neurodégénératives. La présente invention fournit en outre des compositions pharmaceutiques comprenant des dérivés de silicium et des schémas de dosage sûr de ces compositions pharmaceutiques, qui sont faciles à suivre, et qui ont pour résultat une quantité thérapeutiquement efficace des dérivés de silicium in vivo.

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