Phosphorus derivatives as histone deacetylase inhibitors

C - Chemistry – Metallurgy – 07 – F

Patent

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Details

C07F 9/6553 (2006.01) A61K 31/66 (2006.01) A61K 31/662 (2006.01) A61P 35/00 (2006.01) C07F 9/32 (2006.01) C07F 9/40 (2006.01) C07F 9/547 (2006.01) C07F 9/6503 (2006.01) C07F 9/6564 (2006.01) C07F 9/6574 (2006.01)

Patent

CA 2657288

The present invention relates to a novel class of phosphorus derivatives. The phosphorus compounds can be used to treat cancer. The phosphorus 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 phosphorus derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the phosphorus derivatives in vivo.

La présente invention concerne une nouvelle classe de dérivés du phosphore. Les composés du phosphore peuvent être utilisés pour traiter le cancer. Les composés du phosphore peuvent également inhiber l'histone désacétylase et sont appropriés pour être utilisés dans l'induction sélective d'une différenciation terminale et dans l'arrêt de la croissance cellulaire et/ou l'apoptose de cellules néoplasiques, inhibant de cette façon la prolifération de telles cellules. Ainsi, les composés de la présente invention sont utiles dans le traitement d'un patient ayant une tumeur caractérisée par la prolifération de cellules néoplasiques. Les composés de l'invention peuvent également être utiles dans la prévention et le traitement de maladies à médiation par TRX, telles que les maladies auto-immunes, allergiques et inflammatoires, et dans la prévention et/ou le traitement de maladies du système nerveux central (CNS), telles que les maladies neurodégénératives. La présente invention propose également des compositions pharmaceutiques comprenant les dérivés du phosphore et des régimes d'administration de doses sans danger de ces compositions pharmaceutiques, faciles à suivre et résultant en la présence in vivo d'une quantité thérapeutiquement efficace des dérivés du phosphore.

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