Hydroxyalkylarylamide derivatives

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 333/20 (2006.01) A61K 31/381 (2006.01) A61K 31/4025 (2006.01) A61P 35/00 (2006.01) C07D 409/12 (2006.01)

Patent

CA 2635210

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

La présente invention concerne une classe atypique de dérivés d~hydroxyalkylarylamide. Les composés instantanés peuvent s~utiliser pour traiter le cancer. Ces dérivés d~arylamide fluorés peuvent aussi inhiber l~histone déacétylase et peuvent s~utiliser pour induire de manière sélective une différenciation terminale, et arrêter une croissance cellulaire et/ou une apoptose de cellules néoplastiques, et inhiber par conséquent la prolifération de telles cellules. Ainsi, les composés de la présente invention sont utiles pour le traitement d~un patient souffrant d~une tumeur caractérisée par la prolifération de cellules néoplastiques. Les composés de cette invention peuvent aussi être utiles dans la prévention et le traitement de maladies facilitées par TRX, tels que les maladies auto-immunitaires, allergiques et inflammatoires, et dans la prévention et/ou le traitement de maladies du système nerveux central (CNS), telles que des maladies neurodégénératives. La présente invention propose aussi des compositions pharmaceutiques comprenant des dérivés d'acide hydroxamique et des régimes de dose sans danger de ces compositions pharmaceutiques, qui sont faciles à suivre et qui résultent d~une quantité effective au niveau thérapeutique des dérivés d~acide hydroxamique in vivo.

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