Pyridyl and pyrimidinyl derivatives as histone deacetylase...

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 213/75 (2006.01) A61K 31/4418 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2692153

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

La présente invention porte sur une nouvelle classe de dérivés pyridylés et pyrimidinylés. Les composés pyridylés et pyrimidylés peuvent être utilisés pour traiter le cancer. Les composés pyridylés et pyrimidinylés peuvent également inhiber l'histone désacétylase et conviennent pour une utilisation dans l'induction sélective d'une différenciation terminale, et l'arrêt de 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 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 des maladies auto-immunes, allergiques et inflammatoires, et dans la prévention et/ou le traitement de maladies du système nerveux central (SNC), telles que les maladies neurodégénératives. La présente invention concerne en outre des compositions pharmaceutiques comprenant les dérivés pyridylés et pyrimidinylés et des régimes d'administration de doses sans danger de ces compositions pharmaceutiques, qui sont faciles à suivre, et qui conduisent à une quantité thérapeutiquement efficace des dérivés pyridylés et pyrimidinylés in vivo.

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