Benzothiophene hydroxamic acid derivatives

Details Benzothiophene hydroxamic acid derivatives Benzothiophene hydroxamic acid derivatives

C - Chemistry, Metallurgy

07

D

C07D 333/56 (2006.01) A61K 31/38 (2006.01) A61K 31/41 (2006.01) C07D 271/10 (2006.01)

Patent

CA 2603986

The present invention relates to a novel class of hydroxamic acid derivatives. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid 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 are also 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.

L'invention concerne une nouvelle classe de dérivés d'acide hydroxamique. Ces composés d'acide hydroxamique peuvent servir au traitement des cancers. Ils peuvent en outre bloquer l'histone désacétylase et peuvent servir à induire sélectivement la différenciation terminale, et le blocage de la croissance cellulaire et/ou l'apoptose des cellules néoplasique, de manière à inhiber ainsi la prolifération de ces cellules. Les composés décrits conviennent par conséquent pour le traitement d'un patient présentant une tumeur caractérisée par une prolifération de cellules néoplasiques. Les composés décrits conviennent également pour la prévention et le traitement des maladies dans lesquelles la TRX joue un rôle, telles que les maladies auto-immunes, allergiques et inflammatoires, et pour la prévention et/ou le traitement des maladies du système nerveux central (SNC), telles que les maladies neurodégénératives. L'invention concerne en outre des compositions pharmaceutiques comprenant ces dérivés d'acide hydroxamique, et des régimes posologiques sûrs de ces compositions pharmaceutiques, qui sont faciles à respecter et qui permettent l'administration d'une dose thérapeutiquement efficace de dérivés d'acide hydroxamique in vivo.

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