Hydroxamic acid compounds and methods of use thereof

Details Hydroxamic acid compounds and methods of use thereof Hydroxamic acid compounds and methods of use thereof

C - Chemistry, Metallurgy

07

D

C07D 211/02 (2006.01) A61K 31/4427 (2006.01) A61K 31/444 (2006.01) A61K 31/47 (2006.01) A61K 31/4725 (2006.01) C07D 213/72 (2006.01) C07D 213/79 (2006.01)

Patent

CA 2520611

The present invention relates to a novel class of hydroxamic acid derivatives having at least two aryl containing groups, at least one of which is a quinolinyl, isoquinolinyl or benzyl moiety, linked to the hydroxamic acid group through a methylene chain. The hydroxamic acid compounds can be used to treat cancer, for example, brain 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 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.

La présente invention concerne une nouvelle classe de dérivés d'acide hydroxamique qui possèdent au moins deux groupes aryle, un de ces groupes au moins est une fraction quinolinyle, isoquinolinyle ou benzyle, liée au groupe d'acide hydroxamique via une chaîne méthylène. On peut utiliser ces composés d'acide hydroxamique pour traiter un cancer, par exemple un cancer du cerveau. Ces composés d'acide hydroxamique peuvent aussi inhiber l'histone déacétylase et conviennent pour induire sélectivement une différentiation terminale et arrêter une croissance cellulaire et/ou l'apoptose de cellules néoplasiques, inhibant ainsi la prolifération de ces cellules. Ainsi, les composés de cette invention conviennent-ils pour le traitement d'un patient atteint d'une tumeur caractérisée par la prolifération de cellules néoplasiques. Les composés de cette invention conviennent aussi pour la prévention et le traitement de maladies induites par TRX, telles que des maladies auto-immunes, allergiques et inflammatoires, et pour la prévention et/ou le traitement de maladies du système nerveux central (CNS), telles que des maladies neurodégénératives.

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