Histone deacetylase and tubulin deacetylase inhibitors

Details Histone deacetylase and tubulin deacetylase inhibitors Histone deacetylase and tubulin deacetylase inhibitors

C - Chemistry, Metallurgy

07

D

C07D 413/12 (2006.01) A61K 31/357 (2006.01) A61K 31/422 (2006.01) A61K 31/427 (2006.01) A61K 31/4433 (2006.01) A61K 31/69 (2006.01) C07D 319/06 (2006.01) C07D 405/12 (2006.01) C07D 417/12 (2006.01)

Patent

CA 2654540

In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel inhibitors of histone deacetylases, tubulin deacetylases, and/or aggresome inhibitors, and pharmaceutically acceptable salts and derivatives thereof. The inventive compounds fall into two classes ~ "isorubacin" class and "isoisotubacin" class- ~ all of which include a 1,3-dioxane core. The present invention further provides methods for treating disorders regulated by histone deacetylase activity, tubulin deacetylase activity, and/or the aggresome (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, protein degradation disorders, protein deposition disorders, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.

Au vu de la nécessité de développer de nouveaux agents thérapeutiques et des procédés efficaces de synthèse de ceux-ci, l'invention concerne de nouveaux inhibiteurs d'histone désacétylases, de tubuline désacétylases et/ou des inhibiteurs d'aggrésomes, et des sels pharmaceutiquement acceptables et des dérivés de ces composés. Les composés selon l'invention sont regroupés en deux classes; la classe des "isorubacines" et la classe des "isoisotubacines", toutes deux ayant un noyau 1,3-dioxane. L'invention concerne également des procédés de traitement de troubles régulés par une activité d'histone désacétylase, une activité de tubuline désacétylase et/ou par l'aggrésome (par ex, maladies prolifératives, cancers, maladies inflammatoires, infections causées par des protozoaires, troubles de dégradations protéiques, troubles de dépôts protéiques, etc.), consistant à administrer une quantité thérapeutique d'un composé selon l'invention à un sujet nécessitant un tel traitement. L'invention concerne également des procédés de préparation des composés selon l'invention.

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