Compounds for proteasome enzyme inhibition

Details Compounds for proteasome enzyme inhibition Compounds for proteasome enzyme inhibition

C - Chemistry, Metallurgy

07

K

C07K 5/087 (2006.01) A61K 38/06 (2006.01) C07K 5/08 (2006.01)

Patent

CA 2562411

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

L'invention concerne des composés à base de peptides qui comprennent des anneaux à trois éléments contenant des hétéroatomes et qui permettent d'inhiber efficacement et sélectivement des activités spécifiques d'hydrolases à N-terminal nucléophile (Ntn). Les activités de ces Ntn possédant plusieurs activités peuvent être inhibées de manière différentielle par les composés susmentionnés. Par exemple, l'activité similaire à la chymotrypsine du protéasome 20S peut être sélectivement inhibée au moyen des composés de cette invention. Ces composés à base de peptides renferment au moins trois unités de peptide, un époxyde ou une aziridine et une fonctionnalisation au niveau du terminal N. Parmi d'autres utilisations thérapeutiques, les composés à base de peptides sont escomptés afficher des propriétés anti-inflammatoires et inhiber la prolifération cellulaire.

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