Soft protease inhibitors and pro-soft forms thereof

C - Chemistry – Metallurgy – 07 – F

Patent

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Details

C07F 5/02 (2006.01) A61K 31/69 (2006.01) A61K 38/05 (2006.01) C07K 5/06 (2006.01) C12N 9/50 (2006.01)

Patent

CA 2633803

The invention provides compounds and methods for inhibiting proteases. One aspect of the invention features prosoft inhibitors which react with an activating protease to release an active inhibitor moiety in proximity to a target protease. In certain instances, compounds inhibit proteasomes and/or post-proline cleaving enzymes (PPCE), such as dipeptidyl peptidase IV. The compounds of the invention provide a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

La présente invention concerne des composés et des procédés permettant l'inhibition de protéases. Selon un aspect de l'invention, des pro-inhibiteurs légers réagissent avec une protéase activatrice pour libérer une fraction active d'inhibiteur à proximité d'une protéase cible. Dans certains cas, les composés inhibent les protéasomes et/ou les enzymes de clivage post-proline (PPCE), telles que la dipeptidyl-peptidase IV. Les composés de l'invention permettent d'obtenir un meilleur indice thérapeutique, dû en partie à une toxicité réduite et/ou à une spécificité améliorée vis-à-vis de la protéase ciblée.

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