Piperidinyl-and piperazinyl-sulfonylmethyl hydroxamic acids...

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 407/12 (2006.01) A61K 31/44 (2006.01) C07D 211/16 (2006.01) C07D 211/22 (2006.01) C07D 401/12 (2006.01)

Patent

CA 2543715

This invention is directed generally to proteinase (also known as ~protease~) inhibitors, and, more particularly, to piperidinyl- and piperazinyl- sulfonylmethyl hydroxamic acids that, inter alia, inhibit matrix metalloproteinase (also known as ~matrix metalloprotease~ or ~MMP~) activity and/or aggrecanase activity. Such hydroxamic acids generally correspond in structure to formula (I); (wherein A1, A2, Y, E1, E2, E3, and Rx are as defined in this specification), and further include salts of such compounds. This invention also is directed to compositions of such hydroxamic acids, intermediates for the syntheses of such hydroxamic acids, methods for making such hydroxamic acids, and methods for treating conditions (particularly pathological conditions) associated with MMP activity and/or aggrecanase activity.

L'invention concerne globalement des inhibiteurs de protéinase (également connue sous le nom de <= protéase >=) et, plus précisément, des acides hydroxamiques de pipéridinyl- et de pipérazinyl-sulfonylméthyle qui, notamment, inhibent l'activité de l'aggrecanase et/ou l'activité de la métalloprotéinase matricielle (également connue sous le nom de <= métalloprotéase matricielle >= ou <= MMP >=). Ces acides hydroxamiques correspondent globalement en structure à la formule générale (I) (dans laquelle A?1¿, A?2¿, Y, E?1¿, E?2¿, E?3¿ et R?x¿ sont définis dans la présente description), et comprennent également des sels de ces composés. La présente invention concerne également des compositions obtenues à partir de ces acides hydroxamiques, des produits intermédiaires destinés à la synthèse de ces acides hydroxamiques, des méthodes destinées à la fabrication de ces acides hydroxamiques, ainsi que des méthodes destinées au traitement de troubles (et plus particulièrement de troubles pathologiques) associés à l'activité de la MMP et/ou à l'activité de l'aggrecanase.

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