Five-membered heterocycles useful as serine protease inhibitors

C - Chemistry – Metallurgy – 07 – D

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Details

C07D 235/00 (2006.01) A61K 31/00 (2006.01) A61K 31/4164 (2006.01) A61P 7/02 (2006.01)

Patent

CA 2570472

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): (I) [INSERTCHEMICAL STRUCTURE HERE] (V)[INSERT CHEMICAL STRUCTURE HERE] or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, R4, R6, R11, X1, X2, and X3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

L'invention concerne une méthode de traitement d'un trouble thrombotique ou inflammatoire qui consiste à administrer au patient une dose thérapeutiquement efficace d'au moins un composé représenté par la formule (I) ou la formule (V), ou un stéréo-isomère, ou un sel ou une forme solvatée pharmaceutiquement acceptable de celui-ci, les variables A, L, Z, R3, R4, R6, R11, X1, X2, et X3 étant tels que définis dans le descriptif. Les composés de la formule (I) sont utilisés comme inhibiteurs sélectifs de la protéase sérine de la cascade de coagulation et/ou du système d'activation par contact; notamment la thrombine, le facteur Xa, le facteur XIa, le facteur IXa, le facteur VIIa et/ou la kallicréine du plasma. En particulier, l'invention concerne des composés qui sont des inhibiteurs sélectifs du facteur XIa. Par ailleurs, l'invention concerne des composés de formule (I) ainsi que des compositions pharmaceutiques qui renferment ces composés.

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