Thiocarbamate inhibitors of alpha-4 integrins

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 295/20 (2006.01) A61K 31/5375 (2006.01) C07D 217/14 (2006.01) C07D 491/08 (2006.01)

Patent

CA 2525934

The invention provides novel thiocarbamate alpha-4 inhibitors of the general formula (I) wherein L is -C(S)-O- or -C(O)-S-; that are resistant to metabolism having improved half-life and/or clearance properties compared to corresponding carbamate compounds wherein substituents L, X, Y, Z, R1-R4, m, n, o and p are as defined herein. Also provided are compositions comprising compounds of formula I and a carrier, diluent or excipient as well as methods of treating a disease or condition mediated by the binding interaction of alpha-4 integrins to its ligands such as inflammatory diseases.

L'invention concerne de nouveaux inhibiteurs de type thiocarbamates d'intégrines alpha-4 de formule générale (I) résistants au métabolisme, présentant des propriétés de demi-vie et/ou de clairance améliorées comparé à des composés carbamates correspondants. Dans ladite formule, les substituants L, X, Y, Z, R?1¿-R?4¿, m, n, o et p sont tels que définis dans la description. L'invention concerne également des compositions comprenant des composés de formule (I) et un support, un diluant ou un excipient, ainsi que des méthodes de traitement de maladies ou d'états liés à l'interaction de liaison des intégrines alpha-4 à leurs ligands, telles que les maladies inflammatoires.

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