Methods for selectively inhibiting janus tyrosine kinase 3...

C - Chemistry – Metallurgy – 07 – C

Patent

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C07C 225/20 (2006.01) A61K 31/00 (2006.01) A61K 31/132 (2006.01) A61K 31/335 (2006.01) A61P 37/06 (2006.01) A61P 37/08 (2006.01) C12Q 1/00 (2006.01) C12Q 1/02 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2506432

Methods are disclosed for inhibiting or disrupting Janus tyrosine kinase 3 (Jak3) dependent function in cells of lymphoid or myeloid origin, especially for blocking proliferation and function of lymphocytes (e.g., T-cells, B- cells). A Mannich base compound, or a derivative or modified compound, is employed which is capable of selectively inhibiting Jak3 while affecting other protein tyrosine kinase activities to a lesser extent or not at all, to provide beneficial effects such as mitigation of transplant rejection and alleviation of allergic responses with fewer side effects than with conventional immunosuppressive agents.

La présente invention a trait à des procédés permettant l'inhibition ou l'interruption de la fonction dépendante de la Janus tyrosine kinase 3 (Jak3) dans des cellules d'origine lymphoïde ou myéloïde, notamment pour bloquer la prolifération et la fonction des lymphocytes (par exemple, les lymphocytes T, les lymphocytes B). On utilise un composé de base mannich, ou un dérivé ou un composé modifié, qui est capable d'inhibition sélective de Jak3 tout en affectant d'autres activités de la protéine tyrosine kinase à un moindre degré ou pas du tout, pour procurer des effets bénéfiques tels que l'atténuation de rejet de transplantation ou l'atténuation de réactions allergiques avec moins d'effets secondaires qu'avec des agents immunosuppresseurs classiques.

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