Nitrosated and nitrosylated taxanes, compositions and...

C - Chemistry – Metallurgy – 07 – D

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C07D 305/14 (2006.01) A61K 31/335 (2006.01) A61K 45/06 (2006.01) A61P 9/14 (2006.01) A61P 35/00 (2006.01) C07D 409/12 (2006.01)

Patent

CA 2410632

The present invention describes novel nitrosated and/or nitrosylated taxanes, and novel compositions comprising at least one nitrosated and/or nitrosylated taxane, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The present invention also provides novel compositions comprising at least one taxane and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The compounds and compositions of the present invention can also be bound to a matrix. The present invention also provides methods for treating or preventing cardiovascular diseases and disorders, autoimmune diseases, pathological conditions resulting from abnormal cell proliferation, polycystic kidney disease, inflammatory disease, preserving organs and/or tissues or to inhibit wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis, by administering nitrosated and/or nitrosylated taxane or parent taxanes in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions.

L'invention concerne de nouveaux taxanes nitrosés et/ou nitrosylés, et de nouvelles compositions comprenant au moins un taxane nitrosé et/ou nitrosylé, ainsi que, éventuellement, au moins un composé qui émet, transfère ou libère de l'oxyde nitrique, élève les niveaux endogènes du facteur relaxant dérivé de l'endothélium, stimule la synthèse endogène d'oxyde nitrique ou constitue un substrat pour la synthèse d'oxyde nitrique et/ou au moins un agent thérapeutique. Cette invention concerne également de nouvelles compositions comprenant au moins un taxane et au moins un composé qui émet, transfère ou libère de l'oxyde nitrique, élève les niveaux endogènes du facteur relaxant dérivé de l'endothélium, stimule la synthèse endogène de l'oxyde nitrique ou constitue un substrat pour la synthèse d'oxyde nitrique et/ou au moins un agent thérapeutique. Les composés et compositions de cette invention peuvent également être liés à une matrice. L'invention concerne également des procédés permettant de traiter et de prévenir des maladies et des désordres cardio-vasculaires, des maladies auto-immunes, des conditions pathologiques résultant de la proféliration anormale de cellules, la maladie du rein polykystique, des maladies inflammatoires, de conserver des organes et/ou des tissus, d'empêcher la contraction de plaies, particulièrement dans le traitement prophylactique et/ou thérapeutique de la résténose, par administration de taxane nitrosé et/ou nitrosylé ou de taxanes parents en combinaison avec des donneurs d'oxyde nitrique capables de libérer de l'oxyde nitrique ou d'apporter ou de transférer indirectement de l'oxyde nitrique à des sites ciblés dans des conditions physiologiques.

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