Protein kinase inhibitors comprising atp mimetics conjugated...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 7/06 (2006.01) A61K 31/47 (2006.01) A61K 31/472 (2006.01) A61K 38/03 (2006.01) A61K 38/07 (2006.01) A61K 38/08 (2006.01) A61K 47/48 (2006.01) C07D 217/00 (2006.01) C07K 4/00 (2006.01) C07K 7/00 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2455602

The present invention provides small molecules having high affinity to the ATP binding site of protein kinases, which are conjugated to apeptide or peptidomimetic moiety which mimics the substrate of PKB. The chimeric compounds according to the present invention preferably serve as PKB inhibitors with improved activity and selectivity. Novel ATP mimetic compounds , particularly isoquinoline derivatives, conjugated with peptides or peptidomimetics are useful as inhibitors of protein kinases for experimental, medical, and drug design purposes. Furthermore, pharmaceutical compositions comprising these protein kinase inhibitors, and methods of using such compositions for treatment and diagnosis of cancers, diabetes, cardiovascular pathologies, hemorrhagic shock, obesity, inflammatory diseases, diseases of the central nervous system, and autoimmune disease, are disclosed.

L'invention concerne de petites molécules présentant une affinité élevée pour le site de liaison ATP des protéines kinases (PKB) conjuguées à une fraction de peptide ou de peptidomimétique qui mime le substrat de PKB. Les composés chimériques de l'invention servent, de préférence, d'inhibiteurs de PKB possédant une activité et une sélectivité améliorées. On utilise de nouveaux composés mimétiques de ATP, notamment des dérivés d'isoquinoline conjugués avec des peptides ou des peptidomimétiques comme inhibiteurs des protéines kinases à des fins expérimentales, médicales et de conception de médicaments. L'invention concerne également des compositions pharmaceutiques comprenant des inhibiteurs de protéine kinase, et des méthodes d'utilisation de ces compositions pour traiter et diagnostiquer les cancers, les diabètes, les pathologies cardio-vasculaires, les chocs hémorragiques, l'obésité, les maladies inflammatoires, les maladies du système nerveux central, et les maladies auto-immunes.

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