Pteridinones as kinase inhibitors

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 475/00 (2006.01) A61K 31/519 (2006.01)

Patent

CA 2393896

Disclosed are compounds of Formulae (Ia), (Ib), (Ic), (Id) wherein: W is NH, S, SO, or SO2; R2 is (un)substituted aryl, (un)substituted heteroaryl, or (un)substituted carbocycle or heterocycle; Q is hydrogen or lower alkyl; R4 and R6 are the same or different and represent hydrogen, halogen, lower alkyl, lower alkoxy, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted arylalkyl or (un)substituted heteroarylalkyl; and R8 is hydrogen, lower alkyl or an (un)substituted carbocyclic group containing from 3-7 members, up to two of which members are optionally hetero atoms selected from oxygen and nitrogen; or R8 is (un)substituted aryl, (un)substituted heteroaryl, (un)substituted arylalkyl or (un)substituted heteroarylalkyl. These compounds are useful for treating cell proliferative disorders, such as cancer and restenosis. These compounds are potent inhibitors of cyclin- dependent kinases (cdks) and growth factor-mediated kinases. The present invention also provides a method of treating cell proliferative disorders. Also provided by the present invention is a pharmaceutically acceptable composition containing a compound of Formula (I).

La présente invention concerne des composés de formules (Ia), (Ib), (Ic), (Id) dans lesquelles: W est NH, S, SO, ou SO¿2?; R?2¿ est aryle substitué ou non, hétéroaryle substitué ou non, ou un carbocycle ou hétérocycle substitué ou non; Q est hydrogène ou alkyle inférieur; R?4¿ et R?6¿ sont identiques ou différents et représentent hydrogène, halogène, alkyle inférieur, alkoxy inférieur, aryle substitué ou non, hétéroaryle substitué ou non, arylalkyle substitué ou non ou hétéroarylalkyle substitué ou non; et R?8¿ est hydrogène, alkyle inférieur ou un groupe carbocyclique substitué ou non contenant 3 à 7 membres dont un ou deux sont éventuellement des hétéroatomes choisis parmi oxygène et azote; ou R?8¿ est aryle substitué ou non, hétéroaryle substitué ou non, arylalkyle substitué ou non ou hétéroarylalkyle substitué ou non. Ces composés peuvent être utilisés pour le traitement de troubles de prolifération cellulaire tels que le cancer et la resténose. Ces composés sont des inhibiteurs efficaces des kinases cyclino-dépendantes (cdks) et des kinases liées au facteur de croissance. Cette invention concerne également un procédé de traitement de troubles de prolifération cellulaire, ainsi des compositions pharmaceutiquement acceptables contenant un composé de formule (I).

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