Pyrido[2,3-d]pyrimidine-2,7-diamine kinase inhibitors

C - Chemistry – Metallurgy – 07 – D

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C07D 471/04 (2006.01) A61K 31/519 (2006.01)

Patent

CA 2397961

Disclosed are compounds of the formula (I) wherein: R2, R7, R13, R14 and R15 are independently hydrogen, or (un)sub-stituted lower alkyl, (un)substitued lower alkenyl, (un)substituted lower alkynyl, or (un)substituted -(CH2)n R12; R5 is halogen, cyano, nitro, -R9, -NR9R10, or -OR9; R6 is halogen, cyano, nitro, -R9, -NR9R10, -OR9, -Co2R9, -COR9, -CONR9R10, -NR9COR10, (un)substi-tuted lower alkenyl, or (un)substituted lower alkynyl; R8 is - CO2R13, -COR13, -CONR13R14, -CSNR13R14, -C(NR13)NR14R15, -SO3R13, -SO2R13, -SO2NR13R14, -PO3R13R14, -POR13R14, -PO(NR13R14)2; R9 and R10 are independently hydrogen or (un)substituted lower alkyl; R11 is a heteroaryl or a heterocyclic group; R12 is a cycloalkyl, a heterocyclic, an aryl, or a heteroaryl group; and n is 0,1,2, or 3. These compounds and their pharmaceutical compositions are useful for treating cell proliferative disorders, such as cancer and restenosis. These compounds are potent inhibitors of cdks and growth factor- mediated kinases.

L'invention concerne des composés de la formule: dans laquelle R<2>, R<7>, R<13>, R<14> et R15 sont indépendamment hydrogène, ou alkyle inférieur substitué (non substitué), alcényle inférieur substitué (non substitué), alkynyle inférieur substitué (non substitué), ou (CH2)nR<12> substitué (non substitué); R<5> est halogène, cyano, nitro, -R<9>, -NR<9>R<10>, -OR<9>; R<6> est halogène, cyano, nitro, -R<9>, -NR<9>R<10>, -OR<9>, -CO2R<9>, -COR<9>, -CONR<9>R<10>, -NR<9>COR<10>, alcényle inférieur substitué (non substitué) ou alkynyle inférieur substitué (non substitué); R<8> est -CO2R<13>, -COR<13>, -CONR<13>R<14>, -CSNR<13>R<14>, -C(NR<13>)NR<14>R<15>, -SO3R<13>, -SO2R<13>, -SO2NR<13>R<14>, -PO3R<13>R<14>, -POR<13>R<14>, -PO(NR<13>R<14>)2; R<9> et R<10> sont indépendamment hydrogène ou alkyle inférieur substitué (non substitué); R<11> est un hétéroaryle ou un groupe hétérocyclique; R<12> est un cycloalkyle, un hétérocyclique, un aryle ou un groupe hétéroaryle ; et n représente 0,1,2, ou 3. Ces composées et leurs compositions pharmaceutiques s'avèrent utiles pour traiter des troubles de prolifération cellulaire, tels que le cancer et la resténose. Lesdits composés sont des inhibiteurs efficaces des kinases cyclino-dépendantes (cdks) et des kinases liées au facteur de croissance.

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