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    Pyrido-, Pyrazo- and Pyrimido-Pyrimidine Derivatives as mTOR Inhibitors
    4.
    发明申请
    Pyrido-, Pyrazo- and Pyrimido-Pyrimidine Derivatives as mTOR Inhibitors 审中-公开

    公开(公告)号：US20080194546A1

    公开(公告)日：2008-08-14

    申请号：US11842927

    申请日：2007-08-21

    申请人： Marc Geoffrey Hummersone ,  Gomez Sylvie ,  Keith Allan Menear ,  Graeme Cameron Murray Smith ,  Karine Malagu ,  Heather Mary Ellen Duggan ,  Niall Morrison Barr Martin ,  Frederic Georges Marie Leroux ,  Gesine Johanna Hermann ,  Xiao-Ling Fan Cockcroft

    发明人： Marc Geoffrey Hummersone ,  Gomez Sylvie ,  Keith Allan Menear ,  Graeme Cameron Murray Smith ,  Karine Malagu ,  Heather Mary Ellen Duggan ,  Niall Morrison Barr Martin ,  Frederic Georges Marie Leroux ,  Gesine Johanna Hermann ,  Xiao-Ling Fan Cockcroft

    IPC分类号： A61K31/5377 ,  C07D413/14 ,  A61K31/5513 ,  A61P35/00 ,  C07D243/14

    CPC分类号： C07D475/08 ,  C07D475/06 ,  C07D487/04

    摘要： There is provided a compound of formula I: wherein: one or two of X5, X6 and X8 is N, and the others are CH; R7 is selected from halo, ORO1, SRS1, NRN1RN2, NRN7aC(═O)RC1, NRN7bSO2RS2a, an optionally substituted C5-20 heteroaryl group, or an optionally substituted C5-20 aryl group, where RO1 and RS1 are selected from H, an optionally substituted C5-20 aryl group, an optionally substituted C5-20 heteroaryl group, or an optionally substituted C1-7 alkyl group; RN1 and RN2 are independently selected from H, an optionally substituted C1-7 alkyl group, an optionally substituted C5-20 heteroaryl group, an optionally substituted C5-20 aryl group or RN1 and RN2 together with the nitrogen to which they are bound form a heterocyclic ring containing between 3 and 8 ring atoms; RC1 is selected from H, an optionally substituted C5-20 aryl group, an optionally substituted C5-20 heteroaryl group, an optionally substituted C1-7 alkyl group or NRN8RN9, where RN8 and RN9 are independently selected from H, an optionally substituted C1-7 alkyl group, an optionally substituted C5-20 heteroaryl group, an optionally substituted C5-20 aryl group or RN8 and RN9 together with the nitrogen to which they are bound form a heterocyclic ring containing between 3 and 8 ring atoms; RS2a is selected from H, an optionally substituted C5-20 aryl group, an optionally substituted C5-20 heteroaryl group, or an optionally substituted C1-7 alkyl group; RN7a and RN7b are selected from H and a C1-4 alkyl group; RN3 and RN4, together with the nitrogen to which they are bound, form a heterocyclic ring containing between 3 and 8 ring atoms; R2 is selected from H, halo, ORO2, SRS2b, NRN5RN6, an optionally substituted C5-20 heteroaryl group, and an optionally substituted C5-20 aryl group, wherein RO2 and RS2b are selected from H, an optionally substituted C5-20 aryl group, an optionally substituted C5-20 heteroaryl group, or an optionally substituted C1-7 alkyl group; RN5 and RN6 are independently selected from H, an optionally substituted C1-7 alkyl group, an optionally substituted C5-20 heteroaryl group, and an optionally substituted C5-20 aryl group, or RN5 and RN6 together with the nitrogen to which they are bound form a heterocyclic ring containing between 3 and 8 ring atoms, or a pharmaceutically acceptable salt thereof, with the proviso that when R2 is unsubstituted morpholino. RN3 and RN4 together with the nitrogen atom to which they are attached form an unsubstituted morpholino and R7 is unsubstituted phenyl, and X5 is CH, then X6 is not N and X8 is not CH, or X6 is not CH and X8 is not N, and when R2 is unsubstituted piperidinyl, RN3 and RN4 together with the nitrogen atom to which they are attached form an unsubstituted piperidinyl and R7 is unsubstituted phenyl, and X5 is CH, then X6 is not CH and X is not N. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.