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    Thrombin inhibitors
    16.
    发明授权
    Thrombin inhibitors 有权
    凝血酶抑制剂

    公开(公告)号：US09469608B2

    公开(公告)日：2016-10-18

    申请号：US14443470

    申请日：2013-11-15

    Applicant: Merck Sharp & Dohme Corp.

    Inventor： Harry Chobanian ,  Tesfaye Biftu ,  Barbara Pio ,  Zhicai Wu

    IPC: C07D207/16 ,  C07D207/34 ,  C07D401/14 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  C07D403/06 ,  C07D417/06

    CPC classification number: C07D207/16 ,  C07D207/34 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06 ,  C07D417/06

    Abstract: Compounds of the invention, which may be useful in inhibiting thrombin and associated thrombotic occlusions, have the following structure: or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1; R is a heterocycle, —(CR8R9)1-2NH2, or —(CR8R9)1-2OH, wherein R8and R9, each time in which they occur, are independently H, C1-6alkyl, —CH2F, —CHF2, CF3or —CH2OH; W is a) —CHR1R2, where R1is —C(CH3)3, and R2is —(CH2)1-2OH, b) a 5- or 6-membered unsubstituted or substituted heterocycle having 1 or 2 heteroatoms selected from N and O, wherein substituted heterocycle is substituted with R3, c) a 9- or 10-membered unsubstituted or substituted heterocycle having 1 or 2 heteroatoms selected from N, O and S, wherein substituted heterocycle is mono-substituted with R3, or disubstituted with R3and R4, or d) a 3-, 4-, or 5-membered carbocyclic ring which is unsubstituted, mono-substituted with R3, di-substituted with R3and R4, or tri-substituted with R3, R4and R5; R3is —CF3, —COOH, —COOR7, —C(O)R6, —CH(OH)R6, —CH2R6, R6, ═O, halogen, R7, —OH, —NH2, or —NHSO2R7; and R10is H or C1-6alkyl.

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