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    NOVEL MOLECULES THAT SELECTIVELY INHIBIT HISTONE DEACETYLASE 6 RELATIVE TO HISTONE DEACETYLASE 1
    4.
    发明公开
    NOVEL MOLECULES THAT SELECTIVELY INHIBIT HISTONE DEACETYLASE 6 RELATIVE TO HISTONE DEACETYLASE 1 审中-公开
    的新分子FOR组蛋白脱乙酰6的相对于组蛋白脱乙酰1选择性抑制

    公开(公告)号：EP2763531A4

    公开(公告)日：2015-11-18

    申请号：EP12838935

    申请日：2012-10-03

    申请人： UNIV COLUMBIA ,  SLOAN KETTERING INST CANCER

    发明人： BRESLOW RONALD ,  MARKS PAUL A

    IPC分类号： C07C259/06 ,  A61K31/47 ,  A61P25/28 ,  C07C259/10 ,  C07C275/64 ,  C07D209/08 ,  C07D209/18 ,  C07D209/24 ,  C07D209/42 ,  C07D215/06 ,  C07D215/40 ,  C07D235/06

    CPC分类号： C07C259/10 ,  C07C259/06 ,  C07C275/64 ,  C07C2602/10 ,  C07D209/08 ,  C07D209/18 ,  C07D209/24 ,  C07D209/42 ,  C07D215/06 ,  C07D215/40 ,  C07D235/06

    摘要： This invention provides a compound having the structure: wherein R1 is H, halogen, —NR5R6, —NR5—C(═O)—R6, —NH—C(═O)—OR7, —OR7, —NO2, —CN, —SR7, —SO2R7, —CO2R7, CF3, —SOR7, —POR7, —C(═S)R7, —C(═O)—NR5R6, —CH2—C(═O)—NR5R6, —C(═NR5)R6, —P(═O)(OR5)(OR6), —P(OR5)(OR6), —C(═S)R7, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R5, R6, and R7 and are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R2 and R3 are each, independently, H, halogen, —NH2, —CX3, —C(═O)OR8, C(═O)R8, —C(═O)NR9R10, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R8, R9 and R10 are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar1—Z— or —Z—Ar1—Z—, wherein Ar1 is aryl or heteroaryl; and each occurrence of Z is independently present or absent, and when present is —O—, —S—, —CH2—, —C(O)——NH—, —NH—NH—, —NHC(═O)—, —C(═O)NH—, —NHC(═O)CH2NH—, —NHC(═O)CH2C(═O)—, —N(OH)—, —CH2CH2— or —NHC(═O)CH═CH—; and R4 is alkyl, —OR11 or —NH—OR11, wherein R11 is H, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, and when Q is —Ar1—Z—, Z is absent, Ar1 is phenyl, R2 and R3 are H, n=1, and R4 is —NHOH, then R1 is other than carbazole, tetrahydro-&bgr;-carboline, tetrahydro-γ-carboline, —C(═O)—NR5R6 and —NR5—C(═O)—R6, wherein one of R5 or R6 is quinoline and the other of R5 or R6 is H; or a pharmaceutically acceptable salt thereof.