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PYRIMIDINE DERIVATIVES AS PI3K INHIBITOR AND USE THEREOF

  • US 20100069629A1
  • Filed: 08/07/2007
  • Published: 03/18/2010
  • Est. Priority Date: 08/08/2006
  • Status: Active Grant
First Claim
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1. A compound, represented by the following formula (I):

  • [wherein,X represents a single bond, or a linking group selected from —

    CO—

    , —

    SO2

    , —

    CS—

    or —

    CH2

    ;

    Y represents a single bond or a divalent linking group derived from a ring selected from benzene, pyridine, pyrimidine, pyrazole, imidazole, oxazole, thiazole, furan, thiophene, quinoline, benzoimidazole, benzothiazole, benzopyrazole, naphthalene and benzothiophene (said linking group may be unsubstituted or substituted at 1 to 6 locations by a halogen atom, —

    C1-6 alkyl or —

    OC1-6 alkyl);

    X and Y are not simultaneously single bonds;

    Z represents a hydrogen atom or a substituent selected from the following group A;

    Group A;



    C1-6alkyl, -ethynyl, -halogenoC1-6alkyl, -Cyc, —

    C1-6alkylene-OR, —

    C1-6alkylene-COR, —

    C1-6alkylene-COOR, —

    C1-6alkylene-CONRR′

    , C1-6alkylene-NRR′

    , —

    C1-6alkylene-Cyc, —

    C1-6alkylene-CO-Cyc, —

    C1-6alkylene-O—

    C1-6alkylene-Cyc, —

    C1-6alkylene-SO2R, —

    C1-6alkylene-SO2-Cyc, -halogen, —

    CN, —

    SO2R, —

    SO2

    NRR′

    , —

    SO2

    NR-Cyc, —

    SO2

    NR—

    C1-6alkylene-Cyc, —

    SO2-Cyc, —

    COR, —

    CO-Cyc, —

    CO-Cyc-C1-6alkylene-Cyc, —

    CO—

    C1-6alkylene-Cyc, —

    CO-Cyc-Cyc, —

    COOR, —

    CONRR′

    , —

    CONR—

    C1-6alkylene-OR′

    , —

    CONR—

    C6alkylene-CONR′

    R″

    , —

    CONR-Cyc, —

    CONR—

    C1-6alkylene-Cyc, —

    OR, —

    O-allyl, —

    O-halogenoC1-6alkyl, —

    O—

    C1-6alkylene-NRR′

    , —

    O—

    C1-6alkylene-CONRR′

    , —

    O—

    C6alkylene-NRCOR′

    , —

    NRR′

    , —

    NH—

    NH2, —

    NRCOR′

    , —

    NRCO-Cyc, —

    NRCO—

    C1-6alkylene-Cyc, —

    NRCO—

    C1-6alkylene-OR′

    , —

    NR—

    C1-6alkylene-C OR′

    , —

    NR—

    C1-6alkylene-CONR′

    R″

    , —

    NR—

    C1-6alkylene-NR′

    R″

    , —

    NR—

    C1-6alkylene-NR′

    COR″

    , —

    NR—

    C1-6alkylene-OR′

    , —

    NR-Cyc, —

    NR-Cyc-Cyc, —

    NR-Cyc-CO-Cyc, —

    NR-Cyc-CO—

    C1-6alkylene-Cyc, —

    NR-Cyc-NR′

    -Cyc, —

    NR-Cyc-NR′

    -C1-6alkylene-Cyc, —

    NR—

    C1-6alkylene-Cyc, —

    NR—

    C1-6alkylene-Cyc-CO-Cyc, —

    NR—

    C1-6alkylene-Cyc-NR′

    -Cyc, —

    NRSO2R′

    , —

    S—

    C1-6alkylene-CO-Cyc, —

    S—

    C1-6alkylene-COOR′

    , —

    S—

    C1-6alkylene-NRCOR′

    , and —

    S—

    C1-6alkylene-CONRR′

    ;

    m represents an integer of 1 or 2;

    R1 represents a cyclic substituent selected from the following group having n substituents T;

    A1, A2 and A3 are respectively and independently selected from NH, S or O;

    T represents a substituent selected from the following group B;

    Group B;

    -Cyc, —

    C1-6alkyl, —

    C1-6alkylene-OR, —

    C1-6alkylene-NRR′

    , —

    C1-6alkylene-CONRR′

    , —

    C1-6alkylene-NRCOR′

    , —

    C1-6alkylene-Cyc, —

    OR, —

    O-halogenoC1-6alkyl, —

    O—

    C1-6alkylene-Cyc, —

    O—

    COOR, —

    O—

    COR, —

    O—

    CONRR′

    , —

    NRR′

    , —

    NR—

    C1-6alkylene-NR′

    R″

    , —

    NR—

    C1-6alkylene-OR′

    , -halogen, —

    CO-Cyc, —

    CO-Cyc-Cyc, —

    CO—

    C1-6alkylene-Cyc, —

    COOR, —

    COO—

    C1-6alkylene-OR, —

    COO—

    C6alkylene-NRR′

    , —

    COO—

    C1-6alkylene-Cyc, —

    CONRR′

    , —

    CONR—

    C1-6alkylene-OR′

    , —

    CONR—

    C1-6alkylene-NR′

    R″

    , —

    CONR—

    C1-6alkylene-CONR′

    R″

    , —

    CONR-Cyc, —

    CONR—

    C1-6alkylene-Cyc, —

    SO2NRR′

    , —

    NRSO2R′

    , —

    CN, and —

    NH—

    NH2;

    n represents an integer of 0, 1, 2, 3, 4 or 5 (T may be the same or different when n is 2 to

         5);

    in the aforementioned group A and group B,R, R′ and

    R″

    may be respectively and independently the same or different and represent a hydrogen atom or a —

    C1-6 alkyl (said —

    C1-6 alkyl may be substituted by a group selected from —

    OH, —

    O(C1-6 alkyl), —

    COOH, —

    COO(C1-6 alkyl), —

    CONH2, —

    CONH(C1-6 alkyl), —

    CON(C1-6 alkyl)2, —

    NHCO(C1-6 alkyl), —

    NH2, —

    NH(C1-6 alkyl) and —

    N(C1-6 alkyl)2);

    Cyc represents a hydrocarbon ring or nitrogen-containing heterocyclic ring (said hydrocarbon ring and nitrogen-containing heterocylic ring may be substituted at 1 to 3 locations by a group selected from —

    R(R is not a hydrogen atom at this time), —

    CO—

    R, —

    COOR, —

    CONRR′

    , —

    NRCOR′

    , -halogeno C1-6 alkyl, halogen atom, —

    OR, —

    O-halogeno C1-6 alkyl, —

    NRR′ and



    SO2R);

    said C1-6 alkylene in the groups A and B may be substituted at 1 to 3 locations by a group selected from —

    C1-6 alkyl, —

    OH, —

    CONH2, —

    NH2, —

    NH(C1-6 alkyl) and —

    N(C1-6 alkyl)2; and

    R, R′ and

    R″

    in said —

    NRR′

    , —

    NR′

    R″

    or —

    CONRR′

    in the group A, group B and Cyc may form a 3- to 7-member nitrogen-containing saturated hydrocarbon ring together with an adjacent N] or a pharmaceutically acceptable salt thereof.

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