HIV inhibiting 1,2,4-triazin-6-one derivatives

A compound of formula

• a N-oxide, a pharmaceutically acceptable acid addition salt, or a stereochemically isomeric form thereof, wherein
• ring A represents phenyl;
• ring B represents phenyl;
• n is 1, 2, 3 or 4;
• m is 1, 2, 3 or 4;
• R1 represents hydrogen;
• aryl;
• formyl;
• C1-6alkylcarbonyl;
• C1-6alkyloxycarbonyl;
• C1-6alkyl optionally substituted with R5;
• or C1-6alkyloxyC1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl;
• each R2 independently represents hydrogen;
• hydroxy;
• halo;
• C1-6alkyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy or —C(═O)R6;
• C2-6alkenyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy or —C(═O)R6;
• C2-6 alkynyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy or —C(═O)R6;
• C3-7cycloalkyl;
• C1-6alkyloxy;
• C1-6alkyloxycarbonyl;
• C1-6alkylcarbonyloxy;
• carboxyl;
• cyano;
• nitro;
• amino;
• mono- or di(C1-6alkyl)amino;
• polyhaloC1-4alkyl;
• polyhaloC1-4alkyloxy;
• polyhaloC1-4alkylthio;
• —S(═O)pR6;
• —NH—S(═O)pR6;
• —C(═O)R6;
• —NHC(═O)H;
• —C(═O)NHNH2;
• NHC(═O)R6;
• C(═NH)R6;
• or R7;
• R2a represents cyano;
• aminocarbonyl;
• amino;
• halo;
• NHR13;
• NR13R14;
• —C(═O)—NHR13;
• —C(═O)—NR13R14;
• —C(═O)—R15;
• —CH═N—NH—C(═O)—R16;
• C1-6alkyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• C1-6alkyloxy optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl,
• —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• C1-6alkyloxyC1-6alkyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10,
• —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl,
• —C(═O)—O-polyhaloC1-6alkyl or R7;
• C2-6alkenyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• C2-6alkynyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• —C(═N—O—R8)—C1-4alkyl;
• R7 or —X3—R7;
• X1 represents —NR1—;
• —NH—NH—;
• —N═N—;
• —O—;
• —C(═O)—;
• —C1-4alkanediyl-;
• —CHOH—;
• —S—;
• —S(═O)p—;
• —X4—C1-4alkanediyl-;
• —C1-4alkanediyl-X4—;
• or
• —C1-4alkanediyl-X4—C1-4alkanediyl-;
• X2 represents —NR1—;
• —NH—NH—;
• —N═N—;
• —O—;
• —C(═O)—;
• —C1-4alkanediyl-;
• —CHOH—;
• —S—;
• —S(═O)p—;
• —X4—C1-4alkanediyl-;
• —C1-4alkanediyl-X4—;
• or
• —C1-4alkanediyl-X4—C1-4alkanediyl-;
• X3 represents —NR1—;
• —NH—NH—;
• —N═N—;
• —O—;
• —C(═O)—;
• —S—;
• —S(═O)p—;
• —X4a—C1-4alkanediyl-;
• —C1-4alkanediyl-X4b—;
• —C1-4alkanediyl-X4a—C1-4alkanediyl-;
• or
• —C(═N—OR8)—C1-4alkanediyl-;
• X4 represents —NR1—;
• —NH—NH—;
• —N═N—;
• —O—;
• —C(═O)—;
• —CHOH—;
• —S—;
• or —S(═O)p—;
• X4a represents —NR1—;
• —NH—NH—;
• —N═N—;
• —C(═O)—;
• —S—;
• or —S(═O)p—;
• X4b represents —NH—NH—;
• —N═N—;
• —O—;
• —C(═O)—;
• —S—;
• or —S(═O)p—;
• R3 represents cyano;
• aminocarbonyl;
• amino;
• halo;
• NHR13;
• NR13R14;
• —C(═O)—NHR13;
• —C(═O)—NR13R14;
• —C(═O)—R15;
• —CH═N—NH—C(═O)—R16;
• C1-6alkyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• C1-6alkyloxy optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl,
• —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• C1-6alkyloxyC1-6alkyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10,
• —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl,
• —C(═O)—O-polyhaloC1-6alkyl or R7;
• C2-6alkenyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• C2-6alkynyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl, —C(═O)—O—C1-6alkyl, —C(═O)-polyhaloC1-6alkyl, —C(═O)—O-polyhaloC1-6alkyl or R7;
• —C(═N—O—R8)—C1-4alkyl;
• R7 or —X3—R7;
• each R4 independently represents hydrogen;
• hydroxy;
• halo;
• C1-6alkyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy or —C(═O)R6;
• C2-6alkenyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy or —C(═O)R6;
• C2-6alkynyl optionally substituted with one or more substituents each independently selected from halo, cyano, hydroxy or —C(═O)R6;
• C3-7cycloalkyl;
• C1-6alkyloxy;
• C1-6alkyloxycarbonyl;
• C1-6alkylcarbonyloxy;
• carboxyl;
• cyano;
• nitro;
• amino;
• mono- or di(C1-6alkyl)amino;
• polyhaloC1-4alkyl;
• polyhaloC1-4alkyloxy;
• polyhaloC1-4alkylthio;
• —S(═O)pR6;
• —NH—S(═O)pR6;
• —C(═O)R6;
• —NHC(═O)H;
• —C(═O)NHNH2;
• NHC(═O)R6;
• C(═NH)R6;
• or R7;
• R5 represents formyl, cyano, aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, hydroxy, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl or C1-6alkylcarbonyloxy;
• R6 represents C1-4alkyl, amino, mono- or di(C1-4alkyl)amino or polyhaloC1-4alkyl;
• R7 represents a monocyclic, bicyclic or tricyclic saturated carbocycle;
• a monocyclic, bicyclic or tricyclic partially saturated carbocycle;
• a monocyclic, bicyclic or tricyclic aromatic carbocycle;
• a monocyclic, bicyclic or tricyclic saturated heterocycle;
• a monocyclic, bicyclic or tricyclic partially saturated heterocycle;
• or a monocyclic, bicyclic or tricyclic aromatic heterocycle;
• wherein each of said carbocyclic or heterocyclic ring systems may, whenever possible, optionally be substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono or di(C1-6alkyl)aminoC1-6alkyl, formyl, C1-6alkylcarbonyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, C1-6alkylthio, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, —CH(═N—O—R8), R7a, —X3—R7a or R7a—C1-4alkanediyl-;
• R7a represents a monocyclic, bicyclic or tricyclic saturated carbocycle;
• a monocyclic, bicyclic or tricyclic partially saturated carbocycle;
• a monocyclic, bicyclic or tricyclic aromatic carbocycle;
• a monocyclic, bicyclic or tricyclic saturated heterocycle;
• a monocyclic, bicyclic or tricyclic partially saturated heterocycle;
• or a monocyclic, bicyclic or tricyclic aromatic heterocycle;
• wherein each of said carbocyclic or heterocyclic ring systems may optionally be substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto,
• C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono or
• di(C1-6alkyl)aminoC1-6alkyl, formyl, C1-6alkylcarbonyl, C3-7cycloalkyl, C1-6alkyloxy,
• C1-6alkyloxycarbonyl, C1-6alkylthio, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, —CH(═N—O—R8);
• R8 represents hydrogen, C1-4alkyl optionally substituted with aryl, or aryl;
• R9 and R10 each independently represent hydrogen;
• hydroxy;
• C1-6alkyl;
• C1-6alkyloxy;
• C1-6alkylcarbonyl;
• C1-6alkyloxycarbonyl;
• amino;
• mono- or di(C1-6alkyl)amino;
• mono- or di(C1-6alkyl)aminocarbonyl;
• —CH(═NR11) or R7, wherein each of the aforementioned C1-6alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy,
• C1-6alkyloxy, hydroxyC1-6alkyloxy, carboxyl, C1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C1-4alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio,
• —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6, or R7;
• or
• R9 and R10 may be taken together to form a bivalent radical of formula
• —CH2—CH2—CH2—CH2— (d-1)
• —CH2—CH2—CH2—CH2—CH2— (d-2)
• —CH2—CH2—O—CH2—CH2— (d-3)
• —CH2—CH2—S—CH2—CH2— (d-4)
• —CH2—CH2—NR12—CH2—CH2— (d-5)
• —CH2—CH═CH—CH2— (d-6)
• R11 represents cyano;
• C1-4alkyl optionally substituted with C1-4alkyloxy, cyano, amino, mono- or di(C1-4alkyl)amino or aminocarbonyl;
• C1-4alkylcarbonyl;
• C1-4alkyloxycarbonyl;
• aminocarbonyl;
• mono- or di(C1-4alkyl)aminocarbonyl;
• R12 represents hydrogen or C1-4alkyl;
• R13 and R14 each independently represent C1-6alkyl optionally substituted with cyano or aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl, C2-6alkenyl optionally substituted with cyano or aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl, C2-6alkynyl optionally substituted with cyano or aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• R15 represents C1-6alkyl optionally substituted with cyano or aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• R16 represents C1-6alkyl optionally substituted with cyano or aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl, or R7;
• p is 1 or 2;
• aryl represents phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono or di(C1-6alkyl)aminoC1-6alkyl,
• C1-6alkylcarbonyl,
• C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, C1-6alkylthio, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, R7 or —X3—R7.