HIV replication inhibiting purine derivatives

A compound of formula

• or a pharmaceutically acceptable addition salt, or a stereochemically isomeric form thereof, wherein
• A and B each represents a radical of formula
• wherein
• ring E represents phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl;
• ring F represents phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl;
• R1 represents hydrogen;
• aryl;
• formyl;
• C1-6alkylcarbonyl;
• C1-6alkyloxycarbonyl;
• C1-6alkyl optionally substituted with formyl, C1-6alkylcarbonyl,
• C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy;
• or C1-6alkyloxyC1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl;
• R2 represents cyano;
• C1-6alkyl substituted with cyano, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• C2-6alkenyl substituted with cyano, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• or C2-6alkynyl substituted with cyano, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• X1 represents —NR5—;
• —NH—NH—;
• —N═N—;
• —O—;
• —C(═O)—;
• —C1-4alkanediyl-;
• —CHOH—;
• —S—;
• —S(═O)p—;
• —X2—C1-4alkanediyl-;
• —C1-4alkanediyl-X2—;
• or
• —C1-4alkanediyl-X2—C1-4alkanediyl-;
• X2 represents —NR5—;
• —NH—NH—;
• —N═N—;
• —O—;
• —C(═O)—;
• —CHOH—;
• —S—;
• or —S(═O)p—;
• m represents an integer of value 1, 2, 3 or 4;
• 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 R3a;
• C1-6alkyloxy optionally substituted with one or more substituents each independently selected from R3a;
• C1-6alkyloxyC1-6alkyl optionally substituted with one or more substituents each independently selected from R3a;
• C2-6alkenyl optionally substituted with one or more substituents each independently selected from R3a;
• C2-6alkynyl optionally substituted with one or more substituents each independently selected from R3a;
• —C(═N—O—R8)—C1-4alkyl;
• R7 or —X3—R7;
• R3a represents 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;
• X3 represents —NR5—;
• —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-;
• X4a represents —NR5—;
• —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—;
• each R4 independently represents hydroxy;
• halo;
• C1-6alkyl optionally substituted with one or more substituents each independently selected from R4a;
• C2-6alkenyl optionally substituted with one or more substituents each independently selected from R4a;
• C2-6alkynyl optionally substituted with one or more substituents each independently selected from R4a;
• C3-7cycloalkyl;
• C1-6alkyloxy;
• C1-6alkyloxycarbonyl;
• C1-6alkylcarbonyloxy;
• carboxyl;
• formyl;
• cyano;
• nitro;
• amino;
• mono- or
• di(C1-6alkyl)amino;
• polyhaloC1-6alkyl;
• polyhaloC1-6alkyloxy;
• polyhaloC1-6alkylthio;
• —S(═O)pR6;
• —NH—S(═O)pR6;
• —C(═O)R6;
• —NHC(═O)H;
• —C(═O)NHNH2;
• NHC(═O)R6;
• C(═NH)R6;
• or R7;
• R4a represents halo, cyano, NR9R10, hydroxy or —C(═O)R6;
• R5 represents hydrogen;
• aryl;
• formyl;
• C1-6alkylcarbonyl;
• C1-6alkyloxycarbonyl;
• C1-6alkyl optionally substituted with formyl, C1-6alkylcarbonyl,
• C1-6alkyloxycarbonyl or C1-6alkylcarbonyloxy;
• or C1-6alkyloxyC1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl;
• R6 represents C1-6alkyl, 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, 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;
• 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);
• or
• —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, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• C2-6alkenyl optionally substituted with cyano, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• C2-6alkynyl optionally substituted with cyano, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• R15 represents C1-6alkyl optionally substituted with cyano, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• R16 represents C1-6alkyl optionally substituted with cyano, aminocarbonyl or mono- or di(C1-4alkyl)aminocarbonyl;
• or R7;
• —C-D- represents a bivalent radical of formula
• —N═CH—NR17— (c-1);
• or
• —NR17—CH═N— (c-2);
• R17 represents hydrogen;
• C1-6alkyl optionally substituted with hydroxy, cyano, aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, C1-4alkyloxycarbonyl or aryl;
• p represents an integer of value 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;
• provided that when A represents a radical of formula (a) then B represents a radical of formula (b) and when A represents a radical of formula (b) then B represents a radical of formula (a).