Hiv replication inhibiting pyrimidines and triazines

A compound of formula (I)

• a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein
• -a1=a2-a3=a4- represents a bivalent radical of formula
• —CH═CH—CH═CH— (a-1);
• —N═CH—CH═CH— (a-2);
• —N═CH—N═CH— (a-3);
• —N═CH—CH═N— (a-4);
• —N═N—CH═CH— (a-5);
• -b1-b2-b3- represents a bivalent radical of formula
• —CH2—CH2—CH2— (b-1);
• n is 0, 1, 2, 3 or 4;
• and in case -a1=a2-a3=a4- is (a-1), then n may also be 5;
• m is 0, 1, 2, 3;
• q is 0, 1 or 2;
• p is 1 or 2;
• R1 is hydrogen;
• aryl;
• formyl;
• C1-6alkylcarbonyl;
• C1-6alkyl;
• C1-6alkyloxycarbonyl;
• C1-6alkyl substituted with formyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy;
• C1-6alkyloxyC1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl;
• each R2 independently is hydroxy, halo, C1-6alkyl optionally substituted with cyano or with —C(═O)R6, C3-7cycloalkyl, C2-6alkenyl optionally substituted with one or more halogen atoms or cyano, C2-6alkynyl optionally substituted with one or more halogen atoms or cyano, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, NR13R14, polyhalomethyl, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6,—C(═NH)R6 or a radical of formula
• wherein each A1 independently is N, CH or CR6;
• and
• A2is NH, O, S or NR6;
• X1 is —NR5—, —NH—NH—, —N═N—, —O—, —C(═O)—, C1-4alkanediyl, —CHOH—, —S—, —S(═O)p—, —NR13—C(═O)—, —C(═O)—NR13—, —X2—C1-4alkanediyl- or —C1-4alkanediyl-X2—;
• X2 is —NR5—, —NH—NH—, —N═N—, —O—, —C(═O)—, —CHOH—, —S—, —S(═O)p—;
• R3 is hydrogen, halo, C1-6alkyl, NR13R14, —C(═O)—NR13R14, —C(═O)—R15, —CH═N—NH—C(═O)—R16, —C(═N—O—R8)-C1-4alkyl, R7 or —X3—R7;
• or C1-6alkyl substituted with one or more substituents each independently selected from halo, hydroxy, cyano, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl or R7, and in addition to said list of substituents, two geminal hydrogen atoms of said C1-6alkyl may also be replaced by a C2-5alkanediyl thus forming a spiro ring;
• C1-6alkyloxyC1-6alkyl optionally substituted with one or more substituents each independently selected from hydroxy, cyano, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl or R7;
• C2-6alkenyl substituted with one or more substituents each independently selected from halo, hydroxy, cyano, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl or R7;
• C2-6alkynyl substituted with one or more substituents each independently selected from halo, hydroxy, cyano, NR9R10, —C(═O)—NR9R10, —C(═O)—C1-6alkyl or R7;
• X3 is —NR5—, —NH—NH—, —N═N—, —O—, —C(═O)—, —S—, —S(═O)p—, —X2—C1-4alkanediyl-, —C1-4alkanediyl-X2a—, —C1-4alkanediyl-X2b-C1-4alkanediyl, —C(═N—OR8)—C1-4alkanediyl-;
• with X2a being —NH—NH—, —N═N—, —O—, —C(═O)—, —S—, —S(═O)p—;
• and
• with X2b being —NH—NH—, —N═N—, —C(═O)—, —S—, —S(═O)p—;
• R4 is halo, hydroxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, —C(═O)—NR13R14, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, —NR13R14 or R7;
• R5 is hydrogen;
• aryl;
• formyl;
• C1-6alkylcarbonyl;
• C1-6alkyl;
• C1-6alkyloxycarbonyl;
• C1-6alkyl substituted with formyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl or C1-6alkylcarbonyloxy;
• C1-6alkyloxyC1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl;
• R6 is C1-4alkyl, NR13R4 or polyhaloC1-4alkyl;
• R7 is a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic saturated, partially saturated or 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), R7a, —X3—R7a or R7a—C1-4alkyl;
• R7a is a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic saturated, partially saturated or 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, —C(═O)—NR13R14, —CH(═N—O—R8);
• R8 is hydrogen, C1-4alkyl, aryl, arylC1-4alkyl;
• R9 and R10 each independently are hydrogen;
• hydroxy;
• C1-6alkyl;
• C1-6alkyloxy;
• C1-6alkylcarbonyl;
• C1-6alkyloxycarbonyl;
• NR13R14;
• —C(═O)—NR13R14;
• —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, carboxylC1-6alkyloxycarbonyl, cyano, imino, NR13R14, 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, R7;
• or
• R9 and R10 may be taken together to form a bivalent or trivalent 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—NR—CH2—CH2— (d-5)
• —CH2—CH═CH—CH2— (d-6)
• ═CH—CH═CH—CH═CH— (d-7)
• R11 is cyano;
• C1-4alkylcarbonyl;
• C1-4alkyloxycarbonyl;
• —C(═O)—NR13R14;
• or C1-4alkyl optionally substituted with C1-4alkyloxy, cyano, NR13R14 or —C(═O)—NR13R14;
• R12 is hydrogen or C1-4alkyl;
• R13 and R14 each independently are hydrogen, Het, C1-6alkyl optionally substituted with cyano or aminocarbonyl, C2-6alkenyl optionally substituted with cyano or aminocarbonyl, C2-6alkynyl optionally substituted with cyano or aminocarbonyl;
• R15 is C1-6alkyl optionally substituted with cyano or —C(═O)—NR13R14;
• R16 is R7 or C1-6alkyl optionally substituted with cyano or —C(═O)—NR13R14;
• R17, if present, each independently is cyano, halo, hydroxy, —C(═O)—NR13R14, C1-6alkyl optionally substituted with one or more substituents independently selected from cyano, —C(═O)—NR13R14 or halo;
• C2-6alkenyl optionally substituted with one or more substituents independently selected from cyano, —C(═O)—NR13R14 or halo;
• C2-6alkynyl optionally substituted with one or more substituents independently selected from cyano, —C(═O)—NR13R14 or halo;
• and, where possible, R17 may also be attached to the -b1-b2-b3- moiety by a double bond whereby R17 is then ═O, ═S, ═NH, ═N—R15, ═N—R7, ═N—O—R15, ═N—O—R7, ═CH2, ═CH—C(═O)—NR13R14, ═CH—R7, or ═CH—R15;
• wherein ═CH2 may optionally be substituted with cyano, hydroxy, halo, nitro;
• Q represents hydrogen, C1-6alkyl, halo, polyhaloC1-6alkyl, —C(═O)—NR13R14, or —NR9R10;
• Z is C—Y, wherein,
• Y represents hydrogen, hydroxy, halo, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carbonyl, cyano, nitro, NR13R14, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR8, —NH—S(═O)R8, —NH—SO2—R8, —NH—SO2—(C1-4alkanediyl)-CO-—(R8)2, —C(═O)R8, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R8, —C(═O)—NH—R8, —C(═NH)R8, aryl;
• or C2-6alkenyl optionally substituted with one or more halo atoms;
• C2-6alkynyl optionally substituted with one ore more halo atoms;
• C1-6alkyl substituted with cyano or with —C(═O)R8;
• aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkylNR13R14, C1-6alkylcarbonyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, C1-6alkylthio, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, —C(═O)—NR13R14, R7 or —X3—R7;
• Het is a monocyclic, bicyclic or tricyclic saturated, partially saturated or 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, —C(═O)—NR13R14, —CH(═N—O—R8).