Pyrimidine Derivatives, their use in the preparation of Drugs, Pharmaceutical compositions comprising such Compounds, Process for preparing such compositions, processes for preparing such Compounds, products containing these Compounds, and intermediaries

摘要

1. Pyridine derivatives (1);N-oxides, pharmaceutically acceptable addition salts, quaternary amines and stereochemically isomeric forms thereof, wherein: -a1 = a2-a3 = a4- represents a divalent radical of the formula -CH = CH-CH = CH - (a-1);-N 3DCH-CH 3DCH- (a-2)-N 3DCH-N 3DCH- (a-3)-N 3DCH-CH 3DN- (a-4)-N 3DN-CH 3DCH- (a-5)-B1 = b2-b3 = B4 - represents a different formula - CH = ch - (B-1);-N 3DCH-CH 3DCH- (b-2)-N 3DCH-N 3DCH- (b-3)-N 3DCH-CH 3DN- (b-4)-N 3DN-CH 3DCH- (b-5)N is 0.1, 2, 3 or 4; if - A1 = A2-A3 = A4 sea (A-1),Then n can also be 5, M is 1, 2, 3, if - B1 = b2-b3 = b4-sea (B-1),then m can also be 4; R1 is hydrogen; aryl; formyl; C1-6 alkylcarbonyl; C1-6 alkyl; C1-6 alkyloxycarbonyl; C1-6 alkyl substituted with formyl, C1-6 alkylcarbonyl, C1-6 alkyloxycarbonyl, C1-6 alkylcarbonyloxy; C1-6 alkyloxy-C1-6 alkylcarbonyl substituted with C1-6 alkyloxycarbonyl; each R2 independently is hydroxy, halo, C1-6 alkyl optionally substituted with cyano or -C (= O) R6, C3-7 cycloalkyl, C2-6 alkenyl optionally substituted with one or more halogen or cyano atoms, C2-6 alkynyl optionally substituted with one or more halogen or cyano atoms, C1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di (C1-6 alkyl) amino,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 (2) where each A1 independently is N, CH or CR6; and A2 is NH, O, S or NR6; X1 is -NR5, -NH-NH-,-N=N- that is...-C (=O)alcanodiilo C1-4 -CHOH-- yes.-S (3DO) p--X2-c1-4 - or - c1-4-x2-alkane;X2 is -NR5.-NH-NH-N=N- that is...-C (=O)-Choh...- yes.-S (3DO) p-R3 is NHR13; NR13R14; -C (= O) -NHR13; -C (= O) -NR13R14; -C (= O) -R15; -CH = N-NH-C (= O) -R16; C1-6 alkyl substituted with one or more substituents each independently selected from cyano, NR9R10, -C (= O) -NR9R10, -C (= O) -C1-6 alkyl or R7; C1-6 alkyl substituted with one or more substituents each independently selected from cyano, NR9R10, -C (= O) -NR9R10, -C (= O) -C1-6 or R7 alkyl and where 2 hydrogen atoms linked thereto Carbon atoms are replaced with C1-4 alkanediyl; C1-6 alkyl substituted with hydroxy and a second substituent selected from cyano, NR9R10, -C (= O) -NR9R10, -C (= O) -C1-6 alkyl or R7;C1-6 alkyloxy-C1-6 alkyl optionally substituted with one or more substituents each independently selected from cyano, NR9R10, -C (= O) -NR9R10, -C (= O) -C 1-6 alkyl or R7; C2-6 alkenyl substituted with one or more substituents each independently selected from halo, cyano, NR9R10, -C (= O) -NR9R10, -C (= O) -C1-6 alkyl or R7; C2-6 alkynyl substituted with one or more substituents each independently selected from halo, cyano, NR9R10, -C (= O) -NR9R10, -C (= O) -C1-6 alkyl or R7; -C (= N-O-R8) -C 1-4 alkyl; R7 or -X3-R7; X3 is -NR5-,-NH-NH-N=N- that is...-C (=O)- yes.-S (3DO) p--X2-C1-4 alkane-C 1-4 alkanediyl-,-C1-4-x2b-c1-4-c (= n-or8) - c1-4-alkane;At x2a - nh-nh--N=N- that is...-C (=O)- yes.-S (3DO) p-Where x2b is - nh-nh--N=N-C (=O)- yes.-S (3DO) p-R4 is halo, hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C1-6 alkyloxy, cyano, nitro, C1-6 polyhaloalkyl, C1-6 polyhaloalkyloxy, aminocarbonyl, C1-6 alkyloxycarbonyl, C1-6 alkylcarbonyl, formyl, amino , mono- or di (C1-4 alkyl) amino or R7;R5 is hydrogen; aryl; formyl; C1-6 alkylcarbonyl; C1-6 alkyl; C1-6 alkyloxycarbonyl; C1-6 alkyl substituted with formyl, C1-6 alkylcarbonyl, C1-6 alkyloxycarbonyl or C1-6 alkylcarbonyloxy; C1-6 alkyloxy-C1-6 alkylcarbonyl substituted with C1-6 alkyloxycarbonyl; R 6 is C 1-4 alkyl, amino, mono- or di (C 1-4 alkyl) amino or C 1-4 polyhaloalkyl; R7 is a saturated, partially saturated or aromatic monocyclic, bicyclic or tricyclic carbocycle or a saturated, partially saturated or aromatic monocyclic, bicyclic or tricyclic heterocycle, where 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, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, mono- or di (C1-6 alkyl) C1-6 aminoalkyl, formyl , C1-6 alkylcarbonyl, C3-7 cycloalkyl, C1-6 alkyloxy, C1-6 alkyloxycarbonyl, C1-6 alkylthio, cyano, nitro, C1-6 polyhaloalkyl, C1-6 polyhaloalkyloxy, aminocarbonyl, -CH (= NO-R8) ,R7a, -X3-R7a or R7a-C1-4 alkyl; R7a is a saturated, partially saturated or aromatic monocyclic, bicyclic or tricyclic carbocycle or a saturated, partially saturated or aromatic monocyclic, bicyclic or tricyclic heterocycle, where 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, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, mono or di (C 1-6 alkyl) C 1-6 aminoalkyl, formyl, C 1 alkylcarbonyl -6, C3-7 cycloalkyl, C1-6 alkyloxy, C1-6 alkyloxycarbonyl, C1-6 alkylthio, cyano,1. Nitric acid, polyalkyl C1-6, polyalkyl C1-6, carbamate HCH (= n-o-r8);R8 is hydrogen, C1-4 alkyl, aryl or C1-4 arylalkyl; R9 and R10 are each independently hydrogen; hydroxy; C1-6 alkyl; C1-6 alkyloxy; C1-6 alkylcarbonyl; C1-6 alkyloxycarbonyl; Not me; mono- or di (C1-6 alkyl) amino; mono- or di (C1-6 alkyl) aminocarbonyl; -CH (= NR11) or R7, where each of the above-mentioned C1-6 alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C1-6 alkyloxy, C1-6 hydroxyalkyloxy , carboxyl, C1-6 alkyloxycarbonyl, cyano, amino, imino, mono- or di (C1-4 alkyl) 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, R7; or R9 and R10 can be taken together to form a divalent or trivalent radical of the 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 3DCH-CH2- (d-6)3DCH-CH 3DCH-CH 3DCH- (d-7)R11 is cyano; C1-4 alkyl optionally substituted with C1-4 alkyloxy, cyano, amino, mono- or di (C1-4 alkyl) amino or aminocarbonyl; C1-4 alkylcarbonyl; C1-4 alkyloxycarbonyl; aminocarbonyl; mono- or di (C1-4 alkyl) aminocarbonyl; R12 is hydrogen or C1-4 alkyl; R13 and R14 each independently are C1-6 alkyl optionally substituted with cyano or aminocarbonyl, C2-6 alkenyl optionally substituted with cyano or aminocarbonyl, C2-6 alkynyl optionally substituted with cyano or aminocarbonyl; R15 is C1-6 alkyl substituted with cyano or aminocarbonyl; R16 is C1-6 alkyl optionally substituted with cyano or aminocarbonyl, or R7; p is 1 or 2;aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, mono or di (C1- alkyl) 6) C1-6 aminoalkyl, C1-6 alkylcarbonyl, C3-7 cycloalkyl, C1-6 alkyloxy, C1-6 alkyloxycarbonyl, C1-6 alkylthio, cyano, nitro, C1-6 polyhaloalkyl, C1-6 polyhaloalkyloxy, aminocarbonyl,-X3-R7. These compounds have the properties of inhibiting the replication of HIV (human immunodeficiency virus) and thus contribute to the prevention or treatment of HIV infection. 3. The use of these compounds in the manufacture of drugs, including the pharmaceutical components of these compounds, the procedures for the preparation of these compounds, the procedures for the preparation of these compounds, products containing these compounds, and useful intermediaries for the synthesis of these compounds.