Patent IL-160328-A (IL)
Title: Pyrimidine derivatives, process and intermediates for preparation thereof and pharmaceutical compositions comprising them for inhibiting hiv
IPC: A61K31/5355
Filed: 2004-02-11
Abstract: This invention concerns HIV replication inhibitors of formula (I) the <i>N</i>-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a<1>=a<2>-a<3>=a<4>- and -b<1>=b<2>-b<3>=b<4>- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl;n is 0 to 5; m is 1 to 4; R<1> is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C<1-6>alkyl; C1-6alkyloxycarbonyl, substituted C1-6alkyl, C1-6alkylcarbonyl; R<2> is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S(=O)pR<6>, -NH-S(=O)pR<6>, -C(=O)R<6>, -NHC(=O)H, -C(=O)NHNH<2?, -NHC(=O)R?6>, -C(=NH)R<6> or a 5-membered heterocycle; X1 is -NR<5>-, -NH-NH-, -N=N-, -O-, -C(=O)-, C1-4alkanediyl, -CHOH-, -S-, -S(=O)p-, -X2-C1-4alkanediyl- or -C1-4alkanediyl-X2-; R<3> is NHR<13>; NR<13>R<14>; -C(=O)-NHR<13>; -C(=O)-NR<13>R<14>; -C(=O)-R<15>; -CH=N-NH-C(=O)-R<16>; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; -C(=N-O-R<8>)-C1-4alkyl; R<7>; or -X3-R<7>; R<4> is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.
This invention concerns HIV replication inhibitors of formula (I) the N -oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a<1>=a<2>-a<3>=a<4>- and -b<1>=b<2>-b<3>=b<4>- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl;n is 0 to 5; m is 1 to 4; R<1> is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C<1-6>alkyl; C1-6alkyloxycarbonyl, substituted C1-6alkyl, C1-6alkylcarbonyl; R<2> is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S(=O)pR<6>, -NH-S(=O)pR<6>, -C(=O)R<6>, -NHC(=O)H, -C(=O)NHNH<2?, -NHC(=O)R?6>, -C(=NH)R<6> or a 5-membered heterocycle; X1 is -NR<5>-, -NH-NH-, -N=N-, -O-, -C(=O)-, C1-4alkanediyl, -CHOH-, -S-, -S(=O)p-, -X2-C1-4alkanediyl- or -C1-4alkanediyl-X2-; R<3> is NHR<13>; NR<13>R<14>; -C(=O)-NHR<13>; -C(=O)-NR<13>R<14>; -C(=O)-R<15>; -CH=N-NH-C(=O)-R<16>; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; -C(=N-O-R<8>)-C1-4alkyl; R<7>; or -X3-R<7>; R<4> is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.
[WO03016306A1]