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Claims for Patent: 8,003,789

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Claims for Patent: 8,003,789

Title:HIV replication inhibiting pyrimidines
Abstract: This invention concerns the use of compounds of formula ##STR00001## the N-oxides, pharmaceutically acceptable addition salts, quaternary amines, stereochemically isomeric forms thereof, wherein -a.sup.1=a.sup.2-a.sup.3=a.sup.4- forms phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl with the attached vinyl group; n is 0 to 5; R.sup.1 is hydrogen, aryl, formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyl, C.sub.1-6alkyloxycarbonyl, substituted C.sub.1-6alkyl, substituted C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl; R.sup.2 is hydroxy, halo, optionally substituted C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6, 5-membered heterocyclic ring; L is optionally substituted C.sub.1-10alkyl, C.sub.2-10alkenyl, C.sub.2-10alkynyl or C.sub.3-7cycloalkyl; or --X--R.sup.3; Q is hydrogen, C.sub.1-6alkyl, halo, polyhalo-C.sub.1-6alkyl, optionally substituted amino group; Y represents hydroxy, halo, C.sub.3-7cycloalkyl, optionally substituted C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono-or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, 13 NHC(.dbd.O)R.sup.6,--C(.dbd.NH)R.sup.6, aryl; for the treatment of subjects suffering from HIV infection.
Inventor(s): De Corte; Bart (Southampton, PA), de Jonge; Marc Rene (Hontenissestraat, NL), Heeres; Jan (Vosselaar, BE), Ho; Chih Yung (Lansdale, PA), Janssen; Paul Adriaan Jan (Vosselaar, BE), Herwig Arts, legal representative; Frank Xavier Jozef (Brasschaat, BE), Kavash; Robert W. (Glenside, PA), Koymans; Lucien Maria Henricus (Retie, BE), Kukla; Michael Joseph (Maple Glen, PA), Ludovici; Donald William (Quakertown, PA), Van Aken; Koen Jeanne Alfons (Kuurne, BE), Marcel Andries; Koenraad Jozef Lodewijk (Beerse, BE)
Assignee: Janssen Pharmaceutica, N.V. (BE)
Application Number:11/930,835
Patent Claims: 1. A compound having the formula ##STR00032## a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4= represents a bivalent radical of formula --CH.dbd.CH--C(R.sup.2a).dbd.CH--CH.dbd. (b-1); q is 0, 1, 2; 3; or 4; R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylcarbonyloxy; C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl substituted with C.sub.1-6alkyloxycarbonyl; R.sup.2a is cyano, C.sub.1-6alkyl substituted with cyano, C.sub.2-6alkenyl substituted with cyano, or C.sub.2-6alkynyl substituted with cyano; each R.sup.2 independently is hydroxy, halo, C.sub.1-6alkyl optionally substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms or cyano, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms or cyano, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl) amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or a radical of formula ##STR00033## wherein each A independently is N, CH or CR.sup.6; B is NH, O, S or NR.sup.6; p is 1 or 2; and R.sup.6 is methyl, amino, mono- or dimethylamino or polyhalomethyl; L is C.sub.1-10alkyl, C.sub.2-10alkenyl, C.sub.2-10alkynyl, C.sub.3-7cycloalkyl, whereby each group may be substituted with one or two substituents independently selected from C.sub.3-7cycloalkyl, indolyl or isoindolyl, each optionally substituted with one, two, three or four substituents each independently selected from halo, C.sub.1-6alkyl, hydroxy, C.sub.1-6alkyloxy, cyano, amino-carbonyl, nitro, amino, polyhalomethyl, polyhalomethyloxy and C.sub.1-6alkylcarbonyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; or L is --X--R.sup.3 wherein R.sup.3 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each may optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; and X is --NR.sup.1--, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --CHOH--; Q represents hydrogen, C.sub.1-6alkyl, halo, polyhaloC.sub.1-6alkyl or --NR.sup.4R.sup.5; and R.sup.4 and R.sup.5 are each independently selected from hydrogen, hydroxy, C.sub.1-12alkyl, C.sub.1-12alkyloxy, C.sub.1-12alkylcarbonyl, C.sub.1-12alkyloxycarbonyl, aryl, amino, mono- or di(C.sub.1-12alkyl)amino, mono- or di(C.sub.1-12alkyl)aminocarbonyl wherein each of the aforementioned C.sub.1-12alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6 alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6, aryl and Het; or R.sup.4 and R.sup.5 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, azido; Y represents hydroxy, halo, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms, C.sub.1-6alkyl substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or aryl; aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, cyano, nitro, polyhaloC.sub.1-6alkyl and polyhaloC.sub.1-6alkyloxy; Het is an aliphatic or aromatic heterocyclic radical; said aliphatic heterocyclic radical is selected from pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl and tetrahydrothienyl wherein each of said aliphatic heterocyclic radical may optionally be substituted with an oxo group; and said aromatic heterocyclic radical is selected from pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl wherein each of said aromatic heterocyclic radical may optionally be substituted with hydroxy.

2. A compound as claimed in claim 1 wherein R.sup.1 is hydrogen; aryl; formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyl, C.sub.1-6alkyloxycarbonyl, or C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl.

3. A compound as claimed in claim 1 wherein R.sup.1 is hydrogen.

4. A compound as claimed in claim 1 wherein L is --X--R.sup.3 wherein R.sup.3 is 2,4,6-trisubstituted phenyl.

5. A compound as claimed in claim 1 wherein Y is cyano, --C(.dbd.O)NH.sub.2 or halo.

6. A compound according to claim 1 wherein Y is halogen.

7. A compound as claimed in claim 1 wherein Q is hydrogen or --NR.sup.4R.sup.5.

8. A compound as claimed in claim 1 wherein Q is --NR.sup.4R.sup.5.

9. A compound as claimed in claim 1 wherein the compound is 4-[[4-amino-5-chloro-6-[(2,4,6-trimethylphenyl)amino]-2-pyrimidinyl]amino- ]benzonitrile; 4-[[5-chloro-4-[(2,4,6-trimethylphenyl)amino]-2-pyrimidinyl]amino]benzoni- trile; 4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-2-pyrimidinyl]amino]ben- zonitrile; 4-[[4-amino-5-chloro-6-[(4-cyano-2,6-dimethylphenyl)amino]-2-py- rimidinyl]amino]benzonitrile; 4-[[5-bromo-6-[(4-cyano-2,6-dimethylphenyl)amino]-2-pyrimidinyl]amino]ben- zonitrile; or 4-[[4-amino-5-chloro-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amin- o]benzonitrile; a N-oxide, or an addition salt thereof.

10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically active amount of a compound having the formula ##STR00034## a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4= represents a bivalent radical of formula --CH.dbd.CH--C(R.sup.2a).dbd.CH--CH.dbd. (b-1); q is 0, 1, 2, 3 or 4; R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylcarbonyloxy; C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl substituted with C.sub.1-6alkyloxycarbonyl; R.sup.2a is cyano, C.sub.1-6alkyl substituted with cyano, C.sub.2-6alkenyl substituted with cyano, or C.sub.2-6alkynyl substituted with cyano; each R.sup.2 independently is hydroxy, halo, C.sub.1-6alkyl optionally substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms or cyano, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms or cyano, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or a radical of formula ##STR00035## wherein each A independently is N, CH or CR.sup.6; B is NH, O, S or NR.sup.6; p is 1 or 2; and R.sup.6 is methyl, amino, mono- or dimethylamino or polyhalomethyl; L is C.sub.1-10alkyl, C.sub.2-10alkenyl, C.sub.2-10alkynyl, C.sub.3-7cycloalkyl, whereby each group may be substituted with one or two substituents independently selected from C.sub.3-7cycloalkyl, indolyl or isoindolyl, each optionally substituted with one, two, three or four substituents each independently selected from halo, C.sub.1-6alkyl, hydroxy, C.sub.1-6alkyloxy, cyano, amino-carbonyl, nitro, amino, polyhalomethyl, polyhalomethyloxy and C.sub.1-6alkylcarbonyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each may optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; or L is --X--R.sup.3 wherein R.sup.3 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each may optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; and X is --NR.sup.1--, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --CHOH--; Q represents hydrogen, C.sub.1-6alkyl, halo, polyhaloC.sub.1-6alkyl or --NR.sup.4R.sup.5; and R.sup.4 and R.sup.5 are each independently selected from hydrogen, hydroxy, C.sub.1-12alkyl, C.sub.1-12alkyloxy, C.sub.1-12alkylcarbonyl, C.sub.1-12alkyloxycarbonyl, aryl, amino, mono- or di(C.sub.1-12alkyl)amino, mono- or di(C.sub.1-12alkyl)aminocarbonyl wherein each of the aforementioned C.sub.1-12alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6, aryl and Het; or R.sup.4 and R.sup.5 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, or azido; Y represents hydroxy, halo, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms, C.sub.1-6alkyl substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or aryl; aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, cyano, nitro, polyhaloC.sub.1-6alkyl and polyhaloC.sub.1-6alkyloxy; Het is an aliphatic or aromatic heterocyclic radical; said aliphatic heterocyclic radical is selected from pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl and tetrahydrothienyl wherein each of said aliphatic heterocyclic radical may optionally be substituted with an oxo group; and said aromatic heterocyclic radical is selected from pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl wherein each of said aromatic heterocyclic radical may optionally be substituted with hydroxy.

11. A process for preparing a compound as claimed in claim 1 comprising a) reacting an intermediate of formula (II) with an amino derivative of formula (III) under solvent-free conditions or in a reaction-inert solvent under a reaction-inert atmosphere ##STR00036## wherein W.sup.1 is a suitable leaving group and L, Y, Q, R.sup.1, R.sup.2, R.sup.2a, q and -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4=are as defined in claim 1; b) reacting an intermediate of formula (IV) with an intermediate of formula (V) under solvent-free conditions or in an appropriate solvent under a reaction-inert atmosphere ##STR00037## wherein W.sup.2 is a suitable leaving group and Y, Q, R.sup.1, R.sup.2, R.sup.2a, R.sup.3,q and -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4= are as defined in claim 1; c) reacting an intermediate of formula (IV) with an intermediate of formula (VI) in an appropriate solvent under a reaction-inert atmosphere in the presence of a suitable base ##STR00038## wherein W.sup.2 is a suitable leaving group and Y, Q, R.sup.1, R.sup.2, R.sup.2a, R.sup.3, q and -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4= are as defined in claim 1; or optionally converting the compound of formula (I-a), into an acid addition salt by treatment with an acid, or conversely, converting the acid addition salt form into the free base by treatment with alkali; or preparing stereochemically isomeric forms thereof to yield the desired compound of formula (I-a).

12. The combination of a compound having the formula ##STR00039## a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4= represents a bivalent radical of formula --CH.dbd.CH--C(R.sup.2a).dbd.CH--CH.dbd. (b-1); q is 0, 1, 2, 3, or 4; R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylcarbonyloxy; C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl substituted with C.sub.1-6alkyloxycarbonyl; R.sup.2a is cyano, C.sub.1-6alkyl substituted with cyano, C.sub.2-6alkenyl substituted with cyano, or C.sub.2-6alkynyl substituted with cyano; each R.sup.2 independently is hydroxy, halo, C.sub.1-6alkyl optionally substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms or cyano, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms or cyano, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl) amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or a radical of formula ##STR00040## wherein each A independently is N, CH or CR.sup.6; B is NH, O, S or NR.sup.6; p is 1 or 2; and R.sup.6 is methyl, amino, mono- or dimethylamino or polyhalomethyl; L is C.sub.1-10alkyl, C.sub.2-10alkenyl, C.sub.2-10alkynyl, C.sub.3-7cycloalkyl, whereby each group may be substituted with one or two substituents independently selected from C.sub.3-7cycloalkyl, indolyl or isoindolyl, each optionally substituted with one, two, three or four substituents each independently selected from halo, C.sub.1-6alkyl, hydroxy, C.sub.1-6alkyloxy, cyano, amino-carbonyl, nitro, amino, polyhalomethyl, polyhalomethyloxy and C.sub.1-6alkylcarbonyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each may optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; or L is --X--R.sup.3 wherein R.sup.3 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each may optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; and X is --NR.sup.1--, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --CHOH--; Q represents hydrogen, C.sub.1-6alkyl, halo, polyhaloC.sub.1-6alkyl or --NR.sup.4R.sup.5; and R.sup.4 and R.sup.5 are each independently selected from hydrogen, hydroxy, C.sub.1-12alkyl, C.sub.1-12alkyloxy, C.sub.1-12alkylcarbonyl, C.sub.1-12alkyloxycarbonyl, aryl, amino, mono- or di(C.sub.1-12alkyl)amino, mono- or di(C.sub.1-12alkyl)aminocarbonyl wherein each of the aforementioned C.sub.1-12alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6, aryl and Het; or R.sup.4 and R.sup.5 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, or azido; Y represents hydroxy, halo, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms, C.sub.1-6alkyl substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or aryl; aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, cyano, nitro, polyhaloC.sub.1-6alkyl and polyhaloC.sub.1-6alkyloxy; Het is an aliphatic or aromatic heterocyclic radical; said aliphatic heterocyclic radical is selected from pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl and tetrahydrothienyl wherein each of said aliphatic heterocyclic radical may optionally be substituted with an oxo group; and said aromatic heterocyclic radical is selected from pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl wherein each of said aromatic heterocyclic radical may optionally be substituted with hydroxy; and another antiretroviral compound.

13. A compound of formula ##STR00041## wherein -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4=represents a bivalent radical of formula --CH.dbd.CH--C(R.sup.2a).dbd.CH--CH.dbd. (b-1); q is 0, 1, 2, 3, or 4; R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylcarbonyloxy; C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl substituted with C.sub.1-6alkyloxycarbonyl; R.sup.2a is cyano, C.sub.1-6alkyl substituted with cyano, C.sub.2-6alkenyl substituted with cyano, or C.sub.2-6alkynyl substituted with cyano; each R.sup.2 independently is hydroxy, halo, C.sub.1-6alkyl optionally substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms or cyano, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms or cyano, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl) amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or a radical of formula ##STR00042## wherein each A independently is N, CH or CR.sup.6; B is NH, O, S or NR.sup.6; p is 1 or 2; and R.sup.6 is methyl, amino, mono- or dimethylamino or polyhalomethyl; Q represents hydrogen, C.sub.1-6alkyl, halo, polyhaloC.sub.1-6alkyl or --NR.sup.4R.sup.5; Y represents hydroxy, halo, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms, C.sub.1-6alkyl substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or aryl; R.sup.4 and R.sup.5 are each independently selected from hydrogen, hydroxy, C.sub.1-12alkyl, C.sub.1-12alkyloxy, C.sub.1-12alkylcarbonyl, C.sub.1-12alkyloxycarbonyl, aryl, amino, mono- or di(C.sub.1-12alkyl)amino, mono- or di(C.sub.1-12alkyl)aminocarbonyl wherein each of the aforementioned C.sub.1-12alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6, aryl and Het; or R.sup.4 and R.sup.5 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, or azido; aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, cyano, nitro, polyhaloC.sub.1-6alkyl and polyhaloC.sub.1-6alkyloxy; Het is an aliphatic or aromatic heterocyclic radical; said aliphatic heterocyclic radical is selected from pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl and tetrahydrothienyl wherein each of said aliphatic heterocyclic radical may optionally be substituted with an oxo group; and said aromatic heterocyclic radical is selected from pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl wherein each of said aromatic heterocyclic radical may optionally be substituted with hydroxy; and wherein W.sup.2 is a suitable leaving group.

14. A compound as claimed in claim 13 wherein the compound has the following formula ##STR00043##

15. A compound as claimed in claim 14 wherein the compound is 4-[[(5-bromo-4,6-dichloro)-2-pyrimidinyl]amino]-benzonitrile.

16. The compound of claim 13, wherein q is 0.

17. A method for treating HIV infection, comprising administering a compound having the formula ##STR00044## a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein -b.sup.1=b.sup.2-C(R.sup.2a)=b.sup.3-b.sup.4= represents a bivalent radical of formula --N.dbd.CH--C(R.sup.2a).dbd.CH--CH.dbd. (b-2); --CH.dbd.N--C(R.sup.2a).dbd.CH--CH.dbd. (b-3); --N.dbd.CH--C(R.sup.2a).dbd.N--CH.dbd. (b-4); --N.dbd.CH--C(R.sup.2a).dbd.CH--N.dbd. (b-5); q is 0, 1, 2 or 3; R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylcarbonyloxy; C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl substituted with C.sub.1-6alkyloxycarbonyl; R.sup.2a is cyano, C.sub.1-6alkyl substituted with cyano, C.sub.2-6alkenyl substituted with cyano, or C.sub.2-6alkynyl substituted with cyano; each R.sup.2 independently is hydroxy, halo, C.sub.1-6alkyl optionally substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms or cyano, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms or cyano, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl) amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or a radical of formula ##STR00045## wherein each A independently is N, CH or CR.sup.6; B is NH, O, S or NR.sup.6; p is 1 or 2; and R.sup.6 is methyl, amino, mono- or dimethylamino or polyhalomethyl; L is C.sub.1-10alkyl, C.sub.2-10alkenyl, C.sub.2-10alkynyl, C.sub.3-7cycloalkyl, whereby each group may be substituted with one or two substituents independently selected from C.sub.3-7cycloalkyl, indolyl or isoindolyl, each optionally substituted with one, two, three or four substituents each independently selected from halo, C.sub.1-6alkyl, hydroxy, C.sub.1-6alkyloxy, cyano, amino-carbonyl, nitro, amino, polyhalomethyl, polyhalomethyloxy and C.sub.1-6alkylcarbonyl, phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each may optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; or L is --X--R.sup.3 wherein R.sup.3 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each may optionally be substituted with one, two, three, four or five substituents each independently selected from the substituents defined in R.sup.2; and X is --NR.sup.1--, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --CHOH--; Q represents hydrogen, C.sub.1-6alkyl, halo, polyhaloC.sub.1-6alkyl or --NR.sup.4R.sup.5; and R.sup.4 and R.sup.5 are each independently selected from hydrogen, hydroxy, C.sub.1-12alkyl, C.sub.1-12alkyloxy, C.sub.1-12alkylcarbonyl, C.sub.1-12alkyloxycarbonyl, aryl, amino, mono- or di(C.sub.1-12alkyl)amino, mono- or di(C.sub.1-12alkyl)aminocarbonyl wherein each of the aforementioned C.sub.1-12alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6, aryl and Het; or R.sup.4 and R.sup.5 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, or azido; Y represents hydroxy, halo, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms, C.sub.1-6alkyl substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or aryl; aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, cyano, nitro, polyhaloC.sub.1-6alkyl and polyhaloC.sub.1-6alkyloxy; Het is an aliphatic or aromatic heterocyclic radical; said aliphatic heterocyclic radical is selected from pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl and tetrahydrothienyl wherein each of said aliphatic heterocyclic radical may optionally be substituted with an oxo group; and said aromatic heterocyclic radical is selected from pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl wherein each of said aromatic heterocyclic radical may optionally be substituted with hydroxy.

18. A compound as claimed in claim 1 wherein q is 0.

19. A compound as claimed in claim 1 wherein R.sup.2a is cyano.
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