HIV inhibiting 5-substituted pyrimidines

1. A compound of formula

a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein

A is —CH 2 —CH 2 —, —CH═CH—, —C≡C—;

each R 1 independently is hydrogen, aryl, formyl, C 1-6 alkylcarbonyl, C 1-6 alkyl, C 1-6 alkyloxycarbonyl;

R 2 is hydroxy, halo, C 1-6 alkyl, carboxyl, cyano, —C(═O)R 6 , nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl;

X 1 is —NR 1 —, —O—, —S—, —S(═O) p —;

R 3 is H, C 1-6 alkyl, halo;

R 4 is H, C 1-6 alkyl, halo;

R 5 is nitro, amino, mono- and diC 1-4 alkylamino, halo, —CO—H, —CO—R 6 , —COOR 7 , —NH—C(═O)H, —CH═N—O—R 8 ;

R 6 is C 1-4 alkyl, amino, mono(C 1-4 alkyl)amino or polyhaloC 1-4 alkyl;

R 7 is hydrogen, arylC 1-6 alkyl;

R 8 is hydrogen, C 1-6 alkyl, aryl;

each p is 1 or 2;

each aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, mono or di(C 1-6 alkyl)aminoC 1-6 alkyl, C 1-6 alkylcarbonyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, C 1-6 alkylthio, cyano, nitro, polyhaloC 1-6 alkyl, polyhaloC 1-6 alkyloxy, aminocarbonyl.

2. A compound according to claim 1 wherein

A is —CH 2 —CH 2 — or —CH═CH—;

R 1 is hydrogen or C 1-6 alkyl;

R 2 is cyano or aminocarbonyl;

X 1 is —NR 1 —, —O—;

R 3 is H, C 1-6 alkyl, halo;

R 4 is H, C 1-6 alkyl, halo.

3. A compound according to claim 1 wherein

R 6 is C 1-4 alkyl, amino, or mono(C 1-4 alkyl)amino;

R 7 is hydrogen;

R 8 is hydrogen, C 1-4 alkyl;

aryl is phenyl or phenyl substituted with one, two or three substituents each independently selected from halo, hydroxy, mercapto, C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, mono or di(C 1-6 alkyl)aminoC 1-6 alkyl, C 1-6 alkylcarbonyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, C 1-6 alkylthio, cyano, nitro, polyhaloC 1-6 alkyl, polyhaloC 1-6 alkyloxy, aminocarbonyl.

4. A compound according to claim 1 wherein

A is —CH 2 —CH 2 — or —CH═CH—;

R 1 is hydrogen;

R 2 is cyano;

X 1 is —NH— or —O—;

R 3 is H, C 1-4 alkyl, halo;

R 4 is H, C 1-4 alkyl, halo.

5. A compound according to claim 1 wherein

R 6 is C 1-4 alkyl, or amino;

R 7 is hydrogen;

R 8 is hydrogen, C 1-4 alkyl;

aryl is phenyl or phenyl substituted with one, two or three substituents each independently selected from halo, hydroxy, C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, mono or di(C 1-6 alkyl)aminoC 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, C 1-6 alkylthio, cyano, nitro, trifluoromethyl, trifluoromethoxy, aminocarbonyl.

6. A compound according to claim 1 wherein A is —CH═CH—; X 1 is —NH—;

R 3 is methyl or halo; R 4 is methyl or halo; R 6 is amino.

7. A compound according to claim 1 wherein

R 5 is nitro; or

R 5 is amino; mono- and di C 1-4 alkylamino; —NH—C(═O)H.

8. A compound according to claim 1 wherein

R 5 is halo.

9. A compound according to claim 1 wherein

R 5 is —CO—H, —CO—R 6 , —COOR 7 .

10. A compound according to claim 1 wherein

R 5 is —CH═N—O—R 8 .

11. A compound according to claim 1 , wherein R 5 is amino or mono- and di-C 1-4 alkylamino.

12. A compound according to claim 1 , wherein R 8 is hydrogen or C 1-4 alkyl.

13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound as claimed in claim 1 .

14. A process for preparing a pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound as claimed in claim 1 characterized in that a therapeutically effective amount of a compound as claimed in claim 1 is intimately mixed with a pharmaceutically acceptable carrier.

15. A method for treating HIV infection comprising:

administering a compound according to claim 1 to a patient in need thereof.