HIV inhibiting 6-substituted pyrimidines

1. A compound of formula

a pharmaceutically acceptable addition salt, or a stereochemically isomeric form thereof, wherein:

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

R 2 , R 3 , R 6 and R 7 independently are hydrogen; hydroxy; halo; C 3-7 cycloalkyl; C 1-6 alkyloxy; carboxyl; C 1-6 alkyloxycarbonyl; cyano; nitro; amino; mono- or di(C 1-6 alkyl)amino; polyhaloC 1-6 alkyl; polyhaloC 1-6 alkyloxy; —C(═O)R 9 ; C 1-6 alkyl optionally substituted with halo, cyano or —C(═O)R 9 ; C 2-6 alkenyl optionally substituted with halo, cyano or —C(═O)R 9 ; C 2-6 alkynyl optionally substituted with halo, cyano or —C(═O)R 9 ;

R 4 and R 8 independently are hydroxy; halo; C 3-7 cycloalkyl; C 1-6 alkyloxy; carboxyl; C 1-6 alkyloxycarbonyl; formyl; cyano; nitro; amino; mono- or di(C 1-6 alkyl)amino; polyhaloC 1-6 alkyl; polyhaloC 1-6 alkyloxy; —C(═O)R 9 ; —S(═O) r R 9 ; —NH—S(═O) 2 R 9 ; —NHC(═O)H; —C(═O)NHNH 2 ; —NHC(═O)R 9 ; Het; C 1-6 alkyl optionally substituted with halo, cyano, amino, mono- or di(C 1-6 alkyl)amino, —C(═O)—R 9 , Het or with C 1-6 alkyloxy; C 2-6 alkenyl optionally substituted with halo, cyano, amino, mono- or di(C 1-6 alkyl)amino, —C(═O)—R 9 , Het, or with C 1-6 alkyloxy; C 2-6 alkynyl optionally substituted with halo, cyano, amino, mono- or di(C 1-6 alkyl)amino, —C(═O)—R 9 , Het, or with C 1-6 alkyloxy;

R 5 is —CH 2 —O—P(═O)(OR 5g ) 2 ; —CH 2 —O—C(═O)—NH 2 ; —C(═O)—R 5d ;

each R 5d independently is aryl or Het;

each R 5g independently is C 1-6 alkyl;

each R 9 independently is C 1-6 alkyl, amino, mono- or di(C 1-6 alkyl)amino, or polyhalo-C 1-6 alkyl;

X is —NR 1 —, —O—, —CH 2 —, —S—;

each r independently is 1 or 2;

each Het independently is pyridyl, thienyl, furanyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, thiadiazolyl, oxadiazolyl, quinolinyl, benzothienyl, benzofuranyl; which each may optionally be substituted with one or two substituents each independently selected from C 1-6 alkyl, halo, hydroxy, cyano, C 1-6 alkyloxy, C 2-6 alkenyl substituted with halo, hydroxy or with cyano;

each aryl independently is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, mono or di(C 1-6 alkyl)amino C 1-6 alkyl, C 1-6 alkylcarbonyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, phenylC 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, aminosulfonyl, C 1-6 alkylthio, cyano, nitro, polyhaloC 1-6 alkyl, polyhaloC 1-6 alkyloxy, amino carbonyl, phenyl, and Het.

2. The compound of claim 1 wherein the compound of formula (I) is represented by formula

3. The compound of claim 1 , wherein R 1 is hydrogen.

4. The compound of claim 1 , wherein R 2 , R 3 , R 6 and R 7 independently are hydrogen; halo; C 1-6 alkyl; cyano.

5. The compound of claim 1 , wherein R 4 and R 8 independently are cyano; C 1-6 alkyl substituted with cyano; C 2-6 alkenyl substituted with cyano.

6. The compound of claim 1 , wherein R 8 is a radical —CH 2 —CH 2 —CN, —CH═CH—CN, or —C≡C—CN.

7. The compound of claim 6 , wherein R 8 is a radical —CH═CH—CN.

8. The compound of claim 1 , wherein R 4 is cyano.

9. The compound of claim 1 , wherein

R 5 is

—CH 2 —O—P(═O)(OR 5g ) 2 ; each R 5g is C 1-6 alkyl;

—CH 2 —O—C(═O)—NH 2 ; or

—C(═O)—R 5d ; wherein R 5d is thiazolyl.

10. The compound of claim 1 , wherein X is —NH—.

11. The compound of claim 1 , wherein each aryl independently is phenyl or phenyl substituted with one, two or three substituents each independently selected from halo, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy, cyano, nitro, trifluoromethyl.

12. A pharmaceutical composition comprising an effective amount of a compound of formula (I) as defined in claim 1 and a carrier.

13. The pharmaceutical composition of claim 12 , wherein

R 5 is

—CH 2 —O—P(═O)(OR 5g ) 2 ; each R 5g is C 1-6 alkyl;

—CH 2 —O—C(═O)—NH 2 ; or

—C(═O)—R 5d ; wherein R 5d is thiazolyl.

14. A pharmaceutical composition comprising an effective amount of a compound of formula (I) as defined in claim 2 and a carrier.