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1. WO2004062613 - INHIBITEURS D'INTEGRASE HIV

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

CLAIMS

1. A compound having the formula


wherein:

R1 is -C1-C6 alkyl, C3-C6 cycloalkyl, -aryl, -C1-C6 alkyl-aryl, or -C1-C6 alkyl-diaryl;

R2 is -H, -OH, -C1-C6 alkyl unsubstituted or substituted with 1-3 R3, or -O R4;

Each R3 is independently selected from the group consisting of -H, -halo, -CN, -C1-C2 perfluoroalkyl, -C1-C6 alkyl, -C1-C2 perfluoroalkoxy, and -C1-C6 alkoxy;

R4 is -C1-C6 alkyl or -C3-C6 cycloalkyl;

B is selected from the group consisting of


and
;

R5 is -NR7R8; or Het wherein the bond attaching R5 is made to a heteroatom in said Het;

R6 is -H, -C1-C6 alkyl unsubstituted or substituted with 1-3 R3; and

R7 and R8 are independently -H or -C1-C6 alkyl;

or pharmaceutically acceptable enantiomer, diastereomer, salt, solvate or prodrug thereof.

2. The compound of claim 1 wherein the aryl is substituted with 1-3 R3.

3. The compound of claim 1 wherein R1 is -aryl, -C1-C6 alkyl-aryl, or -C1-C6 alkyl diaryl.

4. The compound of claim 3 wherein R1 is -aryl, -C1-C6 alkyl-phenyl, or -C1-C6 alkyl-diphenyl.

5. The compound of claim 4 wherein the aryl is selected from the group consisting of phenyl, naphthyl, furanyl, thienyl, indolyl, and benzimidazolyl, and aryl and phenyl are unsubstituted or substituted with 1-3 R3.

6. A compound of claim 4 wherein R1 is aryl selected from the group

consisting of naphthyl, 2-methyl-5 -furanyl, 2-thienyl, 3-indolyl, and

2-benzimidazolyl.

7. A compound of claim 4 wherein R1 is phenyl unsubstituted or substituted with 1-3 R3.

8. A compound of claim 7 wherein R1 is 3 -fluorophenyl, 4-fluorophenyl, 2,4-difiourophenyl, 3,4-diflourophenyl, 3-methyl-4-fluorophenyl, 3-chloro-4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3-methylphenyl, 4-methylphenyl, or 3,4-dimethylphenyl.

9. A compound of claim 1 where R2 is -H, methyl, -OH, or methoxy.

10. A compound of claim 9 where R2 is -H.

11. A compound of claim 1 wherein R6 is -C1-C6 alkyl.

12. A compound of claim 11 wherein R6 is methyl.

13. A compound of claim 1 wherein R5 is heteroaryl.

14. A compound of claim 13 wherein R5 is selected from the group consisting of fluorooxindole and methyltriazole.

15. A compound of claim 1 wherein R5 is a 4 to 7 membered monocylic heterocycle.

16. A compound of claim 15 wherein R5 is selected from the group consisting

of [1,2]thiazinane 1,1-dioxide and
, wherein X is a bond, O, S, NH, N-methyl, N-propyl, N-acetyl, N-(2-hydroxyethyl), N-pyridinyl, N-pyrazinyl, N-SO2Me, CH2, and CHOH.

17. A compound of claim 1 selected from the group consisting of

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3,4-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(4-chlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3-chlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[3-(4-fluorophenyl)propyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[3-(3,4-dichlorophenyl)propyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-N-[(4-methylphenyl)methyl]-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-N-[(3-methylphenyl)methyl]-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide; 1,6-dihydro-5-hydroxy-N-[(4-methoxyphenyl)methyl]-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-N-[(3-methoxyphenyl)methyl]-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3,5-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3-fluoro-4-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3,4-difluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide; N-[2-(4-fluorophenyl)ethyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(2,4-difluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3-chloro-4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3,4-dimethylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-1-methyl-6-oxo-N-(1-phenylethyl)-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(4-morpholinyl)-6-oxo-4-pyrimidinecarboxamide;

N-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[2-(3-fluorophenyl)ethyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(2,4-dimethoxyphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-N-[(5-methyl-2-furanyl)methyl]-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-N-[(2-methoxyphenyl)methyl]-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-(2,2-diphenylethyl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[2-(4-chlorophenyl)ethyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-N-[2-(4-methoxyphenyl)ethyl]-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(2-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-N-[[3-(trifluoromethyl)phenyl]methyl]-4-pyrimidinecarboxamide;

N-[2-(3-chlorophenyl)ethyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-N-(2-phenylethyl)-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-N-[(1S)-1-phenylethyl]-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-N-[[4-(trifluoromethyl)phenyl]methyl]-4-pyrimidinecarboxamide;

N-[1-(4-fluorophenyl)ethyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-(2-furanylmethyl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-N-(2-thienylmethyl)-4-pyrimidinecarboxamide;

N-(1,2-diphenylethyl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-N-(phenylmethyl)-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(2-chlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-N-[(2-methylphenyl)methyl]-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide; 1,6-dihydro-5-hydroxy-N-[2-(2-methoxyphenyl)ethyl]-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-N-[2-(3-methoxyphenyl)ethyl]-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-1-methyl-N-[2-(4-methylphenyl)ethyl]-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-N-[(3,4,5-trimethoxyphenyl)methyl]-4-pyrimidinecarboxamide;

N-[(2,5-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide; 1,6-dihydro-5-hydroxy-N-[(1R,2S)-2-hydroxy-1,2-diphenylethyl]-1-methyl- 6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(2,4-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(2,5-difluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide; 1 ,6-dilιydro-5-hydroxy- 1 -methyl-6-oxo-2-(tetrahydro- 1 , 1 -dioxido-2H- 1 ,2-thiazin-2-yl)-N-[[2-(trifluoromethyl)phenyl]methyl]-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-N-(1-phenylpropyl)-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

4-pyrimidinecarboxamide, N-[1-(4-chlorophenyl)ethyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(3,5-difluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-N-[[3-(trifluoromethoxy)phenyl]methyl]-4-pyrimidinecarboxamide;

1,6-dihydro-5-hydroxy-1-methyl-N-[1-(1-naphthalenyl)ethyl]-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[1-(4-bromophenyl)ethyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-1-methyl-N-[1-(2-naphthalenyl)ethyl]-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-1-methyl-N-[1-(4-methylphenyl)ethyl]-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-N-[1-(3-methoxyphenyl)ethyl]-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide; 1,6-dihydro-5-hydroxy-N-[1-(4-methoxyphenyl)ethyl]-1-methyl-6-oxo-2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1 , 6-dihydro-5-hydroxy-N-[2-(1H-indol-3-yl)ethyl]-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

1,6-dilιydro-5-hydroxy-1-methyl-6-oxo-N-[(1S)-1-phenylpropyl]-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-(1H-benzimidazol-2-ylmethyl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(3-methyl-1H-1,2,4-triazol-1-yl)-6-oxo-4-pyrimidinecarboxamide;

N-[(3,4-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(3-methyl-1H-1,2,4-triazol-1-yl)-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(3-methyl-1H-1,2,4-triazol-1-yl)-6-oxo-4-pyrimidinecarboxamide;

N-[(3,4-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(4-morpholinyl)-6-oxo-4-pyrimidinecarboxamide;

N-[(3-fluoro-4-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(4-morpholinyl)-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(4-morpholinyl)-6-oxo-4-pyrimidinecarboxamide;

N-[(3-chloro-4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(4-morpholinyl)-6-oxo-4-pyrimidinecarboxamide;

N-[(3,4-dimethylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(4-morpholinyl)-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(5-methyl- 1 H-1,2,4-triazol-1-yl)-6-oxo-4-pyrimidinecarboxamide;

N-[(3,4-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(5-methyl-1H-1,2,4-triazol-1-yl)-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-methyl-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-methyl-6-oxo-4-pyrimidinecarboxamide;

2-(4-acetyl-1-piperazinyl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;

2-(4-acetyl-1-piperazinyl)-N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro- 5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(4-propyl-1-piperazinyl)-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(4-propyl-1-piperazinyl)-4-ρyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-piperazinyl)- 4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-piperazinyl)- 4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-2-(4-hydroxy-1-piperidinyl)-1-methyl-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-2-(4-hydroxy-1-piperidinyl)-1-methyl-6-oxo-4-pyrimidinecarboxamide;

2-(6-fluoro-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[4-(2-pyridinyl)-1-piperazinyl]-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[4-(2-pyridinyl)-1-piperazinyl]-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[4-(2-pyrimidinyl)-1-piperazinyl]-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[4-(2-pyrimidinyl)-1-piperazinyl]-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[4-(methylsulfonyl)-1-piperazinyl]-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[4-(methylsulfonyl)-1-piperazinyl]-6-oxo-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-pyrrolidinyl)-4-pyrimidinecarboxamide;

N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[2-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)ethyl]-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[3-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)propyl]-4-pyrimidinecarboxamide;

N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)ethyl]-4-pyrimidinecarboxaιnide; and

N-[(3,4-dichlorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-[2- (tetrahydro-1,1-dioxido-2H-1,2-thiazin-2-yl)ethyl]-4-pyrimidinecarboxamide.

18. A compound having the formula


wherein,

n is 1 to 4;

R5 is Het wherein the bond attaching R5 is made to a heteroatom in said Het;

R9 and R10 are each independently H, halo, C1-6 alkyl, C1-6 alkoxy or CF3; and

R11 is C1-6 alkyl;

or a pharmaceutically acceptable enantiomer, diastereomer, salt, solvate or prodrug thereof.

19. The compound of claim 18 wherein R5 is a C4-7 monocyclic heterocycle.

20. The compound of claim 19 wherein the heterocycle is substituted with at least one of C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 alkyl carbonyl, C6-10 aryl, C7-14 alkyl, aryl, C1-6 alkylsulfonyl, C6-10 arylsulfonyl, C1-6 alkylurea, C3-7

cycloalkylurea, carbonyl, carboxamide or hydroxyl.

21. The compound of claim 18 having one of the following structures;










22. A compound having the formula:


wherein n is 1 to 4;

R9 and R10 are each independently H, halo, C1-6 alkyl, C1-6 alkoxy or CF3;

X is C, O or N;

R11 is C1-6 alkyl; and

R12 is H, d-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 alkyl carbonyl, C6-10 aryl, C7- 14 alkyl; aryl, C1-6 alkylsulfonyl, C6-10 arylsulfonyl, C1-6 alkylurea, C3-7 cycloalkylurea, carbonyl, carboxamide or hydroxyl;

said R12 being present only when X is C or N;

or a pharmaceutically acceptable enantiomer, diastereomer, salt, solvate or prodrug thereof.

23. The compound of claim 22 wherein m is 1.

24. The compound of claim 22 wherein R9 is halo.

25. The compound of claim 24 wherein R9 is fluoro or chloro.

26. The compound of claim 24 wherein R10 is methyl.

27. The compound of claim 25 wherein R10 is chloro.

28. The compound of claim 22 wherein R9 is methyl.

29. The compound of claim 22 wherein R9 and R10 are not both H.

30. The compound of claim 22 wherein X is O.

31. The compound of claim 22 wherein X is N.

32. A composition comprising the compound of Claim 1 and a

pharmaceutically acceptable carrier.

33. The composition according to Claim 32 further comprising a compound having anti-HIV activity.

34. The composition according to Claim 33 wherein the compound having anti-HIV activity is effective to inhibit the function of a target selected from the group consisting of HIV protease, a nucleoside reverse transcriptase, a non-nucleoside reverse transcriptase or HIV entry.

35. The composition of claim 33 wherein the compound having anti-HIV activity is selected from:

(a) an HIV protease inhibitor,

(b) a nucleoside reverse transcriptase inhibitor,

(c) a non-nucleoside reverse transcriptase inhibitor,

(d) an HlV-entry inhibitor, and

(e) an immunomodulator,

or combination thereof.

36. A method of inhibiting the function of the HIV integrase

comprising contacting the HIV integrase with the compound of Claim 1.

37. A method of treating an HIV infection in a patient, comprising

administering to the patient a therapeutically effective amount of the compound of Claim 1, or a pharmaceutically acceptable enantiomer, diastereomer, solvate, prodrug or salt thereof.

38. The method according to Claim 37 wherein the compound is effective to inhibit the function of the HIV integrase.

39. The method according to Claim 37 further comprising administering another compound having anti-HIV activity prior to, after or simultaneously with the compound of Claim 1.

40. The method according to Claim 39 wherein the compound having anti-HIV activity is effective to inhibit the function of a target selected from the group consisting of HIV protease, a nucleoside reverse transcriptase, a non-nucleoside reverse transcriptase or HIV entry.

41. The method according to Claim 39 wherein the other compound having anti-HIV activity is effective to inhibit the function of target in the HIV life cycle other than the HIV integrase.

42. Use of the compound of Claim 1 for the manufacture of a medicament for treating HIV infection in a patient.

43. Use of the composition of Claim 32 for the manufacture of a medicament for treating HIV infection in a patient.

44. A compound of the formula:


wherein;

n is 0, 1 or 2;

R13 is -H, -C1-6 alkyl, C1-6 cycloalkyl, -aryl, C1-6 alkyl-cycloalkyl, -C1-6 alkyl-aryl, or -C1-6 alkyl-diaryl,

R14 is -H, -C1-6 alkyl, C1-6 cycloalkyl, -aryl, C1-6 alkyl-aryl, or -C1-6 alkyl-diaryl,

R15 is -H, -C1-6 alkyl, C1-6 alkyl-cycloalkyl, -aryl, or -C1-6 alkyl-aryl, and

R16 is -H, -C1-C6 alkyl, C1-6 cycloalkyl, -aryl, C1-6 alkyl-aryl, or -C1-6 alkyl-diaryl.