Claims for Patent: 7,820,660
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Summary for Patent: 7,820,660
Title: | N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase |
Abstract: | N-substituted 5-hydroxypyrimidin-6-one-4-carboxamides of formula: ##STR00001## are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described. |
Inventor(s): | Crescenzi; Benedetta (Rome, IT), Gardelli; Cristina (Ariccia, IT), Muraglia; Ester (Rome, IT), Nizi; Emanuela (Siena, IT), Orvieto; Federica (Rome, IT), Pace; Paola (Rome, IT), Pescatore; Giovanna (Cosenza, IT), Petrocchi; Alessia (Rome, IT), Poma; Marco (Grosseto, IT), Rowley; Michael (Axa, IT), Scarpelli; Rita (Rome, IT), Summa; Vincenzo (Velletri, IT) |
Assignee: | Instituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A. (Rome, IT) |
Application Number: | 12/214,595 |
Patent Claims: |
1. A combination which comprises: (i) a compound selected from the group consisting of N-(2-ethoxybenzyl)-5-hydroxy-1-methyl-2-(4-methylphenyl)-6-oxo-1,6-dihydr-
opyrimidine-4-carboxamide; N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-2-(4-methylphenyl)-6-oxo-1,6-d- ihydropyrimidine-4-carboxamide; N-(2,3-dimethoxybenzyl)-2-{4-[(dimethylamino)methyl]phenyl}-5-hydroxy-1-m-
ethyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-2-{4-[(dimethylamino)methyl]phenyl}-5-hydroxy-1-methyl- -6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-6-oxo-2-[4-(pyrrolidin-1-ylmet-
hyl)phenyl]-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[4-(pyrrolidin-1-ylmethyl)p- henyl]-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[4-(piperidin-1-ylmethyl)ph-
enyl]-1,6-dihydropyrimidine-4-carboxamide; N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-2-[4-(morpholin-4-ylmethyl)phe- nyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-[4-(morpholin-4-ylmethyl)phenyl]--
6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{4-[(4-methylpiperazin-1-yl)methy- l]phenyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{4-[(diethylamino)methyl]phenyl}-N-(2,3-dimethoxybenzyl)-5-hydroxy-1-me-
thyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{4-[(diethylamino)methyl]phenyl}-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-- 6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(dimethylamino)(phenyl)methyl]-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-
-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-2-[(4-formylpiperazin-1-yl)(phenyl)methyl]-5-hydroxy-1- -methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-{phenyl[(pyridin-3-ylmethyl-
)amino]methyl}-1,6-dihydropyrimidine-4-carboxamide; 2-benzyl-1-[2-(dimethylamino)ethyl]-N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1,- 6-dihydropyrimidine-4-carboxamide; 1-[2-(dimethylamino)ethyl]-N-(4-fluorobenzyl)-5-hydroxy-2-(2-methylphenyl-
)-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylphenyl)-6-oxo-1,6-dihydr- opyrimidine-4-carboxamide; 2-benzyl-N-(2,3-dimethoxybenzyl)-1-[2-(dimethylamino)ethyl]-5-hydroxy-6-o-
xo-1,6-dihydropyrimidine-4-carboxamide; 2-{4-[(4-ethylpiperazin-1-yl)methyl]phenyl}-N-(4-fluorobenzyl)-5-hydroxy-- 1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-{4-[(2-pyridin-3-ylpiperidi-
n-1-yl)methyl]phenyl}-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carbo- xamide; N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimi- dine-4-carboxamide;
N-[4-fluoro-2-(trifluoromethyl)benzyl]-5-hydroxy-1-methyl-6-oxo-1,6-dihyd- ropyrimidine-4-carboxamide; N-(3-chloro-4-methylbenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin- e-4-carboxamide;
5-hydroxy-N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]1-methyl-2-{4-[(- 4-methylpiperazin-1-yl)methyl]phenyl}-6-oxo-1,6-dihydropyrimidine-4-carbox- amide; N-(4-fluorobenzyl)-5-hydroxy-2-(4-{[(2R)-2-(methoxymethyl)pyrrolidi-
n-1-yl]methyl}phenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-(4-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl- ]methyl}phenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-2-(4-{[(4-fluorobenzyl)amino]methyl}phenyl)-5-hydroxy-- 1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-benzyl-N-(4-fluorobenzyl)-5-hydroxy-1-(2-morpholin-4-ylethyl)-6-oxo-1,6- -dihydropyrimidine-4-carboxamide;
1-[2-(dimethylamino)ethyl]-N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1,6-dihydro- pyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1-(pyridin-3-ylmethyl)-1,6-dihydropyri- midine-4-carboxamide;
2-benzyl-N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1-(2-pyrrolidin-1-ylethyl)-1,- 6-dihydropyrimidine-4-carboxamide; 2-benzyl-N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1-(2-piperidin-1-ylethyl)-1,6- -dihydropyrimidine-4-carboxamide;
2-(1-benzylpiperidin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,- 6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methylpiperidin-2-yl)-6-oxo-1,- 6-dihydropyrimidine-4-carboxamide;
2-(1-benzylpiperidin-3-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,- 6-dihydropyrimidine-4-carboxamide; 1-{3-[(dimethylamino)methyl]benzyl}-N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1,- 6-dihydropyrimidine-4-carboxamide;
N-(2,3-dimethoxybenzyl)-1-[2-(dimethylamino)ethyl]-5-hydroxy-6-oxo-1,6-di- hydropyrimidine-4-carboxamide; N-(2,3-dimethoxybenzyl)-5-hydroxy-6-oxo-1-(pyridin-3-ylmethyl)-1,6-dihydr- opyrimidine-4-carboxamide;
N4-(4-fluorobenzyl)-5-hydroxy-1-methyl-N2-(2-morpholin-4-ylethyl)-6-oxo-1- ,6-dihydropyrimidine-2,4-dicarboxamide; N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1-[3-(pyrrolidin-1-ylmethyl)benzyl]1,6- -dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-[3-(morpholin-4-ylmethyl)benzyl]-6-oxo-1,6- -dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-{3-[(4-methylpiperazin-1-yl)methyl]benzyl}- -6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1-{3-[(4-pyridin-2-ylpiperazin-1-yl)me- thyl]benzyl}-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-[2-(morpholin-4-ylmethyl)benzyl]-6-oxo-1,6- -dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1-{2-[(4-pyridin-2-ylpiperazin-1-yl)me- thyl]benzyl}-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-pyrrolidin-2-yl-1,6-dihydro- pyrimidine-4-carboxamide;
N4-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-N2-(pyridin-2-ylmethyl)-1,6-- dihydropyrimidine-2,4-dicarboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-(2-hydroxy-3-morpholin-4-ylpropyl)-6-oxo-1- ,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-[4-(morpholin-4-ylmethyl)benzyl]-6-oxo-1,6- -dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(2-morpholin-4-ylethyl)-6-oxo-1,6- -dihydropyrimidine-4-carboxamide;
2-(2,2-dimethoxyethyl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-di- hydropyrimidine-4-carboxamide; 2-(2,3-dihydro-1H-indol-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo- -1,6-dihydropyrimidine-4-carboxamide;
2-[2-(4-benzoylpiperazin-1-yl)ethyl]-N-(4-fluorobenzyl)-5-hydroxy-1-methy- l-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[1-(N,N-dimethylglycyl)piperidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-m- ethyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-2,3-dihydro-1H-indol-2-- yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-(1,2,3,4-tetrahydroquinolin- -2-yl)-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1,2,3,4-tetrahydroquino- lin-2-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide; tert-butyl(2S,4R)-4-(benzyloxy)-2-(4-{[(4-fluorobenzyl)amino]carbonyl}-5--
hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)pyrrolidine-1-carboxylate- ; tert-butyl(2S,4R)-2-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-met- hyl-6-oxo-1,6-dihydropyrimidin-2-yl)-4-hydroxypyrrolidine-1-carboxylate;
2-[(2S,4R)-4-(benzyloxy)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-m- ethyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-[(2S,4R)-4-hydroxypyrrolidin-2-yl]-1-methy- l-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-2-[(2S,4R)-4-hydroxy-1-methylpyrrolidin-2-yl- ]-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S,4R)-4-(benzyloxy)-1-methylpyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hy-
droxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S,4R)-1-benzoyl-4-(benzyloxy)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-h- ydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[1-(N,N-dimethylglycyl)-2,3-dihydro-1H-indol-2-yl]-N-(4-fluorobenzyl)-5- -hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(1-benzoyl-2,3-dihydro-1H-indol-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-me-
thyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridin-2-ylcarbonyl)-2- ,3-dihydro-1H-indol-2-yl]-1,6-dihydropyrimidine-4-carboxamide; tert-butyl
3-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-oxo-1,6-dihyd- ropyrimidin-2-yl)-4-methylpiperazine-1-carboxylate; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,- 6-dihydropyrimidine-4-carboxamide;
(+)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-ox- o-1,6-dihydropyrimidine-4-carboxamide (-)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-ox- o-1,6-dihydropyrimidine-4-carboxamide
2-(1-ethyl-2,3-dihydro-1H-indol-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-meth- yl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(1-benzoylpiperidin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1- ,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridin-2-ylcarbonyl)pi- peridin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(2-methyl-1,2,3,4-tetrahydroisoqu-
inolin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(1-benzoylpyrrolidin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-- 1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridin-2-ylcarbonyl)py-
rrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methylpyrrolidin-2-yl)-6-oxo-1- ,6-dihydropyrimidine-4-carboxamide; 2-[(2S,4R)-4-(benzyloxy)-1-(pyridin-2-ylcarbonyl)pyrrolidin-2-yl]-N-(4-fl-
uorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[1-(dimethylamino)-2-phenylethyl]-N-(4-fluorobenzyl)-5-hydroxy-1-methyl- -6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[(2S,4R)-1-benzoyl-4-hydroxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydro- xy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-(1-isobutyl-2,3-dihydro-1H-indol-2-yl)-1-m- ethyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-(1-isopropyl-2,3-dihydro-1H-indol-2-yl)-1-- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[1-(N,N-dimethylglycyl)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-{1-[(6-bromopyridin-2-yl)carbonyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)-5- -hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methylpiperazin-2-yl)-6-oxo-1,- 6-dihydropyrimidine-4-carboxamide;
2-(1-benzoyl-4-methylpiperazin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methy- l-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridin-2-ylcarbonyl)-1-
,2,3,4-tetrahydroquinolin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; 2-(1-acetylpyrrolidin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1- ,6-dihydropyrimidine-4-carboxamide;
2-[1-(cyclopropylcarbonyl)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1- -methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-[1-(methylsulfonyl)pyrrolidin-2-y- l]-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-[(4-methylmorpholin-3-yl)carbo- nyl]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(1,4-dimethylpiperazin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-ox- o-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridin-3-ylcarbonyl)py- rrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S,4R)-1-acetyl-4-(benzyloxy)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hy-
droxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-(1-isonicotinoylpyrrolidin-2-yl)-1-methyl-- 6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{1-[(ethylamino)carbonyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)-5-hydroxy--
1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-[(1-methyl-1H-imidazol-2-yl)ca- rbonyl]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[(2S,4R)-1-acetyl-4-hydroxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydrox- y-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[1-(anilinocarbonyl)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-met- hyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-(4-ethyl-1-methylpiperazin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-- 6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-[(1-oxidopyridin-2-yl)carbonyl- ]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyrazin-2-ylcarbonyl)py- rrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; 2-[(4R)-3-acetyl-1,3-thiazolidin-4-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-met- hyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-[1-methyl-4-(methylsulfonyl)piper- azin-2-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylthiomorpholin-3-yl)-6-ox- o-1,6-dihydropyrimidine-4-carboxamide;
N-[4-fluoro-2-(methylsulfonyl)benzyl]-5-hydroxy-1-methyl-6-oxo-2-[1-(pyra- zin-2-ylcarbonyl)pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; 2-(1-acetylpyrrolidin-2-yl)-N-[4-fluoro-2-(methylsulfonyl)benzyl]-5-hydro-
xy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(3-acetyl-1,3-thiazolidin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6- -oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[1-(acetylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-
-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(1-acetylpyrrolidin-2-yl)-N-(2-ethoxybenzyl)-5-hydroxy-1-methyl-6-oxo-1- ,6-dihydropyrimidine-4-carboxamide; 2-(4-acetyl-1-methylpiperazin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-
-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-[1-methyl-4-(pyrazin-2-ylcarbonyl- )piperazin-2-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-(1-acetylpyrrolidin-2-yl)-5-hydroxy-1-methyl-N-[2-(methylthio)benzyl]-6- -oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-{1-[(1H-imidazol-5-ylcarbonyl)amino]-1-met- hylethyl}-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[1-benzoyl-4-(pyrazin-2-ylcarbonyl)piperazin-2-yl]-N-(4-fluorobenzyl)-5- -hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(4-benzoyl-1-methylpiperazin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methy-
l-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[4-(benzyloxy)-1-(pyrazin-2-ylcarbonyl)pyrrolidin-2-yl]-N-(4-fluorobenz- yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-(1-acetylpyrrolidin-2-yl)-N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-6-- oxo-1,6-dihydropyrimidine-4-carboxamide; 2-(1-acetylpyrrolidin-2-yl)-5-hydroxy-N-(2-methoxybenzyl)-1-methyl-6-oxo-- 1,6-dihydropyrimidine-4-carboxamide;
N1-[1-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-oxo-1,6-d- ihydropyrimidin-2-yl)-1-methylethyl]-N2,N2-dimethylethanediamide; 2-(1-acetylpyrrolidin-2-yl)-N-[2-(dimethylamino)benzyl]-5-hydroxy-1-methy-
l-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S)-1-acetylpyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-- oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-2-[4-hydroxy-1-(pyrazin-2-ylcarbonyl)pyrroli- din-2-yl]-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-[1-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-oxo-1,6-di- hydropyrimidin-2-yl)-1-methylethyl]imidazo[2,1-b][1,3]thiazole-6-carboxami- de; 2-[(2S,4S)-1-acetyl-4-fluoropyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydr- oxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-methyl-4-[(1-methyl-1H-imidazo- l-2-yl)carbonyl]piperazin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxa- diazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamid- e; N1-{1-[4-({[4-fluoro-2-(methylsulfonyl)benzyl]amino}carbonyl)-5-hydroxy- -1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl]-1-methylethyl}-N2,N2-dimethylet- hanediamide; 2-(4-acetyl-1,2-dimethylpiperazin-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-me- thyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyrimidin-4-ylcarbonyl)- pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyrimidin-5-ylcarbonyl)- pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-methyl-1-[(1H-pyrazol-5-ylcarb- onyl)amino]ethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2R,4R)-1-acetyl-4-methoxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydrox- y-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{1-[(dimethylamino)(oxo)acetyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)-5-hy- droxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-{1-[4-({[4-fluoro-2-(methylsulfonyl)benzyl]amino}carbonyl)-5-hydroxy-1-- methyl-6-oxo-1,6-dihydropyrimidin-2-yl]-1-methylethyl}imidazo[2,1-b][1,3]t- hiazole-6-carboxamide; 2-[(2R,4R)-1-benzoyl-4-methoxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydro- xy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-[4-(isopropylsulfonyl)-1-methylpiperazin-2- -yl]-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[1,2-dimethyl-4-(methylsulfonyl)piperazin-2-yl]-N-(4-fluorobenzyl)-5-hy- droxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-2-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl- ]-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-[(methylsulfonyl)acetyl]pyrrol- idin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S)-1-acetyl-4,4-difluoropyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydrox- y-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2R,4R)-1-acetyl-4-ethoxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy- -1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S)-4,4-difluoro-1-methylpyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydrox- y-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridazin-3-ylcarb- onyl)pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[morpholin-4-yl(oxo)- acetyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{(2R,4R)-1-[(dimethylamino)(oxo)acetyl]-4-methoxypyrrolidin-2-yl}-N-(4-- fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide- ; 2-[(2S)-4,4-difluoro-1-(pyrazin-2-ylcarbonyl)pyrrolidin-2-yl]-N-(4-fluor- obenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{(2S,4S)-1-methyl-4-[(methylsulfo- nyl)amino]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{1-[(dimethylamino)sulfonyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)-5-hydro- xy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{(2R,4R)-4-ethoxy-1-[(methylamino)(oxo)acetyl]pyrrolidin-2-yl}-N-(4-flu- orobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S)-4,4-difluoro-1-(pyridazin-3-ylcarbonyl)pyrrolidin-2-yl]-N-(4-fluo- robenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-[(2S)-4,4-difluoro-1-(pyridin-2-ylcarbonyl)pyrrolidin-2-yl]-N-(4-fluoro- benzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{(2S)-1-[(dimethylamino)(oxo)acetyl]-4,4-difluoropyrrolidin-2-yl}-N-(4-- fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide- ; N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-[morpholin-4-yl(oxo)acetyl]py- rrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{(2S)-1-[(dimethylamino)(oxo)acetyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)- -5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{(2S)-1-[(dimethylamino)(oxo)acetyl]pyrrolidin-2-yl}-N-(4-fluoro-2-meth- oxybenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N1-[1-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-oxo-1,6-d- ihydropyrimidin-2-yl)-1-methylethyl]-N1,N2,N2-trimethylethanediamide; 2-[(2S)-1-acetylpyrrolidin-2-yl]-N-(4-fluoro-2-methoxybenzyl)-5-hydroxy-1- -methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N-(4-fluorobenzyl)-2-[(2S,4S)-4-fluoro-1-methylpyrrolidin-2-yl]-5-hydroxy- -1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; 2-{(2S,4S)-1-[(dimethylamino)(oxo)acetyl]-4-fluoropyrrolidin-2-yl}-N-(4-f- luorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide; N1-[1-(4-{[(3-chloro-4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-- oxo-1,6-dihydropyrimidin-2-yl)-1-methylethyl]-N2,N2-dimethylethanediamide; and pharmaceutically acceptable salts thereof; and (ii) a reverse transcriptase inhibitor selected from the group consisting of efavirenz, emtricitabine, lamivudine, tenofovir disoproxil fumarate and zidovudine. 2. The combination according to claim 1, wherein the compound is N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxa- diazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamid- e or a pharmaceutically acceptable salt thereof. 3. The combination according to claim 2, wherein the reverse transcriptase inhibitor is lamivudine. |
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