US 2011/0034449 A1 · N-SUBSTITUTED HYDROXYPYRIMIDINONE CARBOXAMIDE INHIBITORS OF HIV INTEGRASE

N-substituted hydroxypyrimidinone carboxamide inhibitors of hiv integrase

AssigneeIstituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.

InventorsBenedetta Crescenzi, Cristina Gardelli, Ester Muraglia, Emanuela Nizi, Federica Orvieto, Paola Pace, Giovanna Pescatore, Alessia Petrocchi, Marco Poma, Michael Rowley, Rita Scarpelli, Vincenzo Summa

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Abstract

N-substituted 5-hydroxypyrimidin-6-one-4-carboxamides of formula: are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R1, R2, R3 and R4 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.

Claims7

Dependent claims

1-27. (canceled)

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-dihydropyrimidine-4-carboxamide;
N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-2-(4-methylphenyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(2,3-dimethoxybenzyl)-2-{4-[(dimethylamino)methyl]phenyl}-5-hydroxy-1-methyl-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-ylmethyl)phenyl]-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[4-(pyrrolidin-1-ylmethyl)phenyl]-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-[4-(piperidin-1-ylmethyl)phenyl]-1,6-dihydropyrimidine-4-carboxamide;
N-(2,3-dimethoxybenzyl)-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-(morpholin-4-ylmethyl)phenyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-{4-[(diethylamino)methyl]phenyl}-N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-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-dihydropyrimidine-4-carboxamide;
2-benzyl-N-(2,3-dimethoxybenzyl)-1-[2-(dimethylamino)ethyl]-5-hydroxy-6-oxo-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-ylpiperidin-1-yl)methyl]phenyl}-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-[4-fluoro-2-(trifluoromethyl)benzyl]-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(3-chloro-4-methylbenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-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-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-2-(4-{[(2R)-2-(methoxymethyl)pyrrolidin-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-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-6-oxo-1-(pyridin-3-ylmethyl)-1,6-dihydropyrimidine-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-dihydropyrimidine-4-carboxamide;
N-(2,3-dimethoxybenzyl)-5-hydroxy-6-oxo-1-(pyridin-3-ylmethyl)-1,6-dihydropyrimidine-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)methyl]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)methyl]benzyl}-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-2-pyrrolidin-2-yl-1,6-dihydropyrimidine-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-dihydropyrimidine-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-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[1-(N,N-dimethylglycyl)piperidin-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-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-tetrahydroquinolin-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-methyl-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-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-2-[(2S,4R)-4-hydroxypyrrolidin-2-yl]-1-methyl-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-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[(2S,4R)-1-benzoyl-4-(benzyloxy)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-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-methyl-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-dihydropyrimidin-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-oxo-1,6-dihydropyrimidine-4-carboxamide
(+)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide
2-(1-ethyl-2,3-dihydro-1H-indol-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-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)piperidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(2-methyl-1,2,3,4-tetrahydroisoquinolin-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)pyrrolidin-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-fluorobenzyl)-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-hydroxy-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-methyl-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-methyl-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-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-[(4-methylmorpholin-3-yl)carbonyl]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-(1,4-dimethylpiperazin-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-3-ylcarbonyl)pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide;
2-[(2S,4R)-1-acetyl-4-(benzyloxy)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-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)carbonyl]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[(2S,4R)-1-acetyl-4-hydroxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[1-(anilinocarbonyl)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-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)pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide;
2-[(4R)-3-acetyl-1,3-thiazolidin-4-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-(methylsulfonyl)piperazin-2-yl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylthiomorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-[4-fluoro-2-(methylsulfonyl)benzyl]-5-hydroxy-1-methyl-6-oxo-2-[1-(pyrazin-2-ylcarbonyl)pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide;
2-(1-acetylpyrrolidin-2-yl)-N-[4-fluoro-2-(methylsulfonyl)benzyl]-5-hydroxy-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-methylethyl}-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-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[4-(benzyloxy)-1-(pyrazin-2-ylcarbonyl)pyrrolidin-2-yl]-N-(4-fluorobenzyl)-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-dihydropyrimidin-2-yl)-1-methylethyl]-N2,N2-dimethylethanediamide;
2-(1-acetylpyrrolidin-2-yl)-N-[2-(dimethylamino)benzyl]-5-hydroxy-1-methyl-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)pyrrolidin-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-dihydropyrimidin-2-yl)-1-methylethyl]imidazo[2,1-b][1,3]thiazole-6-carboxamide;
2-[(2S,4S)-1-acetyl-4-fluoropyrrolidin-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-[(1-methyl-1H-imidazol-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-oxadiazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
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-dimethylethanediamide;
2-(4-acetyl-1,2-dimethylpiperazin-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-(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-ylcarbonyl)amino]ethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[(2R,4R)-1-acetyl-4-methoxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-{1-[(dimethylamino)(oxo)acetyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)-5-hydroxy-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]thiazole-6-carboxamide;
2-[(2R,4R)-1-benzoyl-4-methoxypyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-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-hydroxy-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]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-[(2S)-1-acetyl-4,4-difluoropyrrolidin-2-yl]-N-(4-fluorobenzyl)-5-hydroxy-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-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(2,3-dimethoxybenzyl)-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridazin-3-ylcarbonyl)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-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{(2S,4S)-1-methyl-4-[(methylsulfonyl)amino]pyrrolidin-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-{1-[(dimethylamino)sulfonyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;
2-{(2R,4R)-4-ethoxy-1-[(methylamino)(oxo)acetyl]pyrrolidin-2-yl}-N-(4-fluorobenzyl)-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-fluorobenzyl)-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-fluorobenzyl)-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]pyrrolidin-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-methoxybenzyl)-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-dihydropyrimidin-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-fluorobenzyl)-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) an antiviral selected from the group consisting of HIV protease inhibitors, non-nucleoside HIV reverse transcriptase inhibitors and nucleoside HIV reverse transcriptase inhibitors.

165 more elements

Dependencies are inferred from the claim text.

Facts

Application

12/884,734Filed 17 Sep 2010

Priority

26 Oct 2001

Published

10 Feb 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

C07D 239/557
With other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring…:…
A61P 31/18
For RNA viruses: for HIV
A61P 37/00
Drugs for immunological or allergic disorders
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Family

Application60/339,568Us provisional application · filed 26 Oct 2001

Application60/362,191Us provisional application · filed 6 Mar 2002

Application10/493,280Division · filed 20 Apr 2004

Application11/641,508Division · filed 19 Dec 2006

Application12/214,595Continuation · filed 20 Jun 2008

Application12/884,734Continuation

Application12/214,595Division

US 2005/0025774 A1Published application

US 2007/0123524 A1Published application

US 2008/0275004 A1Published application

US 7,169,780 B2Related patent

US 7,435,734 B2Related patent

US 7,820,660 B2Related patent

US 2011/0034449 A1This patent

From the US filing history. Foreign family members aren’t listed.