2-oxonaphthyridine-3-carboxamides HIV integrase inhibitors

1. A compound selected from the group consisting of:

7-(4-Fluorobenzyl)-4-hydroxy-N-(2-methoxyethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

N-Cyclopropyl-7-(4-fluorobenzyl)-4-hydroxy-2-oxo-1-[2-(2-oxopyrrolidin-l-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-(4-Fluorobenzyl)-4-hydroxy-N-(2-morpholin-4-ylethyl)-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-Benzyl-4-hydroxy-N-(2-methoxyethyl)-1-(2-morpholin-4-yl-2-oxoethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

4-Hydroxy-N-[2-(methyloxy)ethyl]-2-oxo-7-(phenylmethyl)-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-2-oxo-N-[3-(2-oxo-1-pyrrolidinyl)propyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-[2-(4-morpholinyl)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(5-Fluoro-2-pyridinyl)methyl]-4-hydroxy-N-[3-(4-morpholinyl)propyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-Benzyl-4-hydroxy-N-(2-methoxyethyl)-1-[4-(methylsulfonyl)benzyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-(4-Fluorobenzyl)-4-hydroxy-N-(2-methoxyethyl)-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-Benzyl-4-hydroxy-N-(2-methoxyethyl)-1-[(1-methyl-1H-imidazol-2-yl)methyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-Benzyl-1-(cyclopropylmethyl)-4-hydroxy-N-(2-methoxyethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-Benzyl-4-hydroxy-N-(2-methoxyethyl)-2-oxo-1-(1,3-thiazol-2-ylmethyl)-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-(4-Fluorobenzyl)-4-hydroxy-N-(2-methoxyethyl)-1-[4-(methylsulfonyl)benzyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-[2-(4-morpholinyl)ethyl]-1-[2-(4-morpholinyl)-2-oxoethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-1-[2-(4-morpholinyl)-2-oxoethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-{2-[(2-hydroxyethyl)oxy]ethyl}-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

1-[2-(Dimethylamino)-2-oxoethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

1-[2-(Dimethylamino)-2-oxoethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[2-(4-morpholinyl)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-[2-(4-morpholinyl)-2-oxoethyl]-N-[3-(4-morpholinyl)propyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-[2-(4-morpholinyl)-2-oxoethyl]-2-oxo-N-[3-(2-oxo-1-pyrrolidinyl)propyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-1-[2-(4-morpholinyl)-2-oxoethyl]-2-oxo-1 ,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-methyl-N-[2-(4-morpholinyl)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-methyl-N-[3-(4-morpholinyl)propyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-methyl-2-oxo-N-[3-(2-oxo-1-pyrrolidinyl)propyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-1-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-oxo-1,2-dihydro-1,5 -naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-(2-{methyl[2-(methyloxy)ethyl]amino}-2-oxoethyl)-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

(±)-7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-[2-hydroxy-1-methylethyl]-1-(2-{methyl[2-(methyloxy)ethyl]amino}-2-oxoethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

(±)-7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-[(2-hydroxypropyl]-1-(2-{methyl[2-(methyloxy)ethyl]amino}-2-oxoethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

N-[2-(ethyloxy)ethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-1-(2-{methyl[2-(methyloxy)ethyl]amino}-2-oxoethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

1-[2-(Dimethylamino)-2-oxoethyl]-7-(4-fluorobenzyl)-4-hydroxy-N-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

2. A compound according claim 1 wherein the pharmaceutically acceptable salt is a sodium salt.

3. A method of treatment of an HIV infection in a human comprising administering to said human an antiviral effective amount of a compound according to claim 1 .

4. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 together with a pharmaceutically acceptable carrier.

5. A pharmaceutical composition according to claim 4 in the form of a tablet or capsule.

6. A pharmaceutical composition according to claim 4 in the form of a liquid or suspension.

7. A method of treatment of an HIV infection in a human comprising administering to said human a composition comprising a compound according to claim 1 and another therapeutic agent.

8. 7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-1 -methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

9. 7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide sodium salt.

10. A method of treatment of an HIV infection in a human comprising administering to said human an antiviral effective amount of 7-[(4-fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising an effective amount of 7-[(4-fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.

12. A pharmaceutical composition according to claim 11 in the form of a tablet or capsule.

13. A pharmaceutical composition according to claim 11 in the form of a liquid or suspension.

14. A method of treatment of an HIV infection in a human comprising administering to said human a composition comprising 7-[(4-fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide, or a pharmaceutically acceptable salt thereof, and another therapeutic agent.

15. A pharmaceutical composition according to claim 11 wherein said composition comprises at least one additional therapeutic agent.

16. A compound selected from the group consisting of:

sodium 1-ethyl-7-[(4-fluorophenyl)methyl]-3-({[(1S)-2-hydroxy-1-methylethyl]amino}carbonyl)-2-oxo-1,2-dihydro-1,5-naphthyridin-4-olate;

1-(2-Amino-2-oxoethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

1-(4-Fluorophenyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-(4-Fluorobenzyl)-4-hydroxy-N-[(2S)-2-hydroxypropyl]-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-(4-Fluorobenzyl)-4-hydroxy-N-[(2R)-2-hydroxypropyl]-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-[2-(methylamino)-2-oxoethyl]-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

7-[(4-Fluorophenyl)methyl]-4-hydroxy-1-[(1-methyl-1H-imidazol-2-yl)methyl]-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

N-[(2R)-2,3-Dihydroxypropyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

1-Ethyl-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[(1S)-2-hydroxy-l-methylethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

17. A compound according claim 16 wherein the pharmaceutically acceptable salt is a sodium salt.

18. A method of treatment of an HIV infection in a human comprising administering to said human an antiviral effective amount of a compound according to claim 16 .

19. A pharmaceutical composition comprising an effective amount of a compound according to claim 16 together with a pharmaceutically acceptable carrier.

20. A pharmaceutical composition according to claim 19 in the form of a tablet or capsule.

21. A pharmaceutical composition according to claim 19 in the form of a liquid or suspension.

22. A method of treatment of an HIV infection in a human comprising administering to said human a composition comprising a compound according to claim 16 and another therapeutic agent.