IP Library Granted Patent US 7,977,344
Granted Patent B2
US 7,977,344 · App. 12/031,764 · Granted Jul 12, 2011

Compounds

Assignee: GlaxoSmithKline LLC
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Quick Facts
Patent No.
US 7,977,344
App. No.
12/031,764
Granted
Jul 12, 2011
Kind
B2
Abstract

The present invention includes novel compounds useful in the treatment of various disorders in particular infectious diseases, cancer, and allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, and as vaccine adjuvants.

Claims (190)

1. A compound of formula (I):

wherein;

R 1 is C 1-8 alkylamino, C 1-8 alkoxy, C 3-7 cycloalkylC 1-6 alkylamino, C 3-7 cycloalkylC 1-6 alkoxy, C 1-3 alkoxyC 2-3 alkoxy, or Het b -C 1-3 alkoxy;

Het b is a 5- or 6-membered saturated aliphatic heterocyle containing one oxygen atom;

R 2 is —(CH 2 ) n -Het;

n is an integer having a value of 1 to 4;

Het is a 5- or 6-membered saturated aliphatic heterocycle containing one oxygen heteroatom, which heterocycle may be substituted by one or two C 1-4 alkyl groups;

or salts or solvates thereof.

2. A compound according to claim 1 wherein R 1 is C 1-6 alkylamino, C 1-8 alkoxy, C 3-7 cycloalkylC 1-6 alkylamino, C 3-7 cycloalkylC 1-6 alkoxy, C 1-3 alkoxyC 2-3 alkoxy, or Het b -C 1-3 alkoxy.

3. A compound according to claim 1 or claim 2 wherein R 1 is n-butoxy, n-butylamino, 2,2-dimethylpentyloxy, n-pentylamino, 3-methylbutoxy, 2-methylbutoxy, 1-methylbutoxy, 2-methylbutylamino, 3-methylbutylamino, 1-methylbutylamino, 2-(cyclopropyl)ethoxy, 2-(ethoxy)ethoxy, (1-methyl-2-methoxy)ethoxy, cyclohexylmethylamino, cyclopentylmethylamino, 2-(cyclopropyl)ethylamino, 2-(methyl)propoxy, cyclohexylmethoxy, methoxyethoxy, (2-tetrahydrofuranyl)methoxy, (2-tetrahydro-2H-pyranyl)methoxy, or 2-(iso-propoxy)ethoxy.

4. A compound according to claim 1 wherein n is 1.

5. A compound according to claim 1 wherein n is 2.

6. A compound according to claim 1 wherein n is 3.

7. A compound according to claim 1 wherein n is 4.

8. A compound according to claim 1 wherein n is 1 and Het is tetrahydrofuran-3-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, tetrahydrofuran-2-yl, 2,2-dimethyltetrahydro-2H-pyran-4-yl, or tetrahydro-2H-pyran-2-yl.

9. A compound according to claim 1 wherein n is 2 and Het is tetrahydro-2H-pyran-4-yl, tetrahydrofuran-2-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-2-yl, or tetrahydrofuran-3-yl.

10. A compound according to claim 1 wherein n is 3 and Het is tetrahydro-2H-pyran-3-yl.

11. A compound according to claim 1 wherein n is 4 and Het is tetrahydro-2H-pyran-3-yl.

12. A compound according to claim 1 wherein R 1 is n-butylamino, n-butoxy, or 2-(cyclopropyl)ethoxy.

13. A compound according to claim 1 wherein n is 1 and R 2 is tetrahydro-2H-pyran-4-yl or tetrahydrofuran-3-yl.

14. A compound according to claim 1 wherein R 1 is n-butylamino, n-butoxy, (R)-1-methyl butyloxy, (S)-1-methylbutyloxy, or 2-(cyclopropyl)ethoxy.

15. A compound according to claim 1 wherein Het is tetrahydrofuran-3-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, tetrahydrofuran-2-yl, 2,2-dimethyltetrahydro-2H-pyran-4-yl, or tetrahydro-2H-pyran-2-yl.

16. A compound according to claim 1 wherein Het is tetrahydro-2H-pyran-4-yl, tetrahydrofuran-2-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-2-yl, or tetrahydrofuran-3-yl.

17. A compound according to claim 1 wherein Het is tetrahydro-2H-pyran-3-yl.

18. A compound according to claim 1 wherein Het is tetrahydro-2H-pyran-3-yl.

19. A compound according to claim 1 wherein Het is tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-2-yl, 2,2-dimethyltetrahydro-2H-pyran-4-yl, tetrahydrofuran-3-yl, or tetrahydro-2H-pyran-2-yl.

20. A compound according to claim 1 wherein n is 2 and Het is tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-2-yl, 2,2-dimethyltetrahydro-2H-pyran-4-yl, tetrahydrofuran-3-yl, or tetrahydrofuran-2-yl.

21. A compound according to claim 1 wherein n is 3 and Het is tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-2-yl, 2,2-dimethyltetrahydro-2H-pyran-4-yl, tetrahydrofuran-3-yl, or tetrahydrofuran-2-yl.

22. A compound according to claim 1 wherein n is 4 and Het is tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-2-yl, 2,2-dimethyltetrahydro-2H-pyran-4-yl, tetrahydrofuran-3-yl, or tetrahydrofuran-2-yl.

23. A compound selected from the list consisting of:

6-amino-2-butoxy-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butoxy-9-(tetrahydro-2H-pyran-2-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butoxy-9-(tetrahydrofuran-2-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-(tetrahydro-2H-pyran-2-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-(tetrahydrofuran-2-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-(tetrahydrofuran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-(tetrahydro-2H-pyran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butoxy-9-(tetrahydrofuran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butoxy-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butoxy-9-(tetrahydro-2H-pyran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butoxy-9-[2-(tetrahydrofuran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-[2-(tetrahydrofuran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butoxy-9-[2-(tetrahydro-2H-pyran-3-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-[2-(tetrahydro-2H-pyran-3-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2,2-dimethylpentyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-(pentylamino)-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(3-methylbutyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-methylbutyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(1-methylbutyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-methylbutyl)amino]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(3-methylbutyl)amino]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(1-methylbutyl)amino]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butyloxy-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butyloxy-9-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butyloxy-9-[2-(tetrahydro-3-furanyl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[2-(tetrahydro-3-furanyl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one, isomer 1;

6-amino-2-{[2-(ethyloxy)ethyl]oxy}-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[1-methyl-2-(methoxy)ethyl]oxy}-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[2-(ethyloxy)ethyl]oxy}-9-(tetrahydro-2H-pyran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[1-methyl-2-(methoxy)ethyl]oxy}-9-(tetrahydro-2H-pyran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(cyclohexylmethyl)amino]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(cyclopentylmethyl)amino]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)amino]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-methylpropyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(cyclohexyl methyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[2-(methoxy)ethyl]oxy}-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[2-(methoxy)ethyl]oxy}-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(tetrahydro-2-furanylmethyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[3-(tetrahydro-2H-pyran-3-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-9-(tetrahydro-2H-pyran-4-ylmethyl)-2-[(tetrahydro-2H-pyran-2-yl methoxy]-7,9-dihydro-8H-purin-8-one;

6-amino-2-({2-[(1-methylethyl)oxy]ethyl}oxy)-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[4-(tetrahydro-2H-pyran-3-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)amino]-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)amino]-9-(tetrahydro-2H-pyran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

and salts or solvates thereof.

24. A compound selected from the list consisting of:

6-amino-2-(butyloxy)-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-(tetrahydro-2H-pyran-4-ylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-(tetrahydro-3-furanylmethyl)-7,9-dihydro-8H-purin-8-one;

and salts or solvates thereof.

25. A compound selected from the list consisting of:

6-amino-2-butoxy-9-[2-(tetrahydrofuran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butylamino-9-[2-(tetrahydro-2H-pyran-3-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butyloxy-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-butyloxy-9-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[3-(tetrahydro-2-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[4-(tetrahydro-2-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-{2-[(3S)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-{2-[(3R)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[3-(tetrahydro-3-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[4-(tetrahydro-3-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[3-(tetrahydro-2H-pyran-2-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[4-(tetrahydro-2H-pyran-2-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[3-(tetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butylamino)-9-[4-(2,2-dimethyltetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[3-(tetrahydro-2-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[4-(tetrahydro-2-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-{2-[(3S)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-{2-[(3R)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[3-(tetrahydro-3-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[4-(tetrahydro-3-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[3-(tetrahydro-2H-pyran-2-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[4-(tetrahydro-2H-pyran-2-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[3-(tetrahydro-2H-pyran-3-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[4-(tetrahydro-2H-pyran-3-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[3-(tetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9-[4-(2,2-dimethyltetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[2-(tetrahydro-2-furanyl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[3-(tetrahydro-2-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[4-(tetrahydro-2-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[2-(tetrahydro-3-furanyl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-{2-[(3S)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-{2-[(3R)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[3-(tetrahydro-3-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[4-(tetrahydro-3-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[3-(tetrahydro-2H-pyran-2-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[4-(tetrahydro-2H-pyran-2-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[2-(tetrahydro-2H-pyran-3-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[4-(tetrahydro-2H-pyran-3-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[3-(tetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[4-(2,2-dimethyltetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2-furanyl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[3-(tetrahydro-2-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-{2-[(3S)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-{2-[(3R)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[3-(tetrahydro-3-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[4-(tetrahydro-3-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[3-(tetrahydro-2H-pyran-2-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[4-(tetrahydro-2H-pyran-2-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2H-pyran-3-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[4-(tetrahydro-2H-pyran-3-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[3-(tetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-9-[2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)ethyl]-2-{[(S)-1-methylbutyl]oxy}-7,9-dihydro-8H-purin-8-one;

6-amino-9-[3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)propyl]-2-{[(1S)-1-methylbutyl]oxy}-7,9-dihydro-8H-purin-8-one;

6-amino-9-[4-(2,2-dimethyltetrahydro-2H-pyran-4-yl)butyl]-2-{[(1S)-1-methylbutyl]oxy}-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2-furanyl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[3-(tetrahydro-2-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-{2-[(3S)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-{2-[(3R)-tetrahydro-3-furanyl]ethyl}-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[3-(tetrahydro-3-furanyl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[4-(tetrahydro-3-furanyl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[3-(tetrahydro-2H-pyran-2-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[4-(tetrahydro-2H-pyran-2-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2H-pyran-3-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[4-(tetrahydro-2H-pyran-3-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[3-(tetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1R)-1-methylbutyl]oxy}-9-[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-9-[2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)ethyl]-2-{[(1R)-1-methylbutyl]oxy}-7,9-dihydro-8H-purin-8-one;

6-amino-9-[3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)propyl]-2-{[(1R)-1-methylbutyl]oxy}-7,9-dihydro-8H-purin-8-one;

6-amino-9-[4-(2,2-dimethyltetrahydro-2H-pyran-4-yl)butyl]-2-{[(1R)-1-methylbutyl]oxy}-7,9-dihydro-8H-purin-8-one;

and salts and solvates thereof.

26. A method for the treatment of asthma, which method comprises administering an effective amount of a compound as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof.

27. A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and optionally one or more pharmaceutically acceptable diluents or carriers.

28. A compound selected from the list consisting of:

6-amino-2-(butyloxy)-9[4-(tetrahydro-2H-pyran-3-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9[3-(tetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-(butyloxy)-9[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[3-(tetrahydro-2H-pyran-4-yl)propyl]-7, 9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[3-(tetrahydro-2H-pyran-4-yl)propyl]-7,9-dihydro-8H-purin-8-one, and;

6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-7, 9-dihydro-8H-purin-8-one, and;

6-amino-2-[(2-cyclopropylethyl)oxy]-9-[4-(tetrahydro-2H-pyran-4-yl)butyl]-7,9-dihydro-8H-purin-8-one;

and salts or solvates thereof.

Assignments (4)
CHANGE OF ADDRESS Recorded Apr 16, 2025
From: GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED
Reel/Frame 070854/0469 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 19, 2013
From: GLAXOSMITHKLINE LLC
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED
Reel/Frame 029827/0721 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 1, 2008
From: LAZARIDES, LINOS; SMITH, STEPHEN ALLAN; STOCKER, RICHARD; THEOBALD, COLIN JACK
To: GLAXO GROUP LIMITED
Reel/Frame 020888/0043 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 1, 2008
From: GLAXO GROUP LIMITED
To: SMITHKLINE BEECHAM CORPORATION
Reel/Frame 020888/0164 →
Continuity (4)
Provisional Application 60890523 · Feb 19, 2007
Provisional Application 60972313 · Sep 14, 2007
Provisional Application 61021921 · Jan 18, 2008
Related Publication 20090131458A1 · May 21, 2009