Thienopyrimidine compounds
Compounds of formula (I) are A 2B receptor antagonists, wherein R 1 is optionally substituted aryl or an optionally substituted 5- or 6-membered heteroaryl ring; R 2 and R 3 are independently selected from hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-(C 1 -C 6 )-alkyl, aryl-(C 1 -C 6 )-alkyl optionally substituted in the ring part thereof, a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C 1 -C 6 alkylene chain and optionally substituted in the ring part thereof, benzimidazol-2-yl-methyl, pyrid-3-yl-carbonyl, or (1-methyl-piperidin-4-yl)-carbonyl-methyl; or R 2 and R 3 taken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring; R 4 is C 1 -C 3 alkyl, C 2 -C 3 alkenyl, —N(—R 5 )—R 6 , or optionally substituted heteroarylmethylamino; and R 5 and R 6 are independently selected from hydrogen or C 1 -C 3 alkyl; or R 5 and R 6 taken together with the nitrogen atom to which they are attached form an optionally substituted 4- to 6-membered saturated ring.
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein
R 1 is optionally substituted aryl or an optionally substituted 5- or 6-membered heteroaryl ring;
R 2 and R 3 are independently selected from hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-(C 1 -C 6 )-alkyl, aryl-(C 1 -C 6 )-alkyl optionally substituted in the ring part thereof, a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C 1 -C 6 alkylene chain and optionally substituted in the ring part thereof, benzimidazol-2-yl-methyl, pyrid-3-yl-carbonyl, or (1-methyl-piperidin-4-yl)-carbonyl-methyl;
or R 2 and R 3 taken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring;
R 4 is C 1 -C 3 alkyl, C 2 -C 3 alkenyl, —N(—R 5 )—R 6 , or optionally substituted heteroarylmethylamino; and
R 5 and R 6 are independently selected from hydrogen or C 1 -C 3 alkyl;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached form an optionally substituted 4- to 6-membered saturated ring.
2. A compound as claimed in claim 1 wherein R 1 is an optionally substituted 5- or 6-membered heteroaryl ring.
3. A compound as claimed in claim 1 wherein R 1 is an optionally substituted 5-membered heteroaryl ring.
4. A compound as claimed in claim 1 wherein R 1 is optionally substituted thienyl.
5. A compound as claimed in claim 4 wherein R 1 is thienyl optionally substituted by fluoro, chloro, bromo, cyano, methyl, trifluoromethyl, ethyl, hydroxyl, hydroxymethyl, or hydroxyethyl.
6. A compound as claimed in claim 1 wherein R 1 is thien-2-yl.
7. A compound as claimed in claim 1 wherein R 2 is hydrogen, or a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C 1 -C 6 alkylene chain and optionally substituted in the ring part thereof.
8. A compound as claimed in claim 7 wherein R 2 is hydrogen.
9. A compound as claimed in claim 7 wherein R 2 is an optionally substituted 5- or 6-membered monocyclic heteroaryl group linked via a C 1 -C 6 alkylene chain.
10. A compound as claimed in claim 7 wherein R 2 is a 5- or 6-membered monocyclic heteroaryl group linked via a C 1 -C 6 alkylene chain and optionally substituted in the ring part thereof by fluoro, chloro, bromo, cyano, methyl, trifluoromethyl, ethyl, hydroxyl, hydroxymethyl, or hydroxyethyl.
11. A compound as claimed in claim 1 wherein R 3 is hydrogen, or a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C 1 -C 6 alkylene chain and optionally substituted in the ring part thereof.
12. A compound as claimed in claim 11 wherein R 3 is an optionally substituted 5- or 6-membered monocyclic heteroaryl group linked via a C 1 -C 6 alkylene chain.
13. A compound as claimed in claim 11 wherein R 3 is a 5- or 6-membered monocyclic heteroaryl group linked via a C 1 -C 6 alkylene chain and optionally substituted in the ring part thereof by fluoro, chloro, bromo, cyano, methyl, trifluoromethyl, ethyl, hydroxyl, hydroxymethyl, or hydroxyethyl.
14. A compound as claimed in claim 1 wherein R 4 is amino.
15. A compound as claimed in claim 1 wherein R 4 is mono C 1 -C 3 alkylamino.
16. A compound as claimed in claim 15 wherein R 4 is methylamino.
17. A compound as claimed in claim 15 wherein R 4 is ethylamino.
18. A compound as claimed in claim 1 wherein R 4 is C 1 -C 3 alkyl.
19. A compound as claimed in claim 18 wherein R 4 is ethyl.
20. A compound of formula (II) or a pharmaceutically acceptable salt thereof:
wherein
R 1 is optionally substituted aryl or an optionally substituted 5- or 6-membered heteroaryl ring;
R 2 and R 3 are independently selected from hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-(C 1 -C 6 )-alkyl, aryl-(C 1 -C 6 )-alkyl optionally substituted in the ring part thereof, a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C 1 -C 6 alkylene chain and optionally substituted in the ring part thereof, benzimidazol-2-yl-methyl, pyrid-3-yl-carbonyl, or (1-methyl-piperidin-4-yl)-carbonyl-methyl;
or R 2 and R 3 taken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring; and
R 4 is hydrogen or C 1 -C 3 alkyl.
21. A compound as claimed in claim 20 wherein R 1 is thien-2-yl.
22. A compound as claimed in claim 20 wherein R 2 is hydrogen and R 3 is pyrid-3-ylmethyl.
23. A compound as claimed in claim 20 wherein R 4 is hydrogen or methyl.
24. A pharmaceutical composition comprising a compound as claimed in claim 1 and a pharmaceutically acceptable carrier.
25. A compound as claimed in claim 1 wherein R 1 is thien-2-yl, R 2 is hydrogen, and R 3 is pyrid-3-ylmethyl.