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 method of treating a disorder which is responsive to antagonism of the adenosine A 2B receptor in a subject in need thereof, the method comprising administering to the subject a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is:
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. The method of claim 1 , wherein the disorder is an inflammatory disease.
3. The method of claim 2 , wherein the inflammatory disease is rheumatoid arthritis, multiple sclerosis, lupus, psoriasis, or inflammatory bowel disease.
4. The method of claim 1 , wherein the disorder is nociception, asthma, chronic obstructive pulmonary disease, diabetes, or diabetic retinopathy.
5. The method of claim 1 , comprising orally administering to the subject the compound of formula (I) or the pharmaceutically acceptable salt thereof.
6. The method of claim 5 , wherein R 1 is an optionally substituted 5- or 6-membered heteroaryl ring.
7. The method of claim 1 , wherein R 1 is an optionally substituted 5-membered heteroaryl ring.
8. The method of claim 1 , wherein R 1 is thienyl optionally substituted by fluoro, chloro, bromo, cyano, methyl, trifluoromethyl, ethyl, hydroxyl, hydroxymethyl, or hydroxyethyl.
9. The method of 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.
10. The method of claim 1 , wherein R 2 is an optionally substituted 5- or 6-membered monocyclic heteroaryl group linked via a C 1 -C 6 alkylene chain.
11. The method of claim 1 , 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.
12. The method of 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.
13. The method of claim 1 , wherein R 3 is an optionally substituted 5- or 6-membered monocyclic heteroaryl group linked via a C 1 -C 6 alkylene chain.
14. The method of claim 1 , wherein R 4 is amino, methylamino, ethylamino, or ethyl.
15. A method of treating a disorder which is responsive to antagonism of the adenosine A 2B receptor in a subject in need thereof, the method comprising administering to the subject a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein the compound of formula (II) is:
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.
16. The method of claim 15 , wherein the disorder is an inflammatory disease.
17. The method of claim 16 , wherein the inflammatory disease is rheumatoid arthritis, multiple sclerosis, lupus, psoriasis, or inflammatory bowel disease.
18. The method of claim 15 , wherein the disorder is nociception, asthma, chronic obstructive pulmonary disease, diabetes, or diabetic retinopathy.
19. The method of claim 15 , comprising orally administering to the subject the compound of formula (I) or the pharmaceutically acceptable salt thereof.
20. The method of claim 15 , wherein R 1 is thien-2-yl, R 2 is hydrogen, and R 3 is pyrid-3-yl-methyl, and R 4 is hydrogen or methyl.