Substituted thieno[2,3-d]pyrimidin-2,4-dione compounds and uses thereof
The present invention provides a compound represented by the formula: wherein R 1 is a C 1-4 alkyl; R 2 is (1) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a hydroxy group, (3′) a C 1-4 alkyl and (4′) a C 1-4 alkoxy, (2) a phenyl which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a C 1-4 alkoxy-C 1-4 alkyl, (3′) a mono-C 1-4 alkyl-carbamoyl-C 1-4 alkyl, (4′) a C 1-4 alkoxy and (5′) a mono-C 1-4 alkylcarbamoyl-C 1-4 alkoxy, or the like; R 3 is a C 1-4 alkyl; R 4 is a C 1-4 alkoxy, or the like; n is an integer of 1 to 4; or a salt thereof, as a thienopyrimidine compound having gonadotropin-releasing hormone antagonistic activity.
1. A compound of the formula (I):
wherein
R 1 is a C 1-4 alkyl;
R 2 is a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a hydroxy group, (3′) a C 1-4 alkyl and (4′) a C 1-4 alkoxy;
R 3 is a C 1-4 alkyl;
R 4 is
(1) a hydrogen atom,
(2) a C 1-4 alkoxy,
(3) a C 6-10 aryl,
(4) a N—C 1-4 alkyl-N—C 1-4 alkylsulfonylamino,
(5) a hydroxyl group, or
(6) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) oxo, (2′) a C 1-4 alkyl, (3′) a hydroxy-C 1-4 alkyl, (4′) a C 1-4 alkoxy-carbonyl, (5′) a mono-C 1-4 alkyl-carbamoyl and (6′) a C 1-4 alkylsulfonyl;
n is an integer of 1 to 4;
or a salt thereof.
2. The compound as claimed in claim 1 , wherein
R 4 is
(1) a C 1-4 alkoxy,
(2) a C 6-10 aryl,
(3) a N—C 1-4 alkyl-N—C 1-4 alkylsulfonylamino, or
(4) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) oxo, (2′) a hydroxy-C 1-4 alkyl, (3′) a C 1-4 alkoxycarbonyl, (4′) a mono-C 1-4 alkyl-carbamoyl and (5′) a C 1-4 alkylsulfonyl.
3. The compound as claimed in claim 1 , wherein R 1 is methyl.
4. The compound as claimed in claim 1 , wherein R 3 is methyl.
5. The compound as claimed in claim 1 , wherein R 4 is a C 1-4 alkoxy.
6. The compound as claimed in claim 1 , wherein n is 2.
7. The compound as claimed in claim 1 , wherein R 3 is methyl, R 4 is a hydrogen atom and n is 1.
8. N-(4-(1-(2,6-difluorobenzyl)-5(((2-methoxyethyl)(methyl)amino)methyl)-2,4-dioxo-3-(2-pyridinyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxypyridin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a salt thereof.
9. A pharmaceutical composition which comprises the compound compound of claim 1 or a salt thereof with a pharmacologically acceptable carrier, excipient or diluent.
10. A method for manufacturing a pharmaceutical composition for antagonizing gonadotropin-releasing hormone which comprises mixing the compound of claim 1 or a salt thereof with a pharmacologically acceptable carrier, excipient or diluent.
11. N-(4-(1-(2,6-difluorobenzyl)-5(((2-methoxyethyl)(methyl)amino)methyl)-2,4-dioxo-3-(2-pyridinyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea or a salt thereof.
12. N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxypyridin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea or a salt thereof.