3-substituted-4-pyrimidone derivatives
View Patent ↗A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof useful as a tau protein kinase 1 inhibitor: wherein X represents CH or nitrogen atom; R 1 represents a C?1#191-C?12#191 alkyl group which may be substituted; R 2 represents a C?1#191-C?8#191 alkyl group which may be substituted, a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total.
1. A pyrimidone compound represented by formula (I) or a salt thereof:
wherein X represents CH or nitrogen atom;
R 1 represents a C 1 -C 12 alkyl group which may be substituted;
R 2 represents a C 1 -C 8 alkyl group which may be substituted, a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total.
2. The pyrimidone compound or the salt thereof according to claim 1 , wherein R 1 is methyl group.
3. The pyrimidone compound or the salt thereof according to claim 1 , wherein the heterocyclic ring at R 2 is a group selected from a furan ring, a benzofuran ring, a thiophene ring, a benzothiophene ring, a benzisoxazole ring, and a 1H-indazole ring.
4. A pyrimidone compound which is selected from:
2-(5-phenyl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one; 2-[5-(4-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-bromophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-fluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-fluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2,4-difluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-chlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-chlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2,4-dichlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2,6-dimethoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-trifluoromethylphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(benzisoxazole-3-yl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-(5-benzyl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-(5-biphenyl-2-yl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-(5-thiophen-3-yl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-(5-thiophen-2-yl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-fluorophenoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-pyrrolidinylcarbonylphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one;
2-(5-phenyl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-bromophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-fluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-fluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2,4-difluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-chlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-chlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2,4-dichlorophenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2,6-dimethoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(2-trifluoromethylphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(benzisoxazole-3-yl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-(5-benzyl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-(5-biphenyl-2-yl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-(5-thiophen-3-yl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-(5-thiophen-2-yl-3,6-dihydro-2H-pyridin-1-yl)-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-fluorophenoxymethyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
2-[5-(4-pyrrolidinylcarbonylphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one;
and salts thereof.
5. A medicament composition comprising as an active ingredient a substance selected from the pyrimidone compound represented by formula (I) or a salt thereof according to claim 1 and a pharmaceutical excipient.
6. A method for treating of Alzheimer Disease, comprising:
administering the medicament composition according to claim 5 to a patient in need thereof.
7. A method for treating of rheumatoid arthritis, comprising:
administering the medicament composition according to claim 5 to a patient in need thereof.