2-morpholino-4-pyrimidone compound
View Patent ↗A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein X represents CH or N; represents a C 1 -C 12 alkyl; R 2 represents a hydrogen atom, or the like; R′ represents a C 1 -C 6 alkyl or the like; q represents 0 or an integer of 1 to 7; Y represents a C 1 -C 6 alkyl or the like; p represents 0 or an integer of 1 to 5; R represents a 2,3-dihydroindolyl or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).
1. A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof;
wherein each symbol is as defined below;
X represents CH or N;
R 1 represents a C 1 -C 12 alkyl;
R 2 represents a hydrogen atom;
R represents
a formula (1);
in the formula (1), R 3 represents a hydrogen atom, or
a C 1 -C 6 alkyl which may be substituted by hydroxyl or a C 1 -C 6 alkoxy;
R 4 represents
a formula (3)
wherein m represents 0 or an integer of 1 to 4,
Z 1 represents a carbonyl group,
R20 and R21 are the same or different and each represents a hydrogen atom or a C 1 -C 6 alkyl;
R 7 represents a C 1 -C 6 alkyl which may be substituted by hydroxyl or halogen atom,
a C 3 -C 7 cycloalkyl which may be substituted by C 1 -C 6 alkyl, hydroxyl or C 1 -C 6 alkoxy,
a C 6 -C 10 aryl which may be substituted by N,N-di-C 1 -C 6 alkylamino,
a heterocyclic group which may be substituted by phenyl or C 1 -C 6 alkyl, or
a C 1 -C 6 alkoxy which may be substituted by phenyl.
2. The compound, an optically active isomer thereof, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is methyl group.
3. A compound according to claim 1 selected from the group consisting of:
N-(4-(4-(1-Methyl-6-oxo-4-(pyridin-4-yl)-1,6-dihydropyrimidin-2-yl)morpholin-2-yl)-phenyl)-acetamide,
N-(4-(4-(1,6-Dihydro-1-methyl-6-oxo-4,4′-bipyrimidin-2-yl)morpholin- 2-yl)phenyl)-acetamide,
2-(2-(4-Cyclopropylcarbonylamino)phenyl)morpholin-4-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one,
2-(2-(4-Cyclopropylcarbonylamino)phenyl)morpholin-4-yl)-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one,
N- {4-[(2S)-4-(1-Methyl-6-oxo-4-pyridin-4-yl-1,6-dihydropyrimidin-2-yl)morpholin-2-yl]phenyl}-2-pyrrolidin-1-ylacetamide,
N- {4-[(2S)-4-(1-Methyl-6-oxo-1,6-dihydro-4,4′-bipyrimidin-2-yl)morpholin-2-yl]Phenyl}-2-pyrrolidin-1-ylacetamide,
N2,N2-Dimethyl-N1- {4-[(2S)-4-(1 -methyl-6-oxo- 1,6-dihydro-4,4′-bipyrimidin-2-yl)-morpholin-2-yl]phenyl}glycinamide,
Methyl {4-[(2S)-4-(1-methyl-6-oxo-4-pyridin-4-yl-1,6-dihydropyrimidin-2-yl)-morpholin-2-yl]phenyl}carbamate,
Ethyl {4-[(2S)-4-(1-methyl-6-oxo-1,6-dihydro-4,4′-bipyrimidin-2-yl)morpholin-2-yl]-phenyl}carbamate,
N-{4-Methoxy-3-[(2S)-4-(1-methyl-6-oxo-4-pyridin-4-yl-1,6-dihydropyrimidin-2-yl)-morpholin-2-yl]phenyl}acetamide,
N-{4-Methoxy-3-[(2S)-4-(1-methyl-6-oxo-1,6-dihydro-4,4′-bipyrimidin-2-yl)morpholin-2-yl]phenyl}acetamide, and
N- { 3-[(2S)-4-(1-Methyl-6-oxo-4-pyridin-4-yl- 1,6-dihydropyrimidin-2-yl)morpholin-2-yl]phenyl}acetamide,
an optically active isomer thereof, or a pharmaceutically acceptable salt thereof.
4. A composition comprising as an active ingredient the compound represented by the formula (I) and an optically active isomer thereof, or a pharmaceutically acceptable salt thereof according to claim 1 .