Compounds having PDE9A inhibitory activity, and pharmaceutical uses thereof
The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
1. A compound represented by the following Chemical formula 1 or a pharmaceutically acceptable salt thereof,
In Chemical Formula 1,
A is phenyl unsubstituted or substituted with one or more halogens, C 1-5 straight or branched alkyl unsubstituted or substituted with one or more halogens, 3 to 6 membered cycloalkyl unsubstituted or substituted with one or more halogens, or 3 to 6 membered heterocycloalkyl unsubstituted or substituted with one or more halogens, and
R 1 and R 2 are each independently —H, halogen, —NO 2 , —CF 3 , phenyl unsubstituted or substituted with one or more halogens, C 1-5 straight or branched alkyl unsubstituted or substituted with one or more halogens, or C 1-5 straight or branched alkoxy unsubstituted or substituted with one or more halogens,
with a proviso that the compound is not 6-((benzo[d]oxazol-2-ylmethyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one.
2. The compound or a pharmaceutically acceptable salt thereof according claim 1 , wherein
A is phenyl, C 1-5 straight or branched alkyl unsubstituted or substituted with one or more halogens, or 3 to 6 membered heterocycloalkyl unsubstituted or substituted with one or more halogens, and
R 1 and R 2 are each independently —H, halogen, —NO 2 , —CF 3 , phenyl, C 1-5 straight or branched alkyl unsubstituted or substituted with one or more halogens, or C 1-5 straight or branched alkoxy unsubstituted or substituted with one or more halogens.
3. The compound or a pharmaceutically acceptable salt thereof according claim 2 , wherein
A is phenyl,
and
R 1 and R 2 are each independently —H, halogen, —NO 2 , —CF 3 , —CH 3 , —C(CH 3 ) 3 , or phenyl.
4. The compound or a pharmaceutically acceptable salt thereof according claim 1 , wherein the compound is
6-((benzo[d]oxazol-2-ylmethyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-fluorobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-chlorobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-bromobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((benzo[d]oxazol-2-ylmethyl)thio)-1-(4,4-difluorocyclohexyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((benzo[d]oxazol-2-ylmethyl)thio)-1-(tetrahydro-2H-thiopyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((benzo[d]oxazol-2-ylmethyl)thio)-1-cyclopropyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((benzo[d]oxazol-2-ylmethyl)thio)-1-isopropyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((benzo[d]oxazol-2-ylmethyl)thio)-1-cyclohexyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-(4,4-difluorocyclohexyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-thiopyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-cyclohexyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-cyclopropyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-isopropyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((1-(benzo[d]oxazol-2-yl)ethyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((1-benzo[d]oxazol-2-yl)ethyl)thio)-1-(4,4-difluorocyclohexyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((1-benzo[d]oxazol-2-yl)ethyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-((1-(6-methylbenzo[d]oxazol-2-yl)ethyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((1-(6-methylbenzo[d]oxazol-2-yl)ethyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-((1-(6-methylbenzo[d]oxazol-2-yl)ethyl)thio)-1-(tetrahydro-2H-thiopyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-phenyl-6-(((5-phenylbenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((4-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazole[3,4-d]pyrimidin-4-one,
6-(((5-(tert-butyl)benzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((4-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-nitro-6-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5,7-dichlorobenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5,7-dimethylbenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-methoxybenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-methoxybenzo[d]oxazol-2-yl)methyl)thio)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-phenyl-6-(((5-(trifluoromethyl)benzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((6-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((5-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((4-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-chloro-6-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-(4,4-difluorocyclohexyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((4-methylbenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-(tert-butyl)benzo[d]oxazol-2-yl)methyl)thio)-1-(4,4-difluorocyclohexyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5,7-dichlorobenzo[d]oxazol-2-yl)methyl)thio)-1-(4,4-difluorocyclohexyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((5,7-dimethylbenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((5-methoxybenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((6-methoxybenzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
1-(4,4-difluorocyclohexyl)-6-(((5-(trifluoromethyl)benzo[d]oxazol-2-yl)methyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((6-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((4-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-chloro-6-nitrobenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((4-methylbenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5-(tert-butyl)benzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5,7-dichlorobenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one,
6-(((5,7-dimethylbenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, or
6-(((6-methoxybenzo[d]oxazol-2-yl)methyl)thio)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one.
5. A composition comprising the compound or a pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier.