Pyrazoloquinoline derivatives

A method for improving cognitive impairment in Alzheimer's disease, comprising administering to a patient in need thereof a compound represented by the formula (I) or a pharmacologically acceptable salt thereof:

• wherein
• R1 is a hydrogen atom;
• R2 is an aromatic ring group selected from the group consisting of a phenyl group, a pyridinyl group, and a pyrimidinyl group, where the two atoms on the aromatic ring which are adjacent to the carbon atom attached to the pyrazolo[4,3-c]quinoline ring each independently has a substituent selected from Group A1, and the other atoms on the aromatic ring independently optionally have a substituent selected from Group B 1;
• R3 is a hydrogen atom, or a fluorine atom;
• R4 is a hydrogen atom;
• R5 is an oxepanyl group, a dioxepanyl group, a tetrahydropyranyl group, or a tetrahydrofuranyl group optionally substituted with a methoxy group;
• R6 is a hydrogen atom;
• Group A1 consists of a halogen atom, a C1-6 alkyl group optionally substituted with 1 to 3 halogen atoms, and a C1-6 alkoxy group;
• and
• Group B1 consists of a halogen atom, a cyano group, a C1-6 alkyl group optionally substituted with 1 to 3 halogen atoms, a C1-6 alkoxy-C1-6 alkyl group, a C1-6 alkoxy group optionally substituted with 1 to 3 halogen atoms, and a tetrahydropyranyl group,
• with the proviso that when R2 is a 3-pyridinyl group, the substituent at the 4-position is a halogen atom, or a C1-6 alkyl group optionally substituted with 1 to 3 halogen atoms.

A method for improving cognitive impairment in Alzheimer's disease, comprising administering to a patient in need thereof a compound selected from the group consisting of:

• 1) 7-(6-methoxy-2,4-dimethylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 2) 7-(2-methoxy-4,6-dimethylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 3) (S)-7-(6-isopropyloxy-2,4-dimethylpyridin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 4) 8-fluoro-7-(2-methoxy-4,6-dimethylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 5) 1-(1,4-dioxepan-6-yl)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 6) 1-(1,4-dioxepan-6-yl)-7-(2-methoxy-4,6-dimethylpyridin-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 7) (S)-8-fluoro-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 8) 7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 9) (−)-7-(2-methoxy-4,6-dimethylpyridin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 10) (−)-7-(6-methoxy-2,4-dimethylpyridin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 11) (S)-8-fluoro-7-(2-methoxy-4,6-dimethylpyridin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 12) (S)-7-(6-ethoxy-2,4-dimethylpyridin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• 13) (S)-8-fluoro-7-(6-methoxy-2,4-dimethylpyridin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one, and
• 14) (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one,
• or a pharmacologically acceptable salt of any of the aforementioned.

A method for increasing intracerebral cGMP concentration, comprising administering to a patient in need thereof a compound represented by the formula (I) or a pharmacologically acceptable salt thereof:

• wherein
• R1 is a hydrogen atom;
• R2 is an aromatic ring group selected from the group consisting of a phenyl group, a pyridinyl group, and a pyrimidinyl group, where the two atoms on the aromatic ring which are adjacent to the carbon atom attached to the pyrazolo[4,3-c]quinoline ring each independently has a substituent selected from Group A1, and the other atoms on the aromatic ring independently optionally have a substituent selected from Group B 1;
• R3 is a hydrogen atom, or a fluorine atom;
• R4 is a hydrogen atom;
• R5 is an oxepanyl group, a dioxepanyl group, a tetrahydropyranyl group, or a tetrahydrofuranyl group optionally substituted with a methoxy group;
• R6 is a hydrogen atom;
• Group A1 consists of a halogen atom, a C1-6 alkyl group optionally substituted with 1 to 3 halogen atoms, and a C1-6 alkoxy group;
• and
• Group B 1 consists of a halogen atom, a cyano group, a C1-6 alkyl group optionally substituted with 1 to 3 halogen atoms, a C1-6 alkoxy-C1-6 alkyl group, a C1-6 alkoxy group optionally substituted with 1 to 3 halogen atoms, and a tetrahydropyranyl group,
• with the proviso that when R2 is a 3-pyridinyl group, the substituent at the 4-position is a halogen atom, or a C1-6 alkyl group optionally substituted with 1 to 3 halogen atoms.