Pyridinylpyrazoloquinoline compounds

Patent metadata

Field	Value
Publication number	US-9550776-B2
Application number	US-201414778202-A
Country	US
Kind code	B2
Filing date	Apr 3, 2014
Priority date	Apr 5, 2013
Publication date	Jan 24, 2017
Grant date	Jan 24, 2017

Abstract

A compound represented by formula (I), or a pharmaceutically acceptable salt thereof:

wherein R 1 represents a group represented by the formula:

a group represented by the formula:

or a group represented by the formula:

and R 2 represents a 3-methyltetrahydro-2H-pyran-4-yl group or 4-methoxycyclohexyl group.

First claim

The invention claimed is:

1. A compound represented by formula (I), or a pharmaceutically acceptable salt thereof:

wherein R 1 is a group represented by the formula:

a group represented by the formula:

or a group represented by the formula:

and R 2 is a 3-methyltetrahydro-2H-pyran-4-yl group or 4-methoxycyclohexyl group.

2. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is represented by formula (II):

wherein R 3 is a group represented by the formula:

or a group represented by the formula:

3. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is represented by formula (III):

wherein R 2 is a 3-methyltetrahydro-2H-pyran-4-yl group or 4-methoxycyclohexyl group.

4. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is (-)-7-(6-Methoxy-2,4-dimethylpyridin-3-yl)-1-((3R*,4R*)-3-methyltetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinoline-4(5H)-one ((-)-cis):

5. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is (-)-7-(6-Methoxy-2,4-dimethylpyridin-3-yl)-1-((3R*,4S*)-3-methyltetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinoline-4(5H)-one ((-)-trans):

6. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is (-)-7-(2-Methoxy-4,6-dimethylpyridin-3-yl)-1-((3R*,4S*)-3-methyltetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinoline-4(5H)-one ((-)-trans):

7. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is (-)-7-(2-Methoxy-3,5-dimethylpyridin-4-yl)-1-((3R*,4R*)-3-methyltetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinoline-4(5H)-one ((-)-cis):

8. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is 7-(2-Methoxy-3,5-dimethylpyridin-4-yl)-1-(trans-4-methoxycyclohexyl)-1H-pyrazolo[4,3-c]quinoline-4(5H)-one:

9. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.

10. A method for improving cognitive impairment in Alzheimer's disease in a patient in need thereof, comprising administering the compound or pharmaceutically acceptable salt thereof according to claim 1 to the patient.

11. A method for increasing intracerebral cGMP concentration in a patient in need thereof, comprising administering the compound or pharmaceutically acceptable salt thereof according to claim 1 to the patient.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Norimine Yoshihiko
• Sato Nobuaki
• Ishihara Yuki
• Takeda Kunitoshi

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title