Salt of pyrazoloquinoline derivative, and crystal thereof

Patent metadata

Field	Value
Publication number	US-9573947-B2
Application number	US-201414778695-A
Country	US
Kind code	B2
Filing date	Apr 3, 2014
Priority date	Apr 5, 2013
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

The present invention provides a salt of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one and an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, malonic acid, maleic acid, tartaric acid, methanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid; or a crystal thereof with a potential to be used as drug substance in pharmaceuticals.

First claim

The invention claimed is:

1. A salt of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one formed with an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, malonic acid, maleic acid, tartaric acid, methanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid.

2. (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo [4,3-c]quinolin-4(5H)-one monomaleate salt according to claim 1 .

3. (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo [4,3-c]quinolin-4(5H)-one monobenzenesulfonate salt according to claim 1 .

4. A crystal of the salt according to claim 1 .

5. A crystal of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo [4,3-c]quinolin-4(5H)-one monomaleate salt according to claim 4 , having a diffraction peak at a diffraction angle 2θ±0.2° of 10.1° in powder X-ray diffraction.

6. A crystal of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one monobenzenesulfonate salt according to claim 4 , having a diffraction peak at a diffraction angle 2θ±0.2° of 9.9° in powder X-ray diffraction.

7. A pharmaceutical composition comprising the salt according to claim 1 as an active ingredient.

8. The crystal of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one monomaleate salt according to claim 5 , having diffraction peaks at diffraction angles 2θ±0.2° of 9.1°, 10.1° and 11.1° in powder X-ray diffraction.

9. The crystal of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one monomaleate salt according to claim 5 , having peaks at chemical shifts, ±0.5 ppm of 13.3, 61.9, 114.3, 138.9 and 172.0 in a 13 C solid-state NMR spectrum.

10. The crystal of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo [4,3-c]quinolin-4(5H)-one monobenzenesulfonate salt according to claim 6 , having diffraction peaks at diffraction angles 2θ±0.2° of 9.9°, 13.7° and 14.6° in powder X-ray diffraction.

11. The crystal of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one monobenzenesulfonate salt according to claim 6 , having peaks at chemical shifts, ±0.5 ppm of 16.8, 67.9, 114.0, 137.7 and 160.7 in a 13 C solid-state NMR spectrum.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Ozaki Shunsuke

Classifications

• A61P43/00

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

• C07C309/29

  of non-condensed six-membered aromatic rings · 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

• C07B2200/13

  Crystalline forms, e.g. polymorphs · 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