Novel salt of terphenyl compound

Patent metadata

Field	Value
Publication number	US-2022411368-A1
Application number	US-202017775795-A
Country	US
Kind code	A1
Filing date	Nov 13, 2020
Priority date	Nov 13, 2019
Publication date	Dec 29, 2022
Grant date	—

Abstract

A benzoic acid salt of 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile is provided. A sorbic acid salt of 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile is also provided.

First claim

1 . A benzoic acid salt of 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile.

2 . The benzoic acid salt according to claim 1 , wherein the salt comprises a crystal.

3 . The benzoic acid salt according to claim 2 , wherein the crystal has a powder X-ray diffraction spectrum having at least two peaks of diffraction angles (2θ±0.2°) selected from the group consisting of 15.3°, 16.2°, 17.8°, 21.4° and 25.5°.

4 . (canceled)

5 . The benzoic acid salt according to claim 2 , wherein the crystal has a peak temperature in a differential scanning calorie (DSC) curve with an endothermic peak in the range from 188° C. to 198° C.

6 . The benzoic acid salt according to claim 2 , wherein the crystal has a powder X-ray diffraction spectrum of FIG. 1 .

7 . A sorbic acid salt of 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile.

8 . The sorbic acid salt according to claim 7 , wherein the salt comprises a crystal.

9 . The sorbic acid salt according to claim 8 , wherein the crystal has a powder X-ray diffraction spectrum having at least two peaks of diffraction angles (2θ±0.2°) selected from the group consisting of 5.5°, 10.9°, 16.2°, 17.2°, 20.3° and 24.4°.

10 . (canceled)

11 . The sorbic acid salt according to claim 8 , wherein the crystal has a peak temperature in a differential scanning calorie (DSC) curve with an endothermic peak in the range from 142° C. to 152° C.

12 . The sorbic acid salt according to claim 8 , wherein the crystal fumarate has a powder X-ray diffraction spectrum of FIG. 13 .

13 . An LSD1 inhibitor comprising the salt according to claim 1 , as an active ingredient.

14 . A pharmaceutical composition comprising the salt according to claim 1 .

15 . The pharmaceutical composition according to claim 14 , wherein the composition is a pharmaceutical composition for preventing or treating an LSD1-related disease or disorder.

16 . The pharmaceutical composition according to claim 14 , which is an orally administered composition.

17 . An antitumor agent comprising the salt according to claim 1 , as an active ingredient.

18 . A method of treating an LSD1-related disease or disorder in a patient in need, the method comprising administering an effective amount of the salt according to claim 1 to the patient.

19 . (canceled)

20 . (canceled)

21 . A production method of a benzoic acid salt of 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile, the method comprising:
reacting 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile with a benzoic acid.

22 . A production method of a sorbic acid salt of 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile, the method comprising:
reacting 4-[5-[(3S)-3-aminopyrrolidine-1-carbonyl]-2-[2-fluoro-4-(2-hydroxy-2-methyl-propyl)phenyl]phenyl]-2-fluoro-benzonitrile with a sorbic acid.

23 . An LSD1 inhibitor comprising the salt according to claim 7 as an active ingredient.

24 . A pharmaceutical composition comprising the salt according to claim 7 .

25 . An antitumor agent comprising the salt according to claim 7 as an active ingredient.

26 . A method of treating an LSD1-related disease or disorder in a patient in need, the method comprising administering an effective amount of the salt according to claim 7 to the patient.

Assignees

• Taiho Pharmaceutical Co Ltd

Inventors

• Nakamura Hiroyuki

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/203

  Retinoic acids {; Salts thereof} · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K31/40 Primary

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• C07D207/14 Primary

  Nitrogen atoms not forming part of a nitro radical · CPC title