Adamantane derivative compound

Patent metadata

Field	Value
Publication number	US-10696611-B2
Application number	US-201515506972-A
Country	US
Kind code	B2
Filing date	Aug 24, 2015
Priority date	Aug 29, 2014
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

Disclosed is a novel adamantine derivative compound, an isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or a solvate thereof. Also disclosed is a method for preparing a novel adamantine derivative compound, an isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or a solvate thereof. The novel adamantane derivative compound or the like has an excellent anti-androgenic effect.

First claim

The invention claimed is:

1. A compound represented by the following Chemical Formula 1, an isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or a solvate thereof:

wherein X is —NHCO— or —CONH—,
each of R 1 and R 2 is independently substituted, R 1 is selected from the group consisting of hydrogen, halogen, NO 2 , C 1 -C 6 alkoxy, CN, CO 2 Me, CO 2 H and NH 2 ,
R 2 is selected from the group consisting of hydrogen, C 1 -C 6 alkoxy, C 1 -C 6 alkyl and halogen,
or
R 1 and R 2 are linked to each other to form a cyclic carbon chain optionally containing a hetero atom, wherein the cyclic carbon chain is selected from the group consisting of C 2 -C 18 cycloalkyl; C 4 -C 18 aryl; C 2 -C 18 heterocycloalkyl in which at least one carbon is substituted with at least one hetero atom selected from nitrogen, oxygen and sulfur; and C 4 -C 18 heteroaryl in which at least one carbon is substituted with at least one hetero atom selected from nitrogen, oxygen and sulfur;
R 3 is selected from the group consisting of hydrogen, C 1 -C 6 alkoxy and halogen, wherein the compound is selected from the group consisting of:
adamantan-1-carboxylic acid-(3-methyl-4-nitrophenyl)amide;
adamantan-1-carboxylic acid-(3-methoxy-4-nitrophenyl)amide;
adamantan-1-carboxylic acid-(3-chloro-4-nitrophenyl)amide;
adamantan-1-carboxylic acid-(4-cyano-3-methoxy-phenyl)amide;
adamantan-1-carboxylic acid-(4-cyano-2-chloro-phenyl)amide;
N-adamantan-1-yl-N-(4-nitro-3-methoxy-phenyl)-acetamide,
N-adamantan-1-yl-N-(4-nitro-3-chloro-phenyl)-acetamide,
adamantan-1-carboxylic acid (4-fluoro-3-methoxyphenyl)amide;
adamantan-1-carboxylic acid benzoxazol-6-yl amide;
adamantan-1-carboxylic acid (4-bromo-3-methoxyphenyl)amide;
4-[(adamantan-1-carbonyl)-amino]2-methoxy-benzoic acid methylester;
adamantan-1-carboxylic acid (5,6,7,8-tetrahydronaphthalen-2-yl)amide;
and
4-[(adamantan-1-carbonyl)-amino]-2-methoxybenzoic acid.

2. The compound according to claim 1 which is adamantan-1-carboxylic acid-(3-methoxy-4-nitrophenyl)amide.

3. A method for inhibiting androgen of a subject, wherein the method comprises administering an effective amount of the compound, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof according to claim 1 to the subject in need thereof.

4. The method according to claim 3 , wherein the compound, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof, stimulates hair growth.

5. The method according to claim 3 , wherein the compound, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof, inhibits sebum production.

6. A composition comprising the compound, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof as defined in claim 1 .

7. The composition according to claim 6 , which comprises the compound, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof as defined in claim 1 , in an amount of 0.01 wt %-20 wt % based on the total weight of the composition.

8. The composition according to claim 6 , which is a skin application composition.

9. The composition according to claim 6 , which is an anti-androgenic composition.

10. The composition according to claim 6 , which is a composition for stimulating hair growth.

11. The composition according to claim 6 , which is an anti-sebum composition.

12. A method for preparing the compound, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof as defined in claim 1 , the method comprising:
reacting a compound represented by the following Chemical Formula 2 or 3 with a benzoic acid salt derivative or phenylamine derivative in the presence of a base:

wherein the benzoic acid salt derivative is selected from the group consisting of 3-methoxy-4-nitrobenzoyl chloride, and 3-chloro-4-nitrobenzoyl chloride, and
wherein the phenylamine derivative is selected from the group consisting of 3-methyl-4-nitroaniline, 3-methoxy-4-nitroaniline, 3-chloro-4-nitroaniline, 3-methoxy-4-cyanoaniline, 2-chloro-4-cyanoaniline, 6-aminobenzothiazole, 4-fluoro-3-methoxyaniline, 4-bromo-3-methoxyaniline, 3-methoxy-4-methoxycarbonylaniline, and 5,6,7,8-tetrahydronaphthylamine.

Assignees

• Amorepacific Corp

Inventors

• Joo Yung Hyup
• Shin Song Seok
• Woo Byoung Young
• Baek Heung Soo
• Hong Yong Deog
• Shin Hong-Ju
• Jeong Yeon Su
• Lee Jon Hwan

Classifications

• A61K8/42 Primary

  Amides · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• C07C231/02

  from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines · CPC title

• A61K31/166

  having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol · CPC title

• A61P17/14

  for baldness or alopecia · CPC title