Benzoic acid amide compound

Patent metadata

Field	Value
Publication number	US-10385011-B2
Application number	US-201615561585-A
Country	US
Kind code	B2
Filing date	Mar 30, 2016
Priority date	Mar 31, 2015
Publication date	Aug 20, 2019
Grant date	Aug 20, 2019

Abstract

Disclosed are a novel benzoic acid amide derivative compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof. The novel compound and the like inhibit melanin production, prevent tyrosinase activity, and have an excellent skin whitening effect.

First claim

The invention claimed is:

1. A compound of the following chemical formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof:

wherein R 1 of Chemical Formula 1 is selected from the group consisting of halogen, C 1 -C 5 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkenyl, and C 6 -C 18 aryl group, wherein the aryl group is unsubstituted or substituted with one or more selected from the group consisting of halogen, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, methylenedioxy, and nitro groups.

2. The compound, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof according to claim 1 , wherein the compound is selected from the group consisting of N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-methyl-benzoic acid amide, 5-bromo-N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-benzoic acid amide, 5-tert-butyl-N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-benzoic acid amide, N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-phenyl-benzoic acid amide, N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-(4-fluoro-phenyl)-benzoic acid amide, N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-(4-methoxy-phenyl)-benzoic acid amide, 5-benzo[1,3]dioxol-5-yl-N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-benzoic acid amide, 5-cyclohexene-1-yl-N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-benzoic acid amide, N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-(3,5-dimethyl-phenyl)-benzoic acid amide, 5-cyclohexyl-N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-benzoic acid amide, N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-(3,4-difluoro-phenyl)-benzoic acid amide, and N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-(3-nitro-phenyl)-benzoic acid amide.

3. The compound, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof according to claim 1 , wherein the compound is N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy-5-(3,5-dimethyl-phenyl)-benzoic acid amide.

4. A method of preparing the compound of chemical formula 1, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof according to claim 1 , wherein the method comprises a first step of reacting a benzoic acid derivative of the following chemical formula 2 and a hydroxyl group substituted alkyl-phenyl amine as reactants:

wherein R 1 of chemical formula 1 is selected from the group consisting of halogen, C 1 -C 5 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkenyl and C 6 -C 18 aryl group, wherein the aryl group is unsubstituted or substituted with one or more selected from the group consisting of halogen, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, methylenedioxy, and nitro groups; and

wherein R of chemical formula 2 is selected from the group consisting of halogen, C 1 -C 5 alkyl, C 3 -C 6 cycloalkyl, and C 3 -C 6 cycloalkenyl; wherein the first step is performed in presence of N-hydroxysuccinimide and N,N′-dicyclohexylcarbodiimide (DCC).

5. The method of preparing the compound of chemical formula 1 according to claim 4 , wherein the R of chemical formula 2 is halogen.

6. The method of preparing the compound of chemical formula 1 according to claim 5 , wherein the method further comprises a second step of reacting the resulting bromo benzoic acid amide derivative and arylboronic acid, in a case where the R of chemical formula 2 is bromine group to form a bromo benzoic acid derivative.

7. The method of preparing the compound of chemical formula 1 according to claim 6 , wherein the second step is performed in presence of a palladium catalyst under base condition.

8. The method of preparing the compound of chemical formula 1 according to claim 6 , wherein the aryl bromic acid is unsubstituted or substituted with one or more selected from the group consisting of halogen, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, methylenedioxy, and nitro groups.

9. A method for skin whitening comprising administering the compound according to claim 1 , the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof to a subject in need thereof.

10. The method for skin whitening according to claim 9 ,
wherein the compound, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof is contained in a composition in a concentration of 0.01 wt % to 20 wt % based on total weight of the composition.

11. The method for skin whitening according to claim 9 ,
wherein the compound, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof inhibits melanin production.

12. The method for skin whitening according to claim 9 , wherein the compound, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof inhibits tyrosinase activity.

13. The method according to claim 9 , wherein the compound, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof is one for external application to skin.

14. The method according to claim 9 , wherein the compound, the isomer thereof, the pharmaceutically acceptable salt thereof, the hydrate thereof, or the solvate thereof is one for a cosmetic composition, a pharmaceutical composition, or health food composition.

Assignees

• Amorepacific Corp

Inventors

• Joo Yung Hyup
• Choi Soo Jeong
• Baek Heung Soo
• Lee Chang Seok
• Kim Jeong Hwan
• Kim Yongjin
• Shin Hong-Ju
• Rho Ho Sik
• Shin Song Seok
• Lee Jon Hwan

Classifications

• A61P43/00

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

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61Q19/02

  for chemically bleaching or whitening the skin · CPC title

• A61K8/42

  Amides · 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