Citric acid derivative

Patent metadata

Field	Value
Publication number	US-10494362-B2
Application number	US-201615770300-A
Country	US
Kind code	B2
Filing date	Nov 1, 2016
Priority date	Nov 2, 2015
Publication date	Dec 3, 2019
Grant date	Dec 3, 2019

Abstract

Compounds (citric acid derivatives) represented by formulas (1) and (2) below are novel compounds having an inhibitory effect against liver disorder and can be used as liver disorder inhibitors and food additives (wherein R 1 represents a C1 to C3 alkyl group optionally having a carboxyl group or a hydroxyl group, and R 2 represents a hydrogen atom, or R 1 and R 2 optionally form a cyclic structure together to represent a C2 to C3 alkylene chain).

First claim

The invention claimed is:

1. A compound represented by formula (1):

wherein R 1 represents a methyl group having a carboxyl group, and R 2 represents a hydrogen atom, or R 1 and R 2 optionally form a cyclic structure together to represent a C2 to C3 alkylene chain.

2. The compound according to claim 1 , wherein
the compound represented by formula (1) is represented by the following structures:

3. A method for inhibiting liver disorder comprising:
administering a compound represented by formula (1):

wherein R 1 represents a methyl group having a carboxyl group, and R 2 represents a hydrogen atom, or R 1 and R 2 optionally form a cyclic structure together to represent a C2 to C3 alkylene chain to a subject having liver disorder.

4. The method for inhibiting liver disorder according to claim 3 , wherein the liver disorder is nonalcoholic steatohepatitis (NASH).

5. A method for synthesizing a compound represented by formula (1), comprising:
reacting by heating a mixture of citric acid and an amine compound represented by formula (3):

wherein R 1 represents a methyl group having a carboxyl group, and R 2 represents a hydrogen atom, or R 1 and R 2 optionally form a cyclic structure together to represent a C2 to C3 alkylene chain.

6. The method according to claim 5 , wherein
the mixture of the citric acid and the amine compound represented by formula (3) is reacted at 100 to 130° C. for 30 minutes to 300 minutes.

7. The method according to claim 5 , wherein
a mixing ratio of the citric acid to the amine compound represented by formula (3) (concentration of the citric acid:concentration of the amine compound represented by formula (3)) is 75:1 to 12:10.

Assignees

• Adabio Co Ltd
• Otsuka Pharma Factory Inc

Inventors

• Hiraishi Katsuya
• Jimma Fumie
• Soma Hiroyuki
• Adachi Taro
• Adachi Masakazu
• Yamaoka Ippei
• Kagawa Tomohiro

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• C07D207/416 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms · CPC title