1-sulfonamido-4-aryloxy compounds, and preparation method and medicinal application thereof

Patent metadata

Field	Value
Publication number	US-10442759-B2
Application number	US-201615755356-A
Country	US
Kind code	B2
Filing date	Nov 25, 2016
Priority date	Jan 18, 2016
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

Compounds of formula (I) having 1-sulfonamido-4-aryloxy as a basic backbone. A preliminary activity test showed that the compounds provide excellent interference of a binding of Nrf2 by Keap1, thereby activating Nrf2. The compounds have a potential anti-inflammatory activity and can be used to treat a plurality of inflammation-associated diseases, including chronic obstructive pulmonary disease (COPD), Alzheimer's disease, Parkinson's disease, atherosclerosis, chronic kidney disease (CKD), diabetes, gastroenteritis, rheumatoid arthritis, and the like.

First claim

What is claimed is:

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

wherein R 1 represents 4-trifluoromethyl, 4-trifluoromethoxy, 4-nitro, 4-hydroxyl, 4-hydroxymethyl, 4-cyano, 4-amino, H, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 alkylamino, or C1-C3 amido;
R 2 represents 4-trifluoromethyl, 4-trifluoromethoxy, 4-nitro, 4-hydroxyl, 4-hydroxymethyl, 4-cyano, 4-amino, 4-morpholinylmethoxy, 4-morpholinylethoxy, 4-benzylmethoxy, 4-benzylethoxy, 4-benzylamino, H, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 alkylamino, or C1-C3 amido;
R 3 represents H, —CH 2 COOH,

or —CH 2 CONH 2 ;
p=1-3;
q=1-3; and
n=0-3.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 represents 4-methoxy, 4-bromo, 4-chloro, 4-fluoro, 2,4,6-trimethyl, 4-tert-butyl, 2,4,6-trimethoxy, 4-methyl, 3,4-dimethoxy, 4-acetamido or 4-trifluoromethyl.

3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 represents 4-methoxy, 4-ethoxy, 4-isopropoxy, 4-fluoro, 4-chloro, 4-bromo, 4-acetamido, 4-trifluoromethyl, 4-hydroxyl, 4-morpholinylmethoxy, 4-morpholinylethoxy, 4-amino, or 4-benzylamino.

4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3 represents —CH 2 COOH or

5. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein n represents 0 or 1.

6. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt is a sodium, potassium or calcium carboxylate of the compound of Formula (I).

7. A method for preparing the compound according to claim 1 , the method comprising:

wherein R 1 , R 2 , p, q and n are as defined in claim 1 , and R 3 is CH 2 COOH.

8. A pharmaceutical composition, comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

9. A method for preparing the compound according to claim 1 , the method comprising:

wherein R 1 , R 2 , p, q and n are as defined in claim 1 , and R 3 is H.

10. A method for preparing the compound according to claim 1 , the method comprising:

wherein R 1 , R 2 , p, q and n are as defined in claim 1 , and R 3 is

11. A method for preparing the compound according to claim 1 , the method comprising:

wherein R 1 , R 2 , p, q and n are as defined in claim 1 , and R 3 is

Assignees

• Univ China Pharma

Inventors

• You Qidong
• Jiang Zhengyu
• Lu Mengchen
• Chen Zhiyun
• Sun Haopeng
• Zhang Xiaojin
• Guo Xiaoke
• Xu Xiaoli

Classifications

• C07D257/04 Primary

  Five-membered rings · CPC title

• C07C311/46

  Y being a hydrogen or a carbon atom · CPC title

• C07C311/29

  having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07C303/38

  by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof · CPC title

• C07C311/21 Primary

  having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title