Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Aromatic polycyclic carboxylic acid derivative

A kind of medicine and compound technology, applied in the field of aromatic polycyclic carboxylic acid derivatives

Active Publication Date: 2014-12-31
吉林升通化工有限公司 +3
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Diabetes with the same pathogenesis can be effectively treated by using GPR40 receptor agonists. So far, there is no officially marketed new drug targeting GPR40

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Aromatic polycyclic carboxylic acid derivative
  • Aromatic polycyclic carboxylic acid derivative
  • Aromatic polycyclic carboxylic acid derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0283] Example 12-(6-((2',6'-dimethyl-4'-(2-(methylsulfonylamino)ethoxy)-[1,1'-biphenyl]-3-yl )methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid synthesis (preparation of compound 1)

[0284]

[0285] (1) Preparation of 4-(chloromethyl)-7-hydroxyl-2H-benzopyran-2-one

[0286]

[0287] Resorcinol (27.5g, 250mmol) was dissolved in acetic acid (60mL) and heated to 50°C for later use, ethyl 4-chloroacetoacetate (20.5g, 125mmol) was dissolved in acetic acid (20mL) and cooled in an ice-water bath, and concentrated sulfuric acid was slowly added (10mL), then add the acetic acid solution of resorcinol in an ice-water bath, stir at room temperature for 1h, and then react at 60°C for 3 hours. After the reaction was complete, water (300 mL) was added, stirred at room temperature for 1 h, and filtered under reduced pressure. The obtained white solid was washed three times with water (100 mL), and dried to obtain the product (17.6 g, yield 67%).

[0288] (2) Preparation of 2-(6-hydro...

Embodiment 2

[0317] Example 22-(6-((4'-(2-(cyclopropylsulfonylamino)ethoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3 Preparation of -yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid (compound 2)

[0318]

[0319] (1) Preparation of 2-(4-bromo-3,5-dimethylphenoxy)ethylamine

[0320]

[0321] Dissolve tert-butyl 2-(4-bromo-3,5-dimethylphenoxy)ethylcarbamate (2.0 g, 5.8 mmol) in dichloromethane (20 mL) and add trifluoroacetic acid (10 mL) , stirred at room temperature for 2h. The solvent was distilled off under reduced pressure, saturated sodium bicarbonate solution was added, extracted with ethyl acetate (100mL×3), the organic phases were combined, washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain an oily product (1.36 g, yield 96%).

[0322] (2) Preparation of N-(2-(4-bromo-3,5-dimethylphenoxy)ethyl)cyclopropylsulfonamide

[0323]

[0324] Dissolve 2-(4-bromo-3,5-dimethylphen...

Embodiment 3

[0336]Example 32-(6-((4'-(2-((N,N-dimethylaminosulfonyl)amino)ethoxy)-2',6'-dimethyl-[1,1'- Preparation of biphenyl]-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid (compound 3)

[0337]

[0338] (1) Preparation of tert-butyl 2-(4-bromo-3,5-dimethylphenoxy)ethylcarbamate

[0339]

[0340] N-Boc ethanolamine (5.8g, 36mmol), 4-bromo-3,5-dimethylphenol (6.03g, 30mmol), and azodicarbonyldipiperidine (11.34g, 45mmol) were dissolved in tetrahydrofuran ( 300mL), add tri-n-butylphosphine (9.1g, 45mmol) under ice bath, rise to room temperature after dropwise addition, react for 16h, add petroleum ether (200mL), suction filter, filtrate is spin-dried, crude product is passed through silica gel column Chromatography (ethyl acetate / petroleum ether=0~1 / 20) separated the product as a colorless oil (8.0 g, yield 77%).

[0341] (2) Preparation of 2-(4-bromo-3,5-dimethylphenoxy)ethylamine

[0342]

[0343] Dissolve tert-butyl 2-(4-bromo-3,5-dimethylphenoxy)ethylcarbamate (2.5 ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention belongs to the field of medicine technology, and specifically relates to an aromatic polycyclic carboxylic acid derivative GPR40 receptor agonist with a general formula (I), a pharmaceutically acceptable salt thereof, and an ester or stereoisomer thereof, wherein R1, R2, R3, R4, R5 and X are as defined in the specification. The invention also relates to preparation methods of the compounds, pharmaceutical preparation and pharmaceutical composition, as well as application of the compound and the pharmaceutical composition as the GPR40 receptor agonist to preparation of drugs for prevention and / or treatment of diabetes.

Description

1. Technical field [0001] The invention belongs to the field of medical technology, and in particular relates to aromatic polycyclic carboxylic acid derivatives GPR40 receptor agonists, their pharmaceutically acceptable salts, their esters and their stereoisomers, their preparation methods, pharmaceutical preparations and The pharmaceutical composition, and the application of these compounds as GPR40 receptor agonists in the preparation of medicines for preventing and / or treating diabetes. 2. Background technology [0002] The latest research shows that the GPR40 receptor agonist compound is a new drug for the treatment of type II diabetes. Its effect of improving blood sugar control is similar to that of glimepiride, but the risk of causing hypoglycemia is significantly lower than the latter. [0003] Type II diabetes is the most common type of diabetes. About 150 million people in the United States currently suffer from diabetes, 90% of whom have type 2 diabetes. The deg...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/79C07D417/12A61K31/343A61K31/427A61K31/433A61P3/10
CPCC07D307/79C07D417/12
Inventor 吴永谦
Owner 吉林升通化工有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com