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

1,3-diaryl pyrazole PTP1B inhibitor containing carboxyalkyl rhodanine structure as well as preparation and application thereof

A technology of pyrazole and structural formula, applied in the field of 1,3-diarylpyrazole PTP1B inhibitors containing carboxyalkyl rhodanine structure and its preparation and application, can solve the adverse effect and limit the value of treatment Drugs, poor selectivity, etc.

Inactive Publication Date: 2019-05-21
YANBIAN UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is regrettable that these compounds themselves have a high negative charge, and they mainly exist in the form of negative ions in the organism, which is not conducive to permeating the cell membrane, resulting in poor bioavailability; some inhibitors are selective for different PTPases Not good, not conducive to effectively acting on specific PTPase targets
These factors limit their development as therapeutically valuable drugs

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
  • 1,3-diaryl pyrazole PTP1B inhibitor containing carboxyalkyl rhodanine structure as well as preparation and application thereof
  • 1,3-diaryl pyrazole PTP1B inhibitor containing carboxyalkyl rhodanine structure as well as preparation and application thereof
  • 1,3-diaryl pyrazole PTP1B inhibitor containing carboxyalkyl rhodanine structure as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: (Z)-2-(5-((3-(naphthalene-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thio-4 -Thiazolidinone-3-yl)acetic acid (6a) Dissolve glycine (10mmol, 0.75g) in 15mL water, add NaOH (0.8g, 20mmol), slowly add 0.6mL CS 2 (10 mmol), stirred at room temperature for 10 hours. Anhydrous sodium chloroacetate (0.82 g, 10 mmol) was added in batches to the reaction solution, and stirring was continued at room temperature for 3 hours. Add 6M HCl (30mL), N 2 Protection, stirring and reflux for 16 hours, cooling. The reaction solution was extracted with ethyl acetate (3*50mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was spin-dried to obtain a yellow-green oil. The crude product was subjected to silica gel column chromatography (eluent: dichloromethane: Methanol=20:1) to obtain 1.24 g of white solid (2a), with a yield of 65%.

[0023] Phenylhydrazine (0.57g, 5.3mmol) was dissolved in 20mL of absolute ethanol, 2'-napht...

Embodiment 2

[0026] Example 2: (Z)-2-(5-((3-(3-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thio-4 -Thiazolidinone-3-yl) acetic acid (6b) replaces 2'-naphthylophenone with 3-chloroacetophenone, and the others are the same as 6a to obtain compound 6b with a yield of 91%; m.p.313-315°C. IR (KBr)cm -1 : 3419(OH), 1707(C=O). 1 H NMR (DMSO-d 6 , 300MHz, ppm): δ8.84(s, 1H), 8.06 (d, J=8.1Hz, 2H), 7.74(s, 1H), 7.61-7.53(m, 6H), 7.43(t, J=7.35 Hz, 1H), 4.49(s, 2H). 13 C NMR (DMSO-d 6 , 75MHz, ppm): δ245.30, 192.60, 167.12, 166.25, 152.27, 138.53, 133.68, 133.15, 130.98, 129.80, 122.63, 119.47, 115.74, 109.53, 40.20, 38.94.MS6 m / z+ .Calcd. for C 21 h 14 ClN 3 o 3 S 2 : C, 55.32; H, 3.09; N, 9.22; S, 14.07.Found: C, 55.31; H, 3.07; N, 9.20; S, 14.08.

Embodiment 3

[0027] Example 3: (Z)-2-(5-((3-(3-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thio-4 -Thiazolidinone-3-yl)acetic acid (6c) replaced 2′-naphthophenone with 3-bromoacetophenone, and the others were the same as 6a to obtain compound 6c with a yield of 88%; m.p.315-317°C. IR (KBr)cm -1 : 3419(OH), 1707(C=O). 1 H NMR (DMSO-d 6 , 300MHz, ppm): δ8.83(s, 1H), 8.07 (d, J=7.6Hz, 2H), 7.87(d, J=1.6Hz, 1H), 7.74(m, 1H), 7.66(d, J=7.9Hz, 1H), 7.54(m, 4H), 7.43(t, J=7.4Hz, 1H), 4.35(s, 2H).MS m / z 501(M+1).Calcd.for C 21 h 14 BrN 3 o 3 S 2 : C, 50.41; H, 2.82; N, 8.40; S, 12.82.Found: C, 50.39; H, 2.80; N, 8.38; S, 12.81.

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 provides a novel 1,3-diaryl pyrazole compound containing a carboxyalkyl rhodanine structure or a pharmaceutically acceptable salt of the compound as a novel protein tyrosine phosphatase1B (PTP1B) inhibitor. Studies show that the inhibitor of this type can effectively inhibit PTP1B activity and can be used as an insulin sensitizer for preventing and / or treating related diseases withinsulin resistance mediated by PTP1B, especially type II diabetes and obesity. The invention also provides a preparation method of the inhibitor.

Description

technical field [0001] The present invention relates to a class of 1,3-diarylpyrazole compounds containing a carboxyalkyl rhodanine structure or a pharmaceutically acceptable salt thereof with PTP1B inhibitory activity, and also relates to a preparation method of the inhibitor. The sensitizer is used in the prevention, delay or treatment of diseases mediated by PTP1B, especially type II diabetes and obesity. Background technique [0002] Type II diabetes is a common metabolic disorder, characterized by peripheral insulin resistance, and at the molecular level, it is manifested as a loss of signal transduction after insulin binds to insulin receptors. The phosphorylation level of protein tyrosine is an important regulator of intracellular signal transduction, which is jointly regulated by protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP). Recent studies have found that protein tyrosine phosphatase 1B can specifically hydrolyze the phosphate group on phosph...

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
IPC IPC(8): C07D417/06A61K31/427A61P3/10A61P3/04
Inventor 孙良鹏朴虎日徐丽丽
Owner YANBIAN UNIV
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