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

Therapeutic compounds

A technology selected from, alkyl, applied in the field of preparing these compounds, can solve the problem of patients prone to liver cirrhosis and liver-related complications, etc.

Pending Publication Date: 2021-06-18
C4X DISCOVERY
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although all subtypes of NAFLD increase the risk of cardiovascular events and death, NASH (nonalcoholic steatohepatitis) is the main diagnostic subtype of NAFLD, predisposing patients to cirrhosis and liver-related complications

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
  • Therapeutic compounds
  • Therapeutic compounds
  • Therapeutic compounds

Examples

Experimental program
Comparison scheme
Effect test

example

[0763] General procedure:

[0764] Methods for preparing compounds of the present invention are shown in the examples below. Starting materials are prepared according to procedures known in the art or as shown herein, or are commercially available. Commercial reagents were used without further purification. The reaction is carried out at ambient temperature, typically 18°C ​​to 27°C, excluding the reaction temperature.

[0765] The compounds described in the present invention are 1 In the case of H NMR spectral characterization, spectra were recorded on 500 MHz Bruker, 400 MHz Bruker, 250 MHz Bruker, 300 MHz JEOL, or 400 MHz JEOL instruments. Spectra were recorded at ambient temperature when temperature was not included. Chemical shift values ​​are expressed in parts per million (ppm). In cases where NMR spectra are complicated by the presence of tautomers, approximate partial integration of the signal is reported, or only the characterization of the major isomer is rep...

example 1

[1091] Example 1: (1S,2R)-2-((S)-1-((1,3-dioxoisoindolin-2-yl)methyl)-8-(2-(5-methyl) different oxazole-3-carboxamide)ethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclohexanecarboxylic acid

[1092]

[1093] Step a. To a stirred suspension of intermediate 11 (0.45 g, 1.1 mmol) and cesium carbonate (1.44 g, 4.4 mmol) in DMF (6 mL) at room temperature was added N-(2-chloroethyl)-bis Benzylamine hydrochloride (0.46 g, 1.5 mmol, CAS: 55-43-6) and the reaction was heated at 100 °C for 18 hours. The reaction mixture was concentrated in vacuo, diluted with water (25 mL), and extracted with DCM (25 mL). The organic layer was further washed with water (50 mL), washed with Na 2 SO 4 Dry and concentrate in vacuo to give tert-butyl (S)-8-(2-(dibenzylamino)ethoxy)-1-((1,3-dioxoisoindolin-2-yl) Methyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.10 g, assumed quantitative). 1 H NMR (400MHz, DMSO-d 6 , observed rotamers, all reported) δ 7.98-7.75 (m, 4H), 7.44-7.03 (m, 11H...

example 2

[1099] Example 2: (1S,2R)-2-((S)-8-(2-(benzo[d]oxazole-2-carboxamide)ethoxy)-1-((1,3-dioxo (isoindolin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclohexane-1-carboxylic acid

[1100]

[1101] Step a. Benzyl(1S,2R)-2-(((S) was prepared from Intermediate 10 (350 mg, 1.14 mmol) and Intermediate 26 (351 mg, 1.25 mmol) using a procedure similar to that described in Example 1, Step e. )-1-((1,3-dioxoisoindolin-2-yl)methyl)-8-hydroxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclohexane Alkane-1-carboxylate (370 mg, 59%). LCMS (Method 4a): 2.86 min, 553.4 [M+H] + . 1H NMR (400MHz, DMSO-d 6) 9.86(br s, 1H), 7.86-7.79(m, 4H), 7.19-7.00(m, 5H), 6.73(d, 1H), 6.60(d, 1H), 5.98(dd, 1H), 4.77(q ,2H),4.22(dd,1H),3.80(d,1H),3.75-3.60(m,2H),3.29-3.24(m,1H),2.73-2.69(m,1H),2.40(dt,1H ), 1.84(q, 1H), 1.68-1.60(m, 1H), 1.50(d, 1H), 1.36-1.23(m, 3H), 1.00-0.76(m, 3H), 0.15(q, 1H).

[1102] Step b. Benzyl (1S,2R)-2-(((S)-) was prepared from the above intermediate and tert...

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

PropertyMeasurementUnit
thicknessaaaaaaaaaa
Login to View More

Abstract

The present invention relates to compounds that are Nrf2 activators. The compounds have the structural formula I defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with Nrf2 activation.

Description

[0001] introduction [0002] The present invention relates to tetrahydroisoquinoline compounds. More specifically, the present invention relates to tetrahydroisoquinoline compounds that are Nrf2 activators. The present invention also relates to methods for preparing these compounds, to pharmaceutical compositions comprising these compounds, and to their use in the treatment of diseases or disorders associated with Nrf2 activation and / or inhibition of Keap1-Nrf2 protein-protein interactions . Background technique [0003] Nuclear factor erythroid 2-related factor 2 (Nrf2) is a basic leucine zipper (bZIP) transcription factor and a member of the Cap'n'Collar (CNC) transcription factor family. It is a key controller of the inducible cellular defense system, mediating the expression of more than 100 genes associated with oxidative stress, including phase I and II detoxification enzymes and antioxidant proteins. These genes contain antioxidant response elements (AREs) in their p...

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): C07D403/14C07D413/14C07D417/14C07D471/04A61K31/4725
CPCC07D403/14C07D417/14C07D471/04C07D413/14A61K31/4725C07D401/14C07D405/14C07D487/04C07D498/04
Inventor 艾玛·路易丝·布莱尼邓肯·詹姆斯·克里克西蒙·罗丝·克伦普勒乔治·海德凯茜·路易丝·卢卡斯巴里·菲利普·马丁尼克·查尔斯·雷艾琳·玛丽·苏华德大卫·加雷思·埃文斯露西尔·勒博泽克索斯藤·诺瓦克迈克尔·杰弗里·尼尔·拉塞尔叶秀权法比安·珍·吉斯兰·鲁塞尔圣吉特·辛格·塞米
Owner C4X DISCOVERY
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