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

Heterocyclic compound and application thereof and pharmaceutical composition containing heterocyclic compound

A technology of heterocyclic compounds and pharmacy, applied in the direction of active ingredients of heterocyclic compounds, drug combinations, antipyretics, etc., can solve the problem of single structure of ATX inhibitors

Active Publication Date: 2019-08-23
SUZHOU SINOVENT PHARMA CO LTD
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is that the existing ATX inhibitors have relatively simple structures and other defects. Therefore, the present invention provides a heterocyclic compound, its application and a pharmaceutical composition containing it

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
  • Heterocyclic compound and application thereof and pharmaceutical composition containing heterocyclic compound
  • Heterocyclic compound and application thereof and pharmaceutical composition containing heterocyclic compound
  • Heterocyclic compound and application thereof and pharmaceutical composition containing heterocyclic compound

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0824] Preparation Example 1 Intermediate Synthetic Method

[0825]

[0826] Step 1, 2-amino-4-(3,4-difluorophenyl)thiazole-5-carbonitrile

[0827] To a solution of 3-(3,4-difluorophenyl)-3-oxopropionitrile (1.38 g, 7.63 mmol) in ethanol (18 mL) was added pyridine (0.60 g, 7.63 mmol). The reaction was stirred at 70°C for 15 minutes, then cooled to room temperature. Thiourea (1.18g, 215.52mmol) and iodine (1.96g, 7.63mmol) were mixed in ethanol (18mL), and the mixture was slowly added dropwise to the above solution, and stirred at room temperature for 1 hour. The reaction was quenched by adding cold sodium thiosulfate solution (10 mL). After filtering and washing the filter cake with water, the filter cake was dried to give 2-amino-4-(3,4-fluorophenyl)thiazole-5-carbonitrile as an off-white solid (1.50 g, 82.9%). 1H NMR (400MHz, DMSO-d6) δ8.28(s, 2H), 7.89–7.83(m,1H), 7.82–7.78(m,1H), 7.65-7.58(m,1H)

[0828] Step 2, 2-Chloro-4-(3,4-difluorophenyl)thiazole-5-carbonitrile...

Embodiment 1

[0845] Example 1S-0021: 2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazine-1- Base) imidazo[1,2-a]pyrimidin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile

[0846]

[0847] Step 1: 2-Chloro-1-(3-hydroxyazetidin-1-yl)acetyl

[0848] To an aqueous solution (8 mL) of potassium carbonate (3 g, 22 mmol) was added 3-hydroxyazetidine hydrochloride (1.1 g, 10 mmol). The reaction solution was stirred at room temperature for 10 minutes, then dichloromethane was added to dilute (8 mL) and the reaction solution was cooled to 0°C, and 2-chloroacetyl chloride (1.3 g, 12 mmol) was slowly added dropwise. The reaction solution was stirred at room temperature for 2 hours, filtered, the organic phase was separated, and the aqueous phase was extracted with methanol / ethyl acetate mixture (1 / 1) (20 mL x 6). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was resuspended in acetone (50 mL) and stirred ...

Embodiment 2

[0867] Example 2S-0022: 2-((2-ethyl-5-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazine-1- Base)-7-methyl-2H-indazol-3-yl)(methyl)amine)-4-(4-fluorophenyl)thiazole-5-carbonitrile

[0868]

[0869] Step 1: 5-Bromo-2-fluoro-3-methylbenzonitrile

[0870] Add iodine (11.67g, 46.3mmol) to a mixture of 5-bromo-2-fluoro-3-methylbenzaldehyde (5g, 23.1mmol) in tetrahydrofuran (20mL) and ammonia water (20mL), and the reaction solution was heated at room temperature Stir for 16 hours. Sodium bisulfite solution (20 mL) was added to the reaction solution to quench the reaction, and then extracted with ethyl acetate (50×2 mL). The organic phases were combined, washed with saturated brine (10 mL x 2), dried over anhydrous sodium sulfate, filtered and concentrated to give 5-bromo-2-fluoro-3-methylbenzonitrile as a white solid (5 g, 98%) , used directly in the next reaction without further purification. 1 H NMR (400MHz, CDCl 3 )δ7.55-7.59(m,2H),2.32(s,3H).

[0871] Step 2: 5-Bromo-...

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 discloses a heterocyclic compound and application thereof and a pharmaceutical composition containing the heterocyclic compound. The invention provides a heterocyclic compound shown in formula I or a pharmaceutically acceptable salt thereof. The compound has novel structure and better ATX inhibitory activity.

Description

technical field [0001] The invention provides a heterocyclic compound, its application and a pharmaceutical composition containing it. Background technique [0002] Autotaxin (ATX, also known as ENPP2 [external nucleotide pyrophosphatase / phosphodiesterase 2] or lysophospholipase D) is an enzyme that converts lysophosphatidylcholine (LPC) into the biologically active phospholipid derivative lysophospholipid Acid (LPA) secreted lysophospholipase D (lysoPLD). LPA and through specific G protein-coupled receptors (LPA 1-6 ) signal to exert its biological activity. Since the ATX / LPA axis is involved in many physiological and pathophysiological processes, it has attracted considerable interest from the pharmaceutical industry. LPA and LPA receptors are involved in many diseases such as fibrotic diseases (such as idiopathic pulmonary fibrosis, IPF), proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative...

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): C07D417/14C07D401/14C07D403/14C07D471/04C07D487/04C07D491/048A61K31/496A61K31/519A61K31/5025A61K31/53A61K31/506A61P1/16A61P11/00A61P35/00A61P29/00A61P19/02A61P37/02A61P9/00A61P25/28A61P17/00A61P9/14
CPCC07D417/14C07D401/14C07D403/14C07D471/04C07D487/04C07D491/048A61P1/16A61P11/00A61P35/00A61P29/00A61P19/02A61P37/02A61P9/00A61P25/28A61P17/00A61P9/14A61K31/496A61K31/519A61P37/00C07D495/04A61K45/06A61K31/4418A61K2300/00
Inventor 胡永韩吴冬冬彭薇李昕胡凡黄彬朱金莲吴予川
Owner SUZHOU SINOVENT PHARMA CO LTD
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