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

A trans-cyclohexane amide compound and its application

A compound and reaction technology, applied in the field of drugs related to thrombosis, can solve problems such as high bleeding risk

Inactive Publication Date: 2016-08-17
ZHEJIANG PHARMA COLLEGE
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of these drugs is the greater risk of bleeding

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
  • A trans-cyclohexane amide compound and its application
  • A trans-cyclohexane amide compound and its application
  • A trans-cyclohexane amide compound and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] The preparation of embodiment 1 compound I of the present invention

[0022]

[0023] In a 100mL round bottom flask, add 1.84g (10mmol) compound II and 10mL redistilled SOCl 2 , and then heated to reflux for 3 hours with stirring.

[0024] The reaction mixture was evaporated under reduced pressure to remove excess SOCl 2 , the residue II-C was dissolved in 20 mL of dry dichloromethane, the resulting mixture was stirred under cooling in an ice-water bath, and slowly added dropwise from 1.62 g (10 mmol) III and 3.04 g (30 mmol) of triethylamine in 5 mL of dry dichloromethane The solution made of methyl chloride was stirred overnight at room temperature. TLC showed the reaction was complete.

[0025] The reaction mixture was poured into ice water, stirred, extracted with 50mL×3 dichloromethane, combined and extracted organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated on a rotary evaporator, and the obt...

Embodiment 2

[0026] The preparation of embodiment 2 comparative compound 1-2

[0027] In order to further compare the drug efficacy of this compound, the present invention records the following formula comparative compound I-2 (new compound, not yet disclosed) and its preparation method and pharmacological data:

[0028]

[0029] Its preparation method is as follows:

[0030]

[0031] In a 100mL round bottom flask, add 1.84g (10mmol) compound II, 1.26g (10mmol) compound III-2 and 20mL dry THF, the resulting mixture was stirred under ice-water bath cooling, after adding 2.48g (12mmol) DCC, Stirring was continued overnight at room temperature. TLC showed the reaction was complete.

[0032] The reaction mixture was poured into ice water, stirred, extracted with 50mL×3 dichloromethane, combined and extracted organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated on a rotary evaporator, and the obtained residue column Purifi...

Embodiment 3

[0033] Example 3 In vitro Platelet Aggregation Inhibition Test

[0034] Pharmacological tests of substances were performed in TRAP (thrombin receptor activating peptide)-induced platelet aggregation in 96-well plates. Add 3.13% sodium citrate solution to the syringe in advance, then draw 20mL of blood from healthy volunteers, centrifuge at 1500g for 20 minutes, separate the platelet-rich plasma (PRP) and wash it with 1μL PGE1 solution (500μg / mL ethanol solution) / mL PRP for treatment. After incubation at room temperature for 5 minutes, they were centrifuged at 1200 g for 20 minutes to remove leukocytes. Transfer the leukocyte-free PRP to 15 mL PP tubes in batches at 5 mL / portion, and centrifuge at 3600 g to pellet the platelets. Then, decant the upper plasma layer and resuspend the platelet pellet from 5 mL of PRP in 1 mL of Tyrode (120 mM NaCl, 2.6 mM KCl, 12 mM NaHCO 3 , 0.39 mM NaH 2 PO 4 , 10 mM HEPES, 0.35% BSA, 5.5 mM glucose, pH=7.4), and adjusted to a platelet coun...

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 relates to the field of medicines related to thrombotic diseases and in particular relates to PAR-1 (protease activated receptors-1) antagonists containing trans-cyclohexane amide structures shown in a formula (I) and an application of the PAR-1 antagonists to preparation of medicines for treating thrombotic diseases.

Description

technical field [0001] The invention relates to the field of drugs related to thrombosis diseases. Specifically, the present invention relates to a PAR-1 antagonist containing a trans-cyclohexyl amide structure that has a therapeutic effect on thrombotic diseases, and its application in the preparation of drugs for treating thrombotic diseases. Background technique [0002] Protease Activated Acceptor-1 (PAR-1) is a new target of anti-platelet antithrombotic drugs discovered recently. Protease-activated receptor 1 is also called thrombin receptor. After thrombin is activated by the coagulation chain, it acts on platelets through PAR-1 receptors to activate platelets, causing platelet aggregation and causing thrombus and coagulation. The thrombus induced by PAR-1 is rich in platelet components, which is the main cause of arterial thrombus. PAR-1 antagonists can block thrombin from activating platelets, thereby blocking arterial thrombosis, and can be used to treat acute cor...

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 Patents(China)
IPC IPC(8): C07D295/185A61K31/495A61P7/02
CPCC07D295/185
Inventor 郭章华
Owner ZHEJIANG PHARMA COLLEGE
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