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

Trans-cyclohexane amides containing nitrile phenyl groups and uses thereof

A technology of compounds and uses, which is applied in the field of drugs related to thrombosis diseases, and 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
  • Trans-cyclohexane amides containing nitrile phenyl groups and uses thereof
  • Trans-cyclohexane amides containing nitrile phenyl groups and uses thereof
  • Trans-cyclohexane amides containing nitrile phenyl groups and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Embodiment 1 Preparation of Compound I of the present invention

[0023]

[0024] 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.

[0025] 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 1.87 g (10 mmol) III and 3.04 g (30 mmol) of triethylamine dissolved in 5 mL of dry dichloromethane The solution made of methyl chloride was stirred overnight at room temperature. TLC showed the reaction was complete.

[0026] 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 t...

Embodiment 2

[0027] Embodiment 2 Preparation of comparative compound 1-2

[0028] 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:

[0029]

[0030] Its preparation method is as follows:

[0031]

[0032] 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.

[0033] 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 2.07 g (10 mmol) III-2 and 3.04 g (30 mmol) of triethylamine dissolved in 5 mL of dry solution in dichloromethane and continued to stir overnight at room temperature. TLC showed the reaction was complete. ...

Embodiment 3

[0035] Example 3 In vitro platelet aggregation inhibition test

[0036] Pharmacological tests of substances were performed in TRAP (thrombin receptor activating peptide)-induced platelet aggregation in 96-well plates. 3.13% sodium citrate solution was pre-added in the syringe, and then 20 mL of blood from healthy volunteers was drawn in, centrifuged at 1500 g for 20 minutes, and the platelet-rich plasma (PRP) was separated and mixed with 1 / μL PGE1 solution (500 μg / mL of ethanol solution) / mL of 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 , 0.39mM NaH 2 PO 4 , 10 mM HEPES, 0.35% BSA, 5.5 mM glucose, pH=7.4), an...

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 medicines associated with thrombotic diseases, and particularly relates to a nitrile group and phenyl group-containing PAR-1 (pretease activated receptor-1) antagonist and application of antagonist in preparation of medicines for treating thrombotic diseases, wherein the nitrile group and phenyl group-containing PAR-1 antagonist has a structure of a formula (I) as shown in the specification.

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 with a trans-cyclohexyl amide structure containing a nitrile phenyl group, which 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 ...

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