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

Alkoxypyridyl-containing trans-cyclohexane amide compound and application thereof

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

Inactive Publication Date: 2015-02-18
ZHEJIANG PHARMA COLLEGE
View PDF4 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
  • Alkoxypyridyl-containing trans-cyclohexane amide compound and application thereof
  • Alkoxypyridyl-containing trans-cyclohexane amide compound and application thereof
  • Alkoxypyridyl-containing trans-cyclohexane amide compound and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1 Preparation of Compound I-1

[0025]

[0026] Raw materials: commercially available or homemade.

[0027] In a 100mL round bottom flask, add 1.84g (10mmol) compound II, 1.93g (10mmol) compound III-1 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.

[0028] 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 Purified by chromatography to obtain product I-1, a pale yellow solid, ESI-MS, m / z=361 ([M+H] + ).

Embodiment 2-4

[0030] Referring to the method of Example 1, the following compounds with general formula I were synthesized.

[0031]

[0032]

Embodiment 5

[0033] Example 5 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. 3.13% sodium citrate solution was added to the syringe in advance, and then 20 mL of blood from healthy volunteers was drawn in, centrifuged at 1500 g for 20 minutes, platelet-rich plasma (PRP) was separated and mixed with 1 μL of PGE1 solution (500 μg / 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 , 0.39mM NaH 2 PO 4 , 10 mM HEPES, 0.35% BSA, 5.5 mM glucose, pH=7.4), and adj...

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 thrombotic disease related medicines. Specifically, the invention relates to a trans-cyclohexane amide structured PAR-1 antagonist containing structures, such as alkoxy substituted pyridyl and the like, a preparation method of the antagonist and application of the antagonist in preparation of medicines for treating thrombotic diseases, wherein R is selected from C1-C3 alkyl and C3-C5 cycloalkyl.

Description

technical field [0001] The invention relates to the field of drugs related to thrombosis diseases. Specifically, the present invention relates to a class of PAR-1 antagonists with a trans-cyclohexyl amide structure containing alkoxy-substituted pyridyl and other structures that have a therapeutic effect on thrombotic diseases, and a preparation method thereof, and a drug combination containing them substances and their use in medicine. 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 ...

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): C07D213/74A61P7/02
CPCC07D213/74
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