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

Disubstituted tetrazole acetophenone compound and preparation method and use thereof

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

Inactive Publication Date: 2014-10-01
XUZHOU FENGRUN BIOLOGICAL ORGANIC FERTILIZER TECH DEV CO LTD
View PDF3 Cites 4 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
  • Disubstituted tetrazole acetophenone compound and preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] .

[0030] Reaction raw materials: self-made, conventional method.

[0031] 2.20 g (10 mmol) compound II-1 , 3.70 g (10 mmol) compound III-1 and 4.15 g (30 mmol) of solid potassium carbonate were stirred overnight in 20 mL of acetonitrile, and then heated to reflux for 3 hours.

[0032] The reaction mixture was cooled slightly and poured into 200 mL ice water, stirred, adjusted to pH = 4 with concentrated hydrochloric acid, extracted with 50 mL × 3 dichloromethane, combined organic phases, washed with brine, dried over anhydrous sodium sulfate, and dried on a rotary evaporator The solvent was evaporated, and the obtained residue was purified by column chromatography to obtain pure I-1 , white solid, MS, m / z = 518 ([M+Na] + ).

Embodiment 2-4

[0034] According to the method of Example 1, synthesized with general formula I of the following compounds:

[0035] .

Embodiment 5

[0036] Example 5 In vitro platelet aggregation inhibition test

[0037] Pharmacological testing of substances 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, at 1500 g Platelet-rich plasma (PRP) was separated by centrifugation for 20 minutes and treated with 1 μL PGE1 solution (500 μg / mL in ethanol) / mL PRP. 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 NaHCO3, 0.39 mM NaH2PO4, 10 mM HEPES, 0.35% BSA, 5.5 mM Glucose, pH = 7.4) and adjusted to a platelet count of 3 × 105 / μL ...

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, in particular to a disubstituted PAR-1 (Protease Activated Acceptor-1) agonist containing a tetrazole acetophenone structure, a preparation method thereof, a medicine composition containing the PAR-1 agonist and application of the PAR-1 agonist to preparation of medicines for treating thrombotic diseases. The formula (I) and the definition of R group are 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 class of disubstituted tetrazoleacetophenone-containing PAR-1 antagonists that have a therapeutic effect on thrombotic diseases, a preparation method thereof, and a pharmaceutical composition containing them. 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 thrombus formation, and can be used ...

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): C07D257/04A61K31/5377A61P7/02
CPCC07D257/04
Inventor 张远强
Owner XUZHOU FENGRUN BIOLOGICAL ORGANIC FERTILIZER TECH DEV 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