PAR (Protease Activated Receptor)-1 antagonist as well as preparation method and application of PAR-1 antagonist

One aspect, the technology of oral preparations, applied in the field of pharmaceutical compositions containing it, can solve problems such as high bleeding risk

Inactive Publication Date: 2014-10-08
王佳
View PDF4 Cites 13 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of these drugs

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
  • PAR (Protease Activated Receptor)-1 antagonist as well as preparation method and application of PAR-1 antagonist
  • PAR (Protease Activated Receptor)-1 antagonist as well as preparation method and application of PAR-1 antagonist
  • PAR (Protease Activated Receptor)-1 antagonist as well as preparation method and application of PAR-1 antagonist

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025]

[0026] Reaction raw materials: self-made, conventional method.

[0027] 1.46 g (10 mmol) compound II , 3.70 g (10 mmol) compound III 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.

[0028] 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 , white solid, MS, m / z = 458 ([M+Na] + ).

Embodiment 2

[0029] Example 2 In vitro platelet aggregation inhibition test

[0030] 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, 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 o...

Embodiment 3

[0034] Dosage / tablet

[0035] Compound I 5mg

[0036] Microcrystalline Cellulose 80 mg

[0037] Pregelatinized starch 70 mg

[0038] Polyvinylpyrrolidone 6 mg

[0039] Carboxymethyl starch sodium salt 5 mg

[0040] Magnesium stearate 2 mg

[0041]Talc 2 mg.

[0042] Sieve the active ingredient, pregelatinized starch and microcrystalline cellulose, mix well, add polyvinylpyrrolidone solution, mix, make soft material, sieve, make wet granules, dry at 50-60°C, carboxymethyl Sodium starch salt, magnesium stearate and talc powder are pre-screened and then added to the above granules for tableting.

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 drugs and particularly relates to a PAR (Protease Activated Receptor)-1 antagonist with a brand new structure as the specification, a preparation method of the PAR-1 antagonist, a pharmaceutical composition containing the PAR-1 antagonist and an application of the PAR-1 antagonist to preparation of drugs 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 with a new structure and a preparation method thereof, as well as a pharmaceutical composition containing it, which has a therapeutic effect on 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 thrombus formation, and can be used to treat acute coronary syn...

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): C07D257/04A61K31/5377A61P7/02
CPCC07D257/04
Inventor 张远强
Owner 王佳
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap