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

rgd peptide-modified carboline hexahydropyrazine-1,4-dione, its preparation method, antithrombotic effect and application

A technology of hexahydropyrazine and antithrombotic drugs, which is applied in the field of biomedicine and can solve the problems of no antithrombotic compounds

Inactive Publication Date: 2015-09-09
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although inhibition of insoluble P-selectin expression and cleavage to soluble P-selectin is considered an important target for the design of antithrombotic drugs, few antithrombotic compounds have been linked to this target

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
  • rgd peptide-modified carboline hexahydropyrazine-1,4-dione, its preparation method, antithrombotic effect and application
  • rgd peptide-modified carboline hexahydropyrazine-1,4-dione, its preparation method, antithrombotic effect and application
  • rgd peptide-modified carboline hexahydropyrazine-1,4-dione, its preparation method, antithrombotic effect and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 Preparation of (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (1)

[0027] Put 400ml water in a 500ml eggplant bottle and slowly add 0.2ml concentrated sulfuric acid. Add 5.0 g (24.5 mmol) of L-tryptophan to the obtained dilute sulfuric acid aqueous solution, and ultrasonically shake until the L-tryptophan is completely dissolved. 7.5 ml of 40% formaldehyde solution was added to the solution, and the reaction mixture was stirred at room temperature for 6 hours. TLC monitored the disappearance of L-tryptophan, and the reaction was terminated. Concentrated ammonia water was slowly added dropwise to the reaction solution, the pH of the reaction mixture was adjusted to 6, and it was allowed to stand for 0.5 hour. The precipitate was filtered under reduced pressure, washed with water, the filtered colorless solid was spread flat in a petri dish, and air dried to obtain 5.14 g (97%) of the title compound. ESI-MS(m / e): 217[M+H] + .

Embodiment 2

[0028] Example 2 Preparation of (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester (2)

[0029] Add 50ml methanol to a 100ml eggplant bottle, cool to below 0℃ with an ice-salt bath, add 6ml (87mmol) SOCl dropwise with stirring 2 After 10 minutes of dropping, add 5.0 g (23.1 mmol) (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, remove the ice bath, and stir overnight at room temperature. The reaction is stopped after TLC monitors the disappearance of the raw materials, and the water pump depressurizes the methanol and excess SOCl 2 , The residue is dissolved in methanol again, the circulating water vacuum pump is drained, and this is repeated three times (10ml×3), the residue is added with ether, and the circulating water vacuum pump is drained, and repeated three times (10ml×3). Add 20ml water and 20ml ethyl acetate to the residue, and add saturated NaHCO 3 The pH of the solution was adjusted to 7-8, the layers were separated, the ethyl acetate layer was col...

Embodiment 3

[0030] Example 3 Preparation of (3S)-N-[Boc-(OBzl)aspartyl]-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester (3)

[0031] Dissolve 1.61g (5mmol) Boc-Asp (OBzl) in 50ml of anhydrous dichloromethane, add 742mg (6mmol) HOBt and 1.42g (6mmol) DCC under ice bath. After stirring for 5-10 minutes, the reaction solution appears turbid, add 1.15g (5mmol) (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester, remove the ice bath after 30 minutes. The reaction was carried out at room temperature for 12 hours, TLC showed that the starting material point disappeared, the reaction was stopped, DCU was filtered off, the filtrate was concentrated to dryness under reduced pressure at 30°C, and the residue was dissolved in ethyl acetate. Then washed with saturated sodium bicarbonate aqueous solution, saturated sodium chloride aqueous solution, 5% potassium hydrogen sulfate aqueous solution, saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueou...

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

PropertyMeasurementUnit
particle diameteraaaaaaaaaa
Login to View More

Abstract

The invention discloses RGD peptide-modified carbolino-hexahydropyrazine-1,4-diketones, which are three novel conjugates of carbolino-hexahydropyrazine-1,4-diketone and RGD tetrapeptide and are shown in the general formula I. In the general formula I, R represents Arg-Gly-Asp-Val, Arg-Gly-Asp-Phe or Arg-Gly-Asp-Ser. The invention also discloses heterocyclic nucleuses of the novel conjugates, wherein R represents OH. The invention also discloses a preparation method and in-vitro anti-platelet aggregation effects of the novel conjugates, and also discloses an antithrombotic use of the novel conjugates in a rat thrombus formation model. A result shows that the three novel conjugates of carbolino-hexahydropyrazine-1,4-diketone and RGD tetrapeptide (wherein R represents Arg-Gly-Asp-Val, Arg-Gly-Asp-Phe or Arg-Gly-Asp-Ser) and their heterocyclic nucleuses (wherein R represents OH) have good antithrombotic activity and clear application prospects in antithrombotic agent preparation.

Description

Technical field [0001] The present invention relates to general formula 1 (R represents Arg-Gly-Asp-Val, Arg-Gly-Asp-Phe and Arg-Gly-Asp-Ser) carboline hexahydropyrazine-1,4-dione and The three novel conjugates of RGD tetrapeptides and their heterocyclic nuclei (R stands for OH) relate to their preparation methods, their in vitro anti-platelet aggregation effects, and their effects on rat thrombosis models. Antithrombotic effect. The results showed that the formula 1 of the present invention (R represents Arg-Gly-Asp-Val, Arg-Gly-Asp-Phe and Arg-Gly-Asp-Ser) carboline hexahydropyrazine-1,4-di The three novel conjugates of ketone and RGD tetrapeptide and their heterocyclic nuclei (R represents OH) have good antithrombotic activity and have clear application prospects in the preparation of antithrombotic agents. The invention belongs to the field of biomedicine. [0002] Background technique [0003] Globally, the incidence and mortality of thrombotic diseases rank first. There...

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): C07K5/11C07K1/06C07D471/14A61K31/4985A61P7/02
Inventor 赵明彭师奇王玉记吴建辉韩爽
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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