RGD tetrapeptide modified s,r-heptacyclic aldehyde, its synthesis, activity and application

A reaction, 4-b technology, application in the preparation of P-selectin antagonists, application in the preparation of GPIIb/IIIa antagonists, inhibition of in vivo P-selectin expression activity, anti-arterial thrombosis activity, S, R-heptacyclic aldehyde-Arg-Gly-Asp-AA field, can solve problems such as reduction

Inactive Publication Date: 2021-06-08
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effective dose of β-carboline, such as 3S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid antithrombotic effective dose is as high as 5 μmol / kg, which still needs to be reduced

Method used

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  • RGD tetrapeptide modified s,r-heptacyclic aldehyde, its synthesis, activity and application
  • RGD tetrapeptide modified s,r-heptacyclic aldehyde, its synthesis, activity and application
  • RGD tetrapeptide modified s,r-heptacyclic aldehyde, its synthesis, activity and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026]Example 1 Preparation of 1-(2,2-dimethoxyethyl)-2,3,4,9-tetrahydro-β-carboline-3-carboxylic acid benzyl ester (1)

[0027] Under ice-bath conditions, add 5 mL of 1,1,3,3-tetramethoxypropane and 5 mL of trifluoroacetic acid to 150 mL of dichloromethane in sequence, and activate in an ice-water bath for 40 min. Then 5.00 g (17.00 mmol) benzyl L-tryptophan was added. The solution was reddish brown. The reaction mixture was first stirred under ice bath for 1 h, and then stirred at room temperature for 12 h. The reaction solution was extracted and washed 6 times with saturated aqueous sodium bicarbonate solution, and a large number of bubbles would be generated. Extract and wash with saturated sodium chloride aqueous solution 3 times. The dichloromethane layer was collected and dried by adding anhydrous sodium sulfate for 2 hours. After filtration under normal pressure, the filtrate was concentrated under reduced pressure and then purified by silica gel column chromatogra...

Embodiment 2

[0028] Example 2 Preparation of 1-(2,2-dimethoxyethyl)-2,3,4,9-tetrahydro-β-carboline-3-carboxylic acid (2)

[0029] Add 540 mg of Pd / C to 5.39 g (13.68 mmol) of compound 1 and 100 mL of methanol solution, feed H 2 , Stir the reaction at room temperature for 4h. Pd / C was filtered off, and the filtrate was concentrated under reduced pressure to obtain 3.34 g (11.00 mmol) of the title compound as a yellow oil, with a yield of 80%. ESI-MS(m / e): 303[M-H] - .

Embodiment 3

[0030] Example 3 Preparation of (2S,5S)-tetrahydropyrazine[1,2:1,6]bis{(1S,1R)-[1-dimethoxyethyl-2-yl]-2,3, 4,9-tetrahydro-1H-pyridino[3,4-b]indole}-1,4-dione (3)

[0031] Suspend 3.34g (11.00mmol) of compound 2 in 60mL of N,N-dimethylformamide, add 1.49g (11.00mmol) of N-hydroxybenzotriazole and 2.72g of (13.20 mmol) dicyclohexylcarbodiimide, and then adjust the pH of the reaction solution to 8-9 with N-methylmorpholine. Reaction at room temperature for 8 hours. The reaction solution was filtered under reduced pressure, and the filtrate was concentrated under reduced pressure. Dissolve it with 100 mL of ethyl acetate, and a white solid is precipitated or insoluble. Filter under reduced pressure and collect the filtrate. The obtained ethyl acetate solution was washed successively with saturated aqueous sodium bicarbonate solution 3 times, saturated aqueous sodium chloride solution 3 times, 5% potassium bisulfate aqueous solution 3 times, saturated sodium chloride aqueous s...

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Abstract

The present invention discloses a kind of S,R-heptacyclic aldehyde-Arg-Gly-Asp-AA, discloses their preparation method, discloses their anti-venous thrombosis activity, discloses their anti-arterial thrombosis activity, discloses their Inhibiting the activity of GPIIb / IIIa expression in vivo, disclosing their activity of inhibiting the expression of P-selectin in vivo, disclosing the dose-effect relationship of S,R-heptacyclic aldehyde-Arg-Gly-Asp-Ser anti-arterial and venous thrombosis activity. Therefore, the present invention discloses their application in the preparation of anti-arterial thrombosis drugs, the application in the preparation of anti-venous thrombosis drugs, the application in the preparation of GPIIb / IIIa antagonists and the application in the preparation of P-selectin antagonists.

Description

technical field [0001] The present invention relates to S,R-heptacyclic aldehyde-Arg-Gly-Asp-AA, to their preparation process, to their antivenous thrombosis activity, to their antiarterial thrombosis activity, to their inhibition of glycoprotein IIb / IIIa in vivo (IIb / IIIa) expressed activity related to their activity to inhibit P-selectin expression in vivo. Therefore, the present invention relates to their application in the preparation of anti-arterial thrombosis drugs, their application in the preparation of anti-venous thrombosis drugs, their application in the preparation of GPIIb / IIIa antagonists, and their applications in the preparation of P-selectin antagonists. The invention belongs to the field of biomedicine. Background technique [0002] Thrombosis is a common pathology of ischemic heart disease, ischemic stroke and venous thrombosis. Globally, ischemic heart disease and ischemic stroke account for a quarter of all deaths from disease. Venous thrombosis is t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/11C07K1/02G01N33/68A61K38/07A61P7/02
CPCA61K38/00A61P7/02C07K5/1019C07K19/00G01N33/68G01N2410/00
Inventor 赵明蒋雪云桂琳彭师奇薛双悦
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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