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1,1-Dimethyl-β-carbolinecarboxylic acid modified RGD peptide, its synthesis, antithrombotic effect and application

A carboline carboxylic acid, dimethyl technology, applied in the field of RGD peptide, can solve the problem of no antithrombotic compound

Inactive Publication Date: 2016-03-30
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • 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

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  • 1,1-Dimethyl-β-carbolinecarboxylic acid modified RGD peptide, its synthesis, antithrombotic effect and application
  • 1,1-Dimethyl-β-carbolinecarboxylic acid modified RGD peptide, its synthesis, antithrombotic effect and application
  • 1,1-Dimethyl-β-carbolinecarboxylic acid modified RGD peptide, its synthesis, antithrombotic effect and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Embodiment 1 prepares Boc-Ala

[0063]Under ice-bath stirring, 5g (56.18mmol) Ala was dissolved in 160ml of distilled water, and then the pH value was adjusted to 8 with 2N NaOH solution, and 15.92g (73.0mmol) (Boc) was dissolved with 160ml dioxane 2 O is dissolved, then added to the reaction flask, under ice-bath stirring, 2N NaOH solution is added dropwise to adjust the pH to 9, and water or dioxane is added, and the volume ratio of water and dioxane in the reaction solution is 1:1. The pH value of the reaction solution was adjusted to 9, and CO was pumped from time to time. 2 , to promote the reaction to the right, and after 48 hours of reaction, the raw materials disappeared. Reaction compound with saturated KHSO 4 Adjust the pH of the reaction solution to 7, concentrate under reduced pressure to remove dioxane, and then wash the residue with saturated KHSO 4 Adjust the pH of the reaction solution to 2, extract with ethyl acetate, a small amount of multiple times...

Embodiment 2

[0064] Embodiment 2 prepares Tos·Gly-OBzl

[0065] Weigh 7.5g (100mmol) of Gly, add 18.06g (105mmol) of p-toluenesulfonic acid, 60ml of benzyl alcohol and 30ml of cyclohexane, and place the mixture in an oil bath that has been heated to 90°C in advance. Install the water separator and condenser, start the reaction, TLC (dichloromethane:methanol 5:1) after 24h shows that the raw material disappears, the oil bath is lowered to room temperature, add a large amount of ether, stir, and filter after the precipitation is complete to obtain 27.5 g (81%) of the title compound as a colorless solid. Mp132-133℃.ESI-MS(m / e)338[M+H] + .

Embodiment 3

[0066] Embodiment 3 prepares Boc-Ala-Gly-OBzl

[0067] Weigh 3.36g (17.7mmol) Boc-Ala and dissolve it with 80ml of anhydrous THF, add 2.40g (17.7mmol) of HOBt in an ice bath, and add 3.67g (17.7mmol) of DCC and anhydrous THF after 10min The solution, stirred for 30min, is called solution I. 5g (14.8mmol) of Tos·Gly-OBzl was dissolved in anhydrous THF, N-methylmorpholine was added dropwise to adjust the pH to 9, and stirred for 30min, which was called solution II. Mix solution I and solution II, react at room temperature for 8 hours, monitor the disappearance of the reaction raw materials on a TLC board, filter the reaction solution after stopping the reaction, and concentrate the filtrate to dryness under reduced pressure. Add petroleum ether to the viscous substance obtained, continue to grind and wash, and then let it stand and pour, the remaining substance is dissolved with ethyl acetate, and saturated NaHCO 3 Alkaline wash, then saturated KHSO 4 After acid washing and f...

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Abstract

The invention discloses 1,1-dimethyl-beta-carboline carboxylic acid-modified RGD peptides shown in the general formula I. In the general formula I, when AA1 represents Ala, AA2 represents Val, Phe or Ser, and when AA1 represents Arg, AA2 represents Val, Phe or Ser. The invention also discloses a preparation method, an anti-thrombus effect and a use of the 1,1-dimethyl-beta-carboline carboxylic acid-modified RGD peptides as anti-thrombus agents.

Description

technical field [0001] The present invention relates to 1,1-dimethyl-beta-carboline carboxylic acid modified RGD peptide represented by general formula I (AA in the formula 1 When Ala, AA 2 For Val;AA 1 When Ala, AA 2 is Phe; AA 1 When Ala, AA 2 Ser; AA 1 When it is Arg, AA 2 For Val;AA 1 When it is Arg, AA 2 is Phe; AA 1 When it is Arg, AA 2 Ser), relate to their preparation method, also relate to their antithrombotic activity and its application as antithrombotic agent. The invention belongs to the field of biomedicine. [0002] Background technique [0003] Globally, thrombotic disease is the leading cause of morbidity and mortality. There are two types of thrombi in patients with thrombosis, one is a thrombus formed by cross-linking platelets with white blood cells through fibrinogen, and the other is a thrombus formed by cross-linking platelets through fibrinogen and platelets. [0004] P-selectin exists in two forms: soluble P-selectin and insoluble P-s...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/103C07K5/107C07K5/11C07K1/06A61K38/07A61P7/02
Inventor 彭师奇赵明吴建辉王玉记高俊华
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES