Bi[indole-3-yl-acetylamino acid] connected by ethyl, preparation method, antithrombotic function, and applications thereof

An acetyl amino acid, anti-thrombotic technology, applied in the field of anti-thrombotic activity, application of anti-thrombotic agents, bis[indol-3-yl)-acetyl amino acid], to achieve a wide range of pharmacological activities and good anti-thrombotic activity

Inactive Publication Date: 2013-12-18
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
View PDF5 Cites 19 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Antithrombotic drugs already o

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
  • Bi[indole-3-yl-acetylamino acid] connected by ethyl, preparation method, antithrombotic function, and applications thereof
  • Bi[indole-3-yl-acetylamino acid] connected by ethyl, preparation method, antithrombotic function, and applications thereof
  • Bi[indole-3-yl-acetylamino acid] connected by ethyl, preparation method, antithrombotic function, and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 Preparation of {2-[1-(3-methoxycarbonylmethyl-1H-indol-2-yl)-ethyl]-1H-indol-3-yl}-acetic acid methyl ester (3)

[0024] Dissolve 1.0g (5.7mmol) indole acetic acid in 15ml of methanol solution at room temperature, stir until dissolved, slowly add 2.5ml of SOCl dropwise at 0°C 2 , reacted at room temperature for 24h, TLC detected that the raw material point basically disappeared (petroleum ether: acetone 3:1). 2ml of acetaldehyde (40%) was added to the reaction mixture, and the reaction was stirred at room temperature for 24h. The reaction mixture was concentrated to dryness under reduced pressure, and the residue was first purified by column chromatography (petroleum ether: acetone 9:1) and then recrystallized to obtain 320 mg (28%) of the title compound as colorless crystals. [α] 25 D =-20.4 (c=1, CH 3 OH). 1 HNMR (DMSO-d 6 )δ / ppm=10.84(s, 2H), 7.40(d, J=7.8Hz, 2H), 7.36(d, J=8.1Hz, 2H), 7.06(t, J=7.2Hz, 2H), 6.97( t, J=7.2Hz, 2H), 4.78(q, J=7.5Hz, 1H...

Embodiment 2

[0025] Example 2 Preparation of {2-[1-(3-methoxycarbonylmethyl-1H-indol-2-yl)-ethyl]-1H-indol-3-yl}-acetic acid (4)

[0026] Take 100 mg (0.26 mmol) of compound 3 and dissolve it in 10 ml of methanol, adjust the pH value to 13-14 with 4N NaOH aqueous solution, stir in ice bath for 8 h, TLC detects that the raw material point disappears (petroleum ether: acetone 3: 1), and saturate KHSO 4 Adjust the pH of the aqueous phase to neutral, concentrate under reduced pressure, dissolve the residue with a small amount of distilled water, and wash the aqueous phase with ethyl acetate three times. The aqueous phase was adjusted to pH 2 with saturated KHSO4, and extracted three times with ethyl acetate. The ethyl acetate layer was washed 3 times with saturated NaCl solution, anhydrous NaCl 2 SO 4 Dry, filter, and concentrate the filtrate under reduced pressure to afford 93 mg (93%) of the title compound as a pale yellow powder. [α] 25 D =96.9 (c=1, CH 3 OH). 1 HNMR (DMSO-d 6 )δ / pp...

Embodiment 3

[0027] Example 3 Preparation of {2-[1-(3-methoxycarbonylmethyl-1H-indol-2-yl)-ethyl]-1H-indol-3-yl}-acetyl-L-Ala- OCH 3 (5a)

[0028] Take 752mg (2mmol) of compound 4 in a 100ml eggplant bottle, dissolve it with a small amount of anhydrous tetrahydrofuran (THF), add 540mg (4mmol) of 1-hydroxybenzotriazole (HOBt) under stirring in an ice bath, add 989mg (4.8mmol) ) dicyclohexylcarbodiimide (DCC), activated for 30min. Take 670mg (2mmol) HCl AlaOCH 3 In a 25ml small Erlenmeyer flask, suspend with anhydrous tetrahydrofuran (THF), adjust the pH to neutral with N-methylmorpholine (NMM), then add the suspension dropwise to the activated reaction solution, and finally use NMM Adjust the pH value of the reaction solution to 8, react overnight at room temperature, monitor by TLC until the raw material spots disappear, filter to remove dicyclohexyl urea (DCU), concentrate the filtrate to dryness under reduced pressure and dissolve it with ethyl acetate, then filter again to remove DCU...

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 discloses 14 novel compounds, which are represented by the formula I, of bi[indole-3-yl)-acetylamino acid] connected by ethyl, wherein the AA is selected from L-Ala, Gly, L-Phe, L-Trp, L-Tyr, L-Ile, L-Leu, L-Glu, L-Asp, L-Met, L-Ser, L-Thr, L-Pro, and L-Val residuals, discloses a preparation method of the compounds, and also discloses antithrombotic activity of the compounds, and applications of the compounds as a antithrombotic agent.

Description

technical field [0001] The present invention relates to 14 novel ethyl-linked bis[indol-3-yl)-acetylamino acids] represented by general formula I (AA in the formula is selected from L-Ala, Gly, L-Phe, L-Trp, L- Tyr, L-Ile, L-Leu, L-Glu, L-Asp, L-Met, L-Ser, L-Thr, L-Pro and L-Val residues), their preparation methods, and their antithrombotic activity and its use as an antithrombotic agent. The invention belongs to the field of biomedicine. [0002] Background technique [0003] Cardiovascular and cerebrovascular disease is a high-incidence disease that has seriously endangered public health, especially the health of the elderly. At present, the death rate caused by cardiovascular and cerebrovascular diseases in the world has ranked first in the death rate of other diseases. The formation of thrombus can lead to various diseases, such as pulmonary thromboembolism, atherosclerosis, coronary heart disease, cerebrovascular disease, deep vein embolism after surgery or traum...

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): C07D209/18C07D209/20C07D403/14A61P7/02
Inventor 赵明彭师奇吴建辉王玉记元华龙
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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