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

Cholic acid derivative as well as preparation method and application thereof

A technology for cholic acids and derivatives is applied in the field of cholic acid derivatives and their preparation, and achieves broad application prospects, inhibits liver cell damage, and inhibits liver cell apoptosis.

Active Publication Date: 2020-02-18
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still few types of organic substances that can inhibit the apoptosis of hepatocytes

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
  • Cholic acid derivative as well as preparation method and application thereof
  • Cholic acid derivative as well as preparation method and application thereof
  • Cholic acid derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0064] The present invention provides the preparation method of cholic acid derivative described in above-mentioned scheme, comprises the following steps:

[0065] When R 1 with R 1 ’ Same, R 2 with R 2 ’ Same, R 3 with R 3 ’ same, when Y is the following group,

[0066]

[0067]

[0068] The preparation method of described cholic acid derivatives comprises the following steps:

[0069] (1) under the action of a condensing agent, the compound of the structure shown in formula A is reacted with N-hydroxysuccinimide to obtain an intermediate having the structure shown in formula 1-1;

[0070]

[0071] (2) The intermediate having the structure shown in formula 1-1, the compound Y1 and the solvent are mixed and reacted to obtain cholic acid derivatives; the compound Y1 has one of the following structures:

[0072]

[0073] Concrete synthetic route is as shown in formula one:

[0074]

[0075] In the present invention, under the action of a condensing agent, ...

Embodiment 1

[0127](4R,4'R)-N,N'-(ethane-1,2-diyl)bis(4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3 , 7-dihydroxyl-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl) pentamide) synthesis; denoted as compound 1a, the steps are as follows:

[0128] Add ursodeoxycholic acid (10g, 25.47mmol), EDCI (4.40g, 38mmol), N-hydroxysuccinimide (3.5g, 30.5mmol) and anhydrous DMF (50mL) to the flask successively, at 35°C , Stir the reaction under the protection of argon for 12h. Water (120 mL) was added to the reaction and extracted with ethyl acetate (3 x 50 mL). The combined organic phases were washed with saturated NaHCO 3 solution (3×50mL) and washed with Na 2 SO 4 dry. The extract was concentrated under reduced pressure to obtain the product (1-1) (8.08 g, 64%) as a white powder. 1 HNMR (600MHz, CD 3 OD-d 4 )δ3.55-3.46(m,2H),2.84(s,4H),2.72-2.64(m,1H),2.62-2.52(m,1H),2.07(dt,J=12.8,3.4Hz,1H) ,1.98-1.79(m,4H),1.68-1.18(m,16H),1.13(q,J=9.5Hz,1H),1.09-1.04(m,1H),1.03-0.98(m,6H),0.76 –0.7...

Embodiment 2

[0132] Ethane-1,2-diyl(4R,4'R)-bis(4-(((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy- 10,13-hexadecyldimethyl-1H-cyclopenta[a]phenanthrenyl-17-yl) pentanoate) synthesis, denoted as compound 2a; The steps are as follows:

[0133] Add ursodeoxycholic acid (3g, 7.64mmol), 1,4-dioxane (15mL), 3,4-dihydro-2H-pyran (1.93g, 22.9mmol) and p-toluenesulfonate to the flask successively Acid hydrate (0.29g, 1.53mmol), stirred at room temperature for 3h. Water (50 mL) was added to the reaction and extracted with ethyl acetate (3 x 30 mL). The combined extracts were washed with anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure, and purify by silica gel column chromatography. Elution with 1:10 to 1:5 ethyl acetate-n-hexane gave (2-1) (2.8 g, 65%) as a white powder. 1 H NMR (600MHz, Chloroform-d) δ3.94–3.82(m,3H),3.64–3.32(m,3H),2.43–2.34(m,1H),2.29–2.20(m,1H),2.01–0.96 (m,22H),0.95–0.91(m,6H),0.69–0.63(m,3H).

[0134] Put (2-1) (0.5g, 0.9mmol), HOBT (0.15g, 1.08mmol), EDCI ...

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 technical field of medicine synthesis, and provides a cholic acid derivative as well as a preparation method and application thereof. The cholic acid derivative provided by the invention has a remarkable effect of inhibiting hepatocyte apoptosis, can effectively inhibit hepatocyte damage induced by glycochenodeoxycholic acid, and the inhibition rate of part of the derivative is superior to that of a positive control tauroursodeoxycholic acid; the cholic acid derivative provided by the invention provides a reference for research and development of liver protection drugs, and has a wide application prospect in preparation of the liver protection drugs.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical synthesis, in particular to a bile acid derivative and its preparation method and application. Background technique [0002] Liver injury is a common pathological state in clinical practice. The causes of liver injury include hepatitis virus, alcohol, drug abuse, free fatty acid metabolism syndrome, immune-mediated inflammatory processes affecting the liver, and genetic diseases. Apoptosis of hepatocytes is a characteristic of liver injury, and at the same time, hepatocytes have a strong regenerative function through cell proliferation. For example, 70% of livers after hepatectomy regenerate to their original mass within about 1 week. However, when cell loss exceeds a certain threshold, liver regeneration is insufficient to counteract hepatocyte apoptosis, and functional hepatocytes are replaced by fibrotic scars, compromising liver function and ultimately leading to chronic liver disease....

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 Applications(China)
IPC IPC(8): C07J9/00A61P1/16
CPCA61P1/16C07J9/00C07J9/005
Inventor 王玉成王菊仙何红伟牛伟萍牛伟晓张国宁朱梅王明华
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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