Unlock instant, AI-driven research and patent intelligence for your innovation.

Morphinan compound as well as preparation method and application thereof

A compound and morphinan technology, which are applied in the field of morphinan compounds and their preparation, can solve the problems of elevated liver enzymes, insignificant fibrosis effect, and high price of nintedanib, and can inhibit cell fibrosis with good effect. , the effect of high safety

Pending Publication Date: 2022-04-29
广东克冠达医药科技有限公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, nintedanib is not only expensive, but also has side effects such as diarrhea, nausea and vomiting, abdominal pain, loss of appetite, weight loss, and elevated liver enzymes, and it is mainly aimed at idiopathic pulmonary fibrosis, and has no obvious effect on other types of fibrosis

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
  • Morphinan compound as well as preparation method and application thereof
  • Morphinan compound as well as preparation method and application thereof
  • Morphinan compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] The preparation of embodiment 1 morphinan compound A

[0055] The specific reaction steps for the preparation of the morphinan compound A are as follows:

[0056]

[0057]S1. Add dimethyl sulfide (12 mmol, 1.2 equivalents) and 2-bromo-4'-methylacetophenone (10 mmol, 1 equivalents) into 45 ml of acetone solution, stir at room temperature overnight; collect the precipitate by filtration, and use a small amount of Acetone washing; the resulting precipitate was dispersed with 30ml of dichloromethane, added sodium hydroxide (50mmol, 5 equivalents) aqueous solution (10ml), stirred at room temperature for 40 minutes, the organic layer was taken, the aqueous layer was extracted with dichloromethane, and the organic layers were combined. It was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to give dimethyl[2-(4-methylphenyl)-2-oxyethyl]inyl salt (yield: 83%).

[0058]

[0059] S2. Add iodobenzene acetate (6.52 mmol, 1.1 e...

Embodiment 2

[0062] Red solid, melting point 188-189℃, 1 H NMR (300MHz, CDCl 3 )δ7.87-7.84(d,J=8.0Hz,2H),7.36-7.34(d,J=8.0Hz,2H),6.87(s,1H),6.62(s,1H),5.27(s,1H ),4.31-4.25(d,J=16.1Hz,1H),3.92-3.91(d,J=2.8Hz,1H),3.39(s,3H),3.21(s,1H),2.66-2.39(m, 7H),2.02-1.87(m,3H)ppm; 13 C NMR (75MHz, CDCl 3 )δ 192.3, 175.4, 157.6, 157.2, 152.8, 149.8, 142.7, 141.3, 130.1, 128.0, 125.9, 121.2, 113.1, 109.8, 106.3, 100.2, 62.2, 55.0, 48.1, 467.6, 24, 4.2, 43.2 ppm; HRMS (ESI) calcd for [C 27 h 25 NO 5 +H] + 444.1805, found 444.1902. See the NMR spectrum Figure 1~2 . The preparation of embodiment 2 morphinans compound B

[0063] The specific reaction steps for the preparation of the morphinan compound B are as follows:

[0064]

[0065] S1. Add dimethyl sulfide (12mmol, 1.2 equivalents) and 2-bromo-4'-fluoroacetophenone (10mmol, 1 equivalents) into 45ml of acetone solution, stir at room temperature overnight; collect the precipitate by filtration, and use a small amount of acetone Washing; ...

experiment example 1

[0071] Toxicity test (MTT method) of experimental example 1 morphinan compound to fibrosis cell

[0072] NIH / 3T3 cells (purchased from the Chinese Academy of Sciences) were placed in DMEM medium containing 10% fetal bovine serum at 37°C, 5% CO 2 cultured in a humidified incubator. Add 100 μL of NIH / 3T3 cells at a concentration of 7000 / well to each well of a 96-well culture plate, at 37°C, 5% CO 2 Incubate for 24 hours; give different concentrations of the compound to be tested after attaching to the wall. After 24 hours of action, add 10 μl of MTT to continue incubation for 4 hours, discard the supernatant, add 150 μl of DMSO, and use a full-wavelength multifunctional microplate reader to detect the absorbance at 490 nm. The toxic effect of compounds on fibrotic cells was determined.

[0073] See results Figure 5-6 ,Depend on Figure 5 It can be seen that in the concentration range of 0.39-200 μM, compound A has no obvious toxic effect on fibrotic cell NIH / 3T3; after dilu...

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 belongs to the technical field of biological medicines, and particularly relates to a morphinan compound as well as a preparation method and application thereof. Experiments prove that the morphinan compound has no obvious toxicity to fibrotic cells, is high in safety, can achieve the effect of remarkably inhibiting cell fibrosis by inhibiting expression of alpha-sma, cologen1 and fibronectin, is better in safety and anti-fibrosis effect even compared with a positive control drug, has a remarkable progress, and has a good application prospect. The traditional Chinese medicine composition is very suitable for treating fibrosis diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to a morphinan compound and its preparation method and application. Background technique [0002] Fibrosis refers to the process in which normal organs or tissues are transformed into fibrotic tissues composed of fibroblasts and extracellular matrix containing collagen and fibronectin after being damaged beyond their own repair capacity. Generally, when an organ is slightly damaged, fibroblasts in the tissue will participate in the repair process, secrete extracellular matrix and promote wound contraction, and the damaged part will be quickly replaced by regenerated normal tissue. However, after an organ or tissue is severely damaged, fibroblasts will secrete excessive extracellular matrix, and the body's own regeneration ability cannot completely repair the damage, resulting in the final replacement of the damaged part by fibrotic tissue, which eventually damag...

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): C07D498/08A61K31/439A61P43/00A61P17/00A61P9/00A61P11/00A61P1/16A61P13/12
CPCC07D498/08A61P43/00A61P17/00A61P9/00A61P11/00A61P1/16A61P13/12Y02P20/55
Inventor 刘洪恩
Owner 广东克冠达医药科技有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com