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

Fenbendazole analogue as well as preparation method and application thereof

A technology of fenbendazole and analogues, applied in the field of fenbendazole analogues and its preparation, to achieve the effects of inhibiting colony formation, inhibiting migration and invasion, inducing apoptosis and cell cycle arrest

Pending Publication Date: 2022-07-01
ZHEJIANG UNIV +1
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, studies at home and abroad have shown that fenbendazole has shown good research value in anti-tumor, and can effectively inhibit the proliferation and metastasis of lung cancer cells, especially K-RAS mutant lung cancer cells, but its effect in other cancer types The activity and mechanism of action have yet to be explored to supplement

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
  • Fenbendazole analogue as well as preparation method and application thereof
  • Fenbendazole analogue as well as preparation method and application thereof
  • Fenbendazole analogue as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1 (preparation of compound 3)

[0050]

[0051] Compound 3a (3.0 g, 12.2 mmol) was added to a mixed solution of EtOH (80.0 mL) / THF (30 mL) at 25°C, followed by Pd / C (3.0 g). Put the reaction mixture in H 2 The mixture was stirred at 25°C for 3h. The reaction mixture was then filtered and vacuum filtered to give 3b (2.5 g, 96.1%) as a black oil.

[0052] To a solution of 3b (2.5 g, 11.6 mmol) in DMF (30.0 mL) at 25 °C was added 3c (3.2 g, 13.9 mmol) and 4-methyl-morpholine (3.8 mL, 34.8 mmol). The reaction mixture was heated under nitrogen (N 2 ) at 25°C for 5 min, then EDCI.HCl (2.9 g, 15.1 mmol) and HOBt (2.0 g, 15.1 mmol) were added. Put the reaction mixture in N 2 Stir under protection at 25°C for 3h. mixture with H 2 Diluted with 0 (50 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with brine (100 mL) and concentrated. The crude product was purified by silica gel chromatography (EA:PE=1:2) to give 3d and 3e (4.8 g, 97...

Embodiment 2

[0056] Example 2 (preparation of compound 4)

[0057]

[0058] To a solution of compound 4a (5.0 g, 18.3 mmol) and MsCl (5.5 g, 27.5 mmol) in THF (300 mL) at 0 °C was added TEA (13 mL, 91.5 mmol). The reaction mixture was stirred at 70 °C for 16 h. The organic phase was dried and concentrated in vacuo and the residue was purified by column chromatography (eluting with PE in EA 0-90% to give 4d (5.1 g, yield: 19%) 4e (3.2 g, yield: 19%) .

[0059] To a solution of 4c (23.0 g, 117.3 mmol) in DMF (400 mL) was added NaH (7.0 g, 176.0 mmol) at 0 °C, and the reaction solution was stirred at 25 °C for 1 h. 4b (35.0 g, 125.4 mmol) was added dropwise to the mixture at 0°C. The reaction solution was stirred at 25 °C for 16 h, poured into ice water (1000 mL), the organic phase was dried, concentrated in vacuo, and the residue was purified by column chromatography (eluted with PE in EA 0-90% to give 4d (5.1 g, Yield: 19%) 4e (3.2 g, Yield: 19%).

[0060] 4d (3.2g, 8.41mmol), 4f (1...

Embodiment 3

[0062] Example 3 (preparation of compound 5)

[0063]

[0064] 4e (3.2g, 8.41mmol), Pd(dppf)Cl 2 (616.0 mg, 0.84 mmol), Xant-phos (486.4 mg, 0.84 mmol), t-BuOK (1.9 g, 16.82 mmol) and 4f (2.2 mmol, 16.82 mmol) in dioxane (30 mL) at 100 °C argon Stir under gas protection for 16h. The mixture was filtered and washed with ethyl acetate (50 mL). The filtrate was concentrated in vacuo and purified by silica gel chromatography (PE:ethyl acetate=5:1) to give 5a (2.9 g, yield: 85%) as a yellow solid.

[0065] Compound 5a (2.9 g, 7.08 mmol) was combined with a solution of HCl-EtOAc (3.0 M, 30 mL). Stir at 10°C for 3h. The resulting reaction mixture was concentrated in vacuo to give 5b (2.7 g, yield: >99%).

[0066] To hydrochloride-5b (2.79 g, 8.07 mmol) in THF / H 2 Add K to O (20mL / 5mL) solution 3PO4 (8.57 g, 40.35 mmol). The mixture was stirred at 10 °C for 5 min. 5 mL of acryloyl chloride in THF (803.37 mg, 8.88 mmol) was added slowly. The reaction mixture was stirred at...

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 provides a fenbendazole analogue as well as a preparation method and application thereof. The preparation method specifically comprises the following steps: 1-{4-[5-(thiophenyl)-1H-1, 3-benzimidazole-2-yl] piperidine-1-yl} propan-2-ene-1-one, 4-[4-[5-(thiophenyl)-1H-1, 3-benzimidazole-2-yl] piperidine-1-yl]-1 1-[(3R)-3-[5-(thiophenyl)-1H-indazolyl-1-yl] piperidine-1-yl] prop-2-en-1-one is used as a raw material, and the structural formula is shown in the description. The preparation method comprises the following steps: preparing 1-[(3R)-3-[5-(thiophenyl)-2H-indazolyl-2-yl] piperidine-1-yl] prop-2-en-1-one; the structural formula of [5-(thiophenyl)-1H-benzimidazole-2-yl] acrylamide is shown in the description. According to the invention, a mother nucleus of fenbendazole is modified by different substituent groups to synthesize the Nifenbendazole structural analogue. The fenbendazole and the analogue can inhibit HeLa cell proliferation in vitro, improve the concentration of active oxygen in HeLa cells and further activate a downstream apoptosis pathway, and can be applied to preparation of anti-cervical cancer drugs.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a fenbendazole analog and a preparation method and application. Background technique [0002] Cancer is a major public health problem in the world, and its morbidity and mortality are generally increasing year by year. The high morbidity and mortality of malignant tumors make the research on tumorigenesis mechanism and influencing factors, and the development of anticancer drugs become a hot topic nowadays. [0003] In the process of exploring and treating cancer, in addition to pinning their hopes on the development of new anti-cancer drugs, researchers have gradually turned their attention to non-anti-tumor drugs. This opens a new window into the treatment of cancer, making it an excellent alternative strategy to the classic anticancer drug discovery and development methods. Among them, antiparasitic drugs have attracted a lot of attention, especially benzimidazole anti...

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): C07D401/04C07D235/30A61P35/00A61K31/454A61K31/4184
CPCC07D401/04C07D235/30A61P35/00Y02P20/55
Inventor 余露山彭一曾苏
Owner ZHEJIANG UNIV
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