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

Oxazole histone deacetylase inhibitor and preparation method thereof

A deacetylase and inhibitor technology, applied in the field of new drug compounds, can solve the problems of unclear curative effect of B-cell lymphoma, poor curative effect and low activity of solid tumors, and achieve strong inhibitory effect, good effect and low overcoming activity. Effect

Inactive Publication Date: 2021-03-16
WUYI UNIV
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the efficacy of HDAC inhibitors in the treatment of B-cell lymphoma is currently unclear.
[0005] In addition, HDAC inhibitors currently on the market generally have low activity and poor curative effect on solid tumors.

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
  • Oxazole histone deacetylase inhibitor and preparation method thereof
  • Oxazole histone deacetylase inhibitor and preparation method thereof
  • Oxazole histone deacetylase inhibitor and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] This embodiment provides a method for preparing an oxazole histone deacetylase inhibitor, comprising the following steps:

[0034] S1), respectively put 15mmol of hydroxylamine hydrochloride and 15mmol of KOH in a round bottom flask, add 25mL of anhydrous methanol to dissolve, stir in an ice bath for 30min and filter to obtain potassium hydroxylamine (NH 2 OK) solution, sealed for subsequent use;

[0035] S2), 1mmol of 7-(5-phenyloxazole-2-amide) heptanoic acid methyl ester was prepared in advance with 25mLNH 2 The OK solution was dissolved, and 20 mmol of hydroxylamine was added, and after stirring at room temperature for 1 h, the end point of the reaction was detected by TCL, and the solvent was removed under reduced pressure;

[0036] S3), add an appropriate amount of 2mol / L hydrochloric acid solution to acidify to PH=3-4, extract with dichloromethane (3×20mL), anhydrous MgSO 4 Dry and evaporate to dryness to obtain the crude product, denoted as 10d.

[0037] Pres...

Embodiment 2

[0042] This embodiment provides a method for preparing an oxazole histone deacetylase inhibitor, comprising the following steps:

[0043] S1) Put 15mmol of hydroxylamine hydrochloride and 15mmol of KOH in a round-bottomed flask respectively, add 25mL of anhydrous methanol to dissolve, stir in an ice bath for 30min, and filter to obtain hydroxylamine potassium (NH 2 OK) solution, sealed for future use.

[0044] S2), 1mmol of 7-(5-(4-methoxyphenyloxazole)-2-amide) methyl heptanoate was prepared in advance with 25mLNH 2 The OK solution was dissolved, and 20 mmol of hydroxylamine was added, and after stirring at room temperature for 1 h, the end point of the reaction was detected by TCL, and the solvent was removed under reduced pressure;

[0045] S3), add an appropriate amount of 2mol / L hydrochloric acid solution to acidify to PH=3-4, extract with dichloromethane (3×20mL), anhydrous MgSO 4 Dry and evaporate to dryness to obtain the crude product, recorded as 9g.

[0046] Prese...

Embodiment 3

[0051] This embodiment provides a method for preparing an oxazole histone deacetylase inhibitor, comprising the following steps:

[0052] S1), respectively put 15mmol of hydroxylamine hydrochloride and 15mmol of KOH in a round bottom flask, add 25mL of anhydrous methanol to dissolve, stir in an ice bath for 30min and filter to obtain potassium hydroxylamine (NH2 OK) solution, sealed for future use.

[0053] S2), 1mmol of 7-(5-(4-chlorophenyloxazole)-2-amide) methyl heptanoate was prepared in advance with 25mLNH 2 The OK solution was dissolved, and 20 mmol of hydroxylamine was added, and after stirring at room temperature for 1 h, the end point of the reaction was detected by TCL, and the solvent was removed under reduced pressure;

[0054] S3), add an appropriate amount of 2mol / L hydrochloric acid solution to acidify to PH=3-4, extract with dichloromethane (3×20mL), anhydrous MgSO 4 Dry and evaporate to dryness to obtain the crude product, denoted as 10m.

[0055] Present em...

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 an oxazole histone deacetylase inhibitor and a preparation method thereof. The preparation method is characterized by comprising the following steps: dissolving an oxazole compound 1A by using an NH2OK solution, adding hydroxylamine, stirring at room temperature, detecting a reaction endpoint by using TLC, removing a solvent under reduced pressure, adding a hydrochloric acidsolution for acidification, extracting by using dichloromethane, and drying by distillation to obtain a crude product; the oxazole compound provided by the invention has a very strong inhibition effect on histone deacetylase and cancer cells, and compared with histone deacetylase inhibitors on the market, the oxazole compound provided by the invention has the advantages that the activity of the oxazole compound on histone deacetylase is remarkably improved, has a better effect on solid tumors such as lung cancer, and can overcome the problems of low activity, poor curative effect on solid tumors and the like of the existing histone deacetylase inhibitor.

Description

technical field [0001] The invention relates to the technical field of new drug compounds, in particular to an oxazole histone deacetylase inhibitor and a preparation method thereof. Background technique [0002] Histone deacetylase (HDACs) is a kind of protease widely present in eukaryotic cells, which can remove the acetyl group on histone lysine, thereby inhibiting gene transcription. [0003] In addition, HDACs can also remove acetyl groups from some non-histone proteins, such as transcription factors, structural proteins and inflammatory mediators, affecting their functions. Inhibition of the enzymatic activity of HDACs can not only affect cellular processes such as gene expression, apoptosis, growth arrest, and differentiation, but also inhibit angiogenesis. Because HDACs play an extremely important role in gene expression and other cellular activities, HDAC inhibitors are of great research value in cancer treatment. [0004] Vorinostat is the first HDAC inhibitor ap...

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): C07D263/34A61P35/00
CPCC07D263/34A61P35/00Y02A50/30
Inventor 赵登高张瑞强马燕燕张焜莫华龙李冬利徐学涛盛钊君
Owner WUYI 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