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
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  • 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 addit

Method used

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  • 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

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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...

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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

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Application Information

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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
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