Nitrogen-atom double-substitution hydroxamic acid compound with oxadiazole structure as well as application and preparation method thereof

A technology of oxadiazoles and compounds, which is applied in the field of synthesis of nitrogen-atom double-substituted hydroxamic acid compounds, can solve the problem of unsatisfactory treatment effects on solid tumors, and achieve the effect of promoting acetylation levels

Active Publication Date: 2018-09-14
UNIV OF JINAN
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the HDACi currently on the market are all used for the treatment of hematological cancers, and the therapeutic effect on solid tumors is not very satisfactory. Therefore, the development of new HDACi for the treatment of solid tumors is now a more popular direction

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
  • Nitrogen-atom double-substitution hydroxamic acid compound with oxadiazole structure as well as application and preparation method thereof
  • Nitrogen-atom double-substitution hydroxamic acid compound with oxadiazole structure as well as application and preparation method thereof
  • Nitrogen-atom double-substitution hydroxamic acid compound with oxadiazole structure as well as application and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0043] Example 1-1, compound N 1 -Hydroxy-N 7 -(4-Methoxyphenyl)-N 7 Preparation of -((5-phenyl-1,2,4-oxadiazole-3-)methyl)pimelic amide (JX01)

[0044] Dissolve p-methylaniline (3.6 g, 30.0 mmol) in DMF, add potassium carbonate (4.1 g, 30.0 mmol), stir for half an hour, then add bromoacetonitrile (1.4 ml, 20.0 mmol), react at room temperature overnight, extract, overnight Column purification gave solid compound 2 (4 g).

[0045] Dissolve compound 2 (3.3 g, 20.0 mmol) in dioxane, add pimelic anhydride (4.3 g, 30.0 mmol), heat to reflux, neutralize acid and alkali after the reaction, evaporate to dryness to obtain compound 3, and directly carry out In the next step of esterification reaction, compound 4 (3.8 g) was purified.

[0046] Dissolve compound 4 (3.8 g, 12.0 mmol) and hydroxylamine hydrochloride (1.25 g, 17.9 mmol) in methanol / water, add sodium carbonate (954 mg, 9.0 mmol), reflux overnight, extract, and purify through a column to obtain a solid compound 5 (2.35 g,...

Embodiment 1-2

[0049] Embodiment 1-2, compound N 1 -Hydroxy-N 7 -(4-Methoxyphenyl)-N 7 Preparation of -((5-(o-fluorophenyl)-1,2,4-oxadiazole-3-)methyl)pimelic acid amide (JX02)

[0050] Replace benzoyl chloride with o-fluorobenzoyl chloride, and prepare JX02 according to the method for preparing compound JX01. 1 H NMR (600MHz, DMSO) δ 10.29 (brs, 1H), 8.64 (brs, 1H), 8.02 (dd, J = 7.2, 7.8 Hz, 1H),7.67-7.66 (m, 1H), 7.48 – 7.43 (m, 1H), 7.42 – 7.36 (m, 2H), 7.33 (dd, J =8.4, 9.0 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.98 (d, J = 7.8 Hz, 1H), 5.76(s, 2H), 3.78 (s, 3H), 2.07 (t, J = 7.8 Hz, 2H), 1.87-1.85 (m, 2H), 1.45-1.43(m, 2H), 1.39 – 1.36 (m, 2H), 1.14 – 1.10 (m, 2H).

Embodiment 1-3

[0051] Embodiment 1-3, compound N 1 -Hydroxy-N 7 -(4-Methoxyphenyl)-N 7 Preparation of -((5-(m-fluorophenyl)-1,2,4-oxadiazole-3-)methyl)pimelic acid amide (JX03)

[0052] Benzoyl chloride was replaced by m-fluorobenzoyl chloride, and JX03 was correspondingly prepared according to the method for preparing compound JX01. 1 H NMR (600MHz, DMSO) δ 10.31 (brs, 1H), 8.65 (brs, 1H), 7.96 (d, J = 7.8 Hz, 1H), 7.89(d, J = 9.0, 1H), 7.72-7.68 (m, 1H), 7.59 (td, J = 8.4, 2.4 Hz, 1H), 7.33 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 4.99 (s, 2H), 3.77 (s, 3H), 2.04(t, J = 7.2 Hz, 2H), 1.88 (t, J = 7.2 Hz, 2H), 1.48 – 1.42 (m, 2H), 1.41 –1.35 (m, 2H), 1.16 – 1.10 (m, 2H).

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 novel nitrogen-atom double-substitution hydroxamate histone deacetylase inhibitor with an oxadiazole structure. The novel nitrogen-atom double-substitution hydroxamate histonedeacetylase inhibitor is synthesized by taking a nitrogen-atom double-substitution structure with oxadiazole as a CAP zone and combining the nitrogen-atom double-substitution structure with a hydroxamic acid structure. The invention also provides application of the compound used as a novel histone deacetylase inhibitor. The invention further discloses application of the compound or pharmaceuticalcompositions thereof to preparation of medicines for treating diseases such as growth, metastasis and recurrence of various malignant tumors caused by histone acetylation disorder.

Description

technical field [0001] The invention relates to a histone deacetylase inhibitor, in particular to a synthesis method and application of a class of nitrogen-atom double-substituted hydroxamic acid compounds containing an oxadiazole structure. Background technique [0002] Histone deacetylase is an epigenetic enzyme involved in the regulation of the acetylation level of histone lysine residues. Epigenetics refers to the heritability of gene expression without changing the nucleotide sequence of the gene. Variety. Epigenetics mainly includes DNA modification (methylation) and histone modification (acetylation, phosphorylation, ubiquitination, etc.), among which the most studied is histone acetylation modification, including two enzymes: histone acetyltransferase (HAT) and histone deacetylase (HDAC), the function of HAT is to transfer the acetyl group to the lysine residue to prevent the charge interaction between histone and DNA base, make the chromosome loose, and facilitate ...

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): C07D271/06C07D413/04A61P35/00A61P35/02
CPCA61P35/00A61P35/02C07D271/06C07D413/04
Inventor 张华杨飞飞单佩佩赵娜周志侠张静
Owner UNIV OF JINAN
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap