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

HDAC/MAO-B dual inhibitor and preparation and application thereof

A technology of dual inhibitors and medicinal salts, applied in the preparation of carboxylic acid amides, organic compounds, anti-inflammatory agents, etc., can solve the problems of incomplete elucidation and complex pathogenesis of diseases

Pending Publication Date: 2022-01-21
HANGZHOU NORMAL UNIVERSITY
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The pathogenesis of AD is very complex, and the pathogenesis of the disease has not yet been fully elucidated

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
  • HDAC/MAO-B dual inhibitor and preparation and application thereof
  • HDAC/MAO-B dual inhibitor and preparation and application thereof
  • HDAC/MAO-B dual inhibitor and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1: the preparation of 4-((benzyl (propargyl) amine) methyl)-N-hydroxybenzamide (compound I 1 ) preparation

[0044]

[0045] Benzylamine (964mg, 9mmol), potassium carbonate (622mg, 4.5mmol) and N,N-dimethylformamide DMF (10mL) were sequentially added to a 50mL round bottom flask equipped with a magnetic stirrer, and stirred at room temperature. Subsequently, a solution of propyne bromide (1,536 mg, 4.5 mmol) in N,N-dimethylformamide (10 mL) was slowly added dropwise using a constant pressure dropping funnel, and the reaction was continued at room temperature after the addition was complete. The progress of the reaction was monitored by TLC, and the developing solvent was n-hexane:ethyl acetate (volume ratio 3:2). After the reaction, add water (20mL) to the reaction solution, extract with ethyl acetate (20mL×3), then wash the organic phase with water (20mL×2), saturated brine (20mL×2), anhydrous sodium sulfate After drying, the solvent was distilled off und...

Embodiment 2

[0048] Embodiment 2: N-hydroxyl-4-(((2-methylbenzyl) (propargyl) amine) methyl) benzamide (compound I 2 ) preparation

[0049]

[0050] Benzylamine is replaced by 2-methylbenzylamine, and compound I is obtained with reference to the synthetic method of Example 1 2 (29%), white solid, melting point is 112.1-112.9°C. 1 H-NMR (400MHz, DMSO-d 6 )δ11.17(s,1H),9.00(s,1H),7.71(d,J=8.0Hz,2H),7.38(d,J=8.0Hz,2H),7.31-7.29(m,1H), 7.17-7.13(m,3H),3.67(s,2H),3.62(s,2H),3.27(t,J=2.2Hz,1H),3.12(d,J=2.0Hz,2H),2.31(s ,3H). 13 C-NMR (100MHz, DMSO-d 6 )δ164.2, 141.8, 137.2, 136.1, 131.7, 130.2, 129.6, 128.6, 127.3, 126.9, 125.6, 78.2, 76.5, 56.5, 55.1, 40.5, 18.8. HRMS (ESI) calcd for C 19 h 21 N 2 o 2 309.1598[M+H] + , found 309.1583.

Embodiment 3

[0051] Example 3: 4-(((4-fluorobenzyl)(propargyl)amine)methyl)-N-hydroxybenzamide (compound I 3 ) preparation

[0052]

[0053] Benzylamine is replaced by 4-fluorobenzylamine, and compound I is obtained with reference to the synthetic method of Example 1 3 (42%), light brown solid, melting point is 135.9-137.0℃. 1 H-NMR (400MHz, DMSO-d 6 )δ11.19(s,1H),9.02(s,1H),7.72(d,J=8Hz,2H),7.43-7.37(m,4H),7.19-7.14(m,2H),3.65(s, 2H), 3.60(s, 2H), 3.26(d, J=2.0Hz, 1H), 3.17(d, J=2.0Hz, 2H).13C NMR(100MHz, DMSO-d 6 )δ164.2,161.4(d, 1 J=241.2Hz), 141.9, 134.5(d, 4 J=2.9Hz), 131.7, 130.5(d, 3 J=8.0Hz), 128.5, 127.0, 115.1 (d, 2 J=21Hz), 78.2, 76.6, 56.3, 55.9, 40.8. HRMS (ESI) calcd for C 18 h 18 FN 2 o 2 313.1347[M+H]+, found 313.1340.

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 discloses an HDAC / MAO-B dual inhibitor, preparation thereof and application of the HDAC / MAO-B dual inhibitor in preparation of drugs and neuroprotective antioxidants for preventing and treating related diseases by inhibiting monoamine oxidase and histone deacetylase. The HDAC / MAO-B dual inhibitor has the following general formula (I) or (II), wherein in the formula (I) and the formula (II), R is respectively and independently an aromatic group or a substituted aromatic group. The HDAC / MAO-B dual inhibitor not only has an HDAC inhibition effect, but also has an MAO-B inhibition effect, and is a multi-target hydroxamic acid / anthranilamide propargylamine type derivative which realizes nerve protection and oxidation resistance through cooperation of a propargylamine group and hydroxamic acid or anthranilamide group.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to HDAC / MAO-B dual inhibitors and their preparation and application. Background technique [0002] Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by abnormal deposition of amyloid β peptide and microtubule-associated protein tau. It is the most common form of dementia in the elderly. It accounts for 60%-70% of people with dementia. The pathogenesis of AD is very complex, and the pathogenesis of this disease has not been fully elucidated yet. Among them, the cholinergic hypothesis, the β-amyloid protein theory, the abnormal phosphorylation theory of Tau protein, the metal ion hypothesis, the oxidative stress hypothesis, and the inflammation hypothesis are the main pathogenesis hypotheses. [0003] Monoamine oxidase (monoamine oxidase, MAO) is a metabolic enzyme containing flavin adenine dinucleotide, present in the mitochondrial outer membrane, ...

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): C07C259/10C07C237/40C07C231/12A61P25/28A61P25/16A61P29/00A61K31/167A61K31/166
CPCC07C259/10C07C237/40A61P25/28A61P25/16A61P29/00Y02P20/55
Inventor 白仁仁谢恬叶向阳姚传胜
Owner HANGZHOU NORMAL UNIVERSITY
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