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

Histone deacetylase inhibitor and preparation method and application thereof

A deacetylase and histone technology, applied in chemical instruments and methods, anti-inflammatory agents, drug combinations, etc., can solve the problems of cell necrosis, cell differentiation, cell apoptosis, etc., and achieve strong inhibitory effect and high selectivity. , active effect

Active Publication Date: 2017-01-11
杨思遥
View PDF11 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, many studies have confirmed that the treatment of tumor cells by FK228 leads to the inhibition of angiogenesis and cell growth, and at the same time induces apoptosis, cell necrosis and cell differentiation.

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
  • Histone deacetylase inhibitor and preparation method and application thereof
  • Histone deacetylase inhibitor and preparation method and application thereof
  • Histone deacetylase inhibitor and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Embodiment 1: The concrete preparation method of synthesizing CA101 comprises the following steps:

[0064] Step 1, prepare CA101-2:

[0065] The structural formula of CA101-2 is:

[0066] Weigh raw material CA101-1 (2.88g, 4.54mmol), the structural formula of CA101-1 is Place in a 50mL flask, add 25mL of redistilled dichloromethane, stir to dissolve all the solids, and then slowly add 5.76mL of trifluoroacetic acid dropwise. After the dropwise addition was completed, the reaction was stirred at room temperature for 2 hours, and the progress of the reaction was checked by spotting a TLC plate, and there was no raw material remaining. The reaction solution was spin-dried, then dissolved in toluene (5 mL×2) and spin-dried. Then, it was dried with a low-pressure oil pump for 1 hour to obtain a light brown transparent semi-solid, which was directly used in the next reaction without further purification.

[0067] Step 2, prepare CA101-4:

[0068] The structural formu...

Embodiment 2

[0088] Embodiment 2: the concrete preparation method of synthesizing CA102 comprises the following steps:

[0089] Step 1, prepare CA102-2:

[0090] The structural formula of CA102-2 is:

[0091] Get CA102-1 (2.4g, 8.2mmol), its structural formula is Dissolve it in 24mL of dichloromethane, then add 4.8mL of trifluoroacetic acid dropwise, and complete the addition within 10 minutes. After stirring at room temperature for 2 hours, it was spin-dried and banded twice with toluene (5 mL×2). After the oil pump is drained for 1 hour, it is directly cast to the next step.

[0092] Step 2 prepares CA102-3:

[0093] The structural formula of CA102-3 is:

[0094] Dissolve CA102-2 (1.57g, 8.2mmol) in 30mL of anhydrous N,N-dimethylformamide, at 0°C, add 1-ethyl-(3-dimethylaminopropyl)carbodi Imine hydrochloride (3.1g, 16.4mmol), 1-hydroxybenzotriazole (2.1g, 16.4mmol) and sodium bicarbonate (4.2g, 49.2mmol), then add N-Boc-alanine (1.87 g, 9.8 mmol), stirred at 0°C for 10 minut...

Embodiment 3

[0120] The concrete preparation method of synthetic CA103 comprises the following steps:

[0121] Dissolve CA102 (20 mg, 0.03 mmol) in 1 mL redistilled dichloromethane under nitrogen protection. Add Dess-Martin oxidizer (DMP) (34mg, 0.075mmol) under ice-bath at 0°C, stir at 0°C for 10 minutes, then at room temperature for 12 hours. After the reaction was monitored by TLC, cool down to 0°C, add 1 mL of dichloromethane to dilute, then add 1 mL of saturated sodium bicarbonate and 1 mL of 1M sodium thiosulfate successively, stir for 10 minutes and then separate the liquids, and use dichloromethane (3 mL× 3) Extract, combine the organic phases, wash with 3 mL of saturated brine, and dry over anhydrous sodium sulfate.

[0122] After spin-drying and passing through the column (DCM / MeOH=50 / 1), a colorless oil (CA103) was obtained, 15 mg, yield 75.4%.

[0123] CA103 NMR data:

[0124] 1 H NMR (400MHz, CDCl 3 )δ7.78(d, J=8.4Hz, 1H), 7.60(d, J=7.1Hz, 1H), 7.01(d, J=6.7Hz, 1H), 5.76–...

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 belongs to the field of an anticancer compound histone deacetylase inhibitor, and more specifically relates to a histone deacetylase inhibitor and a preparation method and an application thereof. A structural general formula is shown in the specification, wherein R1 and R2 are respectively selected from hydrogen, hydroxyl, siloxy or alkyloxy, or R1=R2=O; R3 is selected from hydrogen, triphenyl methyl sulfonium, p-methoxy-benzylthio, 2-(trimethylsilyl)ethylthio, 9-fluorenes methylthio, valeryl sulfenyl, hexanoyl sulfenyl, heptanoyl sulfenyl or capryloyl sulfenyl; and R4 is selected from triphenylmethyl, p-methoxybenzyl, 2-(trimethylsilyl)ethyl, 9-fluorenylmethyl, valeryl, hexanoyl, heptanoyl or capryloyl. The compound has little toxicity, is effected on specific molecular target, has the advantages of high selectivity, low side effect, intelligible effect mechanism, less objection, and especially has strong inhibition effect for colorectal cancer cells and breast cancer cells.

Description

technical field [0001] The invention relates to the field of anticancer compound histone deacetylase inhibitors, in particular to histone deacetylase inhibitors and their preparation methods and applications. Background technique [0002] Histone deacetylases (HDACs) are a series of zinc ion-dependent metalloproteases, which are involved in the modification and transformation of chromosome structure, regulation of gene transcription, and some important tumor suppressor factors such as p53 heat shock protein 90 and α-tubulin. The activity of proteins and cytokines plays a key role in tumorigenesis and is a new target for anti-tumor drug design in recent years. [0003] Histone deacetylase inhibitors (histone deacetylase inhibitors, HDACIs), referred to as HDACIs, are a series of compounds that interfere with the function of histone deacetylase, can effectively inhibit the proliferation of cancer cells, and induce cell apoptosis. Histone deacetylase inhibitors inhibit the pro...

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): C07K5/08A61K38/06A61P35/00A61P9/00A61P29/00A61P7/06A61P37/00A61P3/10A61P19/10A61P13/08A61P3/00
CPCA61K38/06C07K5/08Y02P20/55
Inventor 程义强杨思遥
Owner 杨思遥
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