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

Amide compound, preparation method and medical use thereof

A compound, benzamide technology, applied in the field of medicinal chemistry, can solve the problems of low activity of small molecule inhibitors, poor membrane permeability, poor physical and chemical properties of peptidomimetic compounds, etc.

Active Publication Date: 2017-06-16
CHINA PHARM UNIV
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, research on inhibitors of MLL1-WDR5 protein-protein interaction is still in its infancy. The only inhibitors under research are peptidomimetics and a class of small molecule compounds, but peptidomimetic compounds have poor physical and chemical properties and poor membrane permeability. Poor, small molecule inhibitor activity is not high

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
  • Amide compound, preparation method and medical use thereof
  • Amide compound, preparation method and medical use thereof
  • Amide compound, preparation method and medical use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Synthesis of N-(2-(4-methylpiperazine)-5-cyanophenyl)-2-chloro-3-methoxybenzenesulfonamide (1):

[0043] Dissolve 1.0g (6.4mmol) of 2-fluoro-5-cyanoaniline in anhydrous dichloromethane in a 25ml eggplant-shaped flask, and add 2.3g (9.6mmol) of 2-chloro-3-methyl dropwise at room temperature. Add 0.77ml (9.6mmol) of pyridine to the dichloromethane solution of oxybenzenesulfonyl chloride and react at room temperature overnight. The reaction solution was spin-dried by column chromatography to obtain the intermediate E as a pale yellow solid 0.97 g (yield 48.5%).

[0044] Put 0.2g (0.61mmol) of the above solid in a 25ml eggplant-shaped flask, dissolve it in 5ml DMF, add 0.088ml (0.8mmol) N-methylpiperazine, then add 0.14ml (0.8mmol) DIPEA catalyst, and react at 80℃ After 3 hours, the reaction solution was diluted with 40 ml of ethyl acetate, washed twice with water, and the organic phase was collected by column chromatography to obtain 10.15 g of light yellow solid (yield: 60.1%...

Embodiment 2

[0047] Synthesis of N-(2-Fluoro-4-methoxyphenyl)-2-(4-methylhomopiperazine)-5-cyanophenylsulfonamide (2):

[0048] Using 2-fluoro-5-cyanobenzenesulfonyl chloride, 2-fluoro-4-methoxyaniline, and N-methylhomopiperazine as raw materials, according to the similar method of Example 1, compound 2 was synthesized and obtained in two steps. The rate is 30.5%.

[0049] 1 H NMR(300MHz, CDCl 3 )δ8.22(s,1H),7.91(s,1H),7.81(d,J=7.3Hz,1H), 7.08(d,J=8.4Hz,1H), 6.98(d,J=7.7Hz, 2H), 5.28 (br s, 1H), 3.86 (s, 3H), 3.28 (t, J = 4.3 Hz, 4H), 3.02 (m, 2H), 2.90 (m, 2H), 2.70 (s, 3H) ,1.87(m,2H).

Embodiment 3

[0051] Synthesis of N-(2-(4-methylpiperazine)-5-trifluoromethylphenyl)-2,4,6-trimethylbenzenesulfonamide (3):

[0052] Using 2-fluoro-5-trifluoromethylaniline, 2,4,6-trimethylbenzenesulfonyl chloride and N-methylpiperazine as raw materials, according to the similar method of Example 1, compound 3 was synthesized, two steps The yield was 29.2%.

[0053] 1 H NMR(300MHz, CDCl 3 )δ7.98(d,J=2.5Hz,1H), 7.86(dd,J=8.7,2.5Hz,2H), 7.23(d,J=8.7Hz,1H), 6.98(s,2H),3.01( br s, 4H), 2.73 (br s, 10H), 2.50 (br s, 4H), 2.48 (s, 3H), 2.28 (s, 3H).

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 present invention relates to the field of medicinal chemistry, in particular to a group of amide compounds (I) and their preparation methods and applications. Pharmacodynamic tests have proved that the compounds of the present invention can be used to prepare medicines for treating leukemia.

Description

Technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a group of amide compounds and their preparation methods and uses. The compounds of the invention can be used to prepare drugs for treating leukemia. Background technique [0002] The gene translocation of the 4-position lysine (H3K4) methyltransferase MLL1 of histone H3 is rearranged to form a fusion gene, expressing MLL fusion protein, MLL fusion protein can cause acute myeloid leukemia (AML) and acute lymphatic Mixed lineage leukemia including leukemia (ALL). Among them, leukemia caused by abnormal MLL1 accounts for 5-10% of adult AML leukemias, and 70% of neonatal ALL leukemias. MLL leukemia has unique clinical characteristics, conventional chemotherapy is not ideal, and the prognosis is poor. Therefore, it is necessary to develop new treatment methods and drugs for the biological properties of leukemia caused by abnormal MLL. The occurrence of mixed lineage leukemia requires ...

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 Patents(China)
IPC IPC(8): C07C255/60C07C253/30C07C237/40C07C231/14C07C233/80C07D295/155C07D243/08C07D295/096C07D295/135C07D213/74C07D295/13C07D233/61C07D239/26C07D213/56C07C279/12C07C277/08A61K31/495A61K31/551A61K31/277A61K31/167A61K31/496A61K31/40A61K31/506A61P35/02
Inventor 尤启冬孙昊鹏李冬冬陈维琳郭小可张晓进徐晓莉
Owner CHINA PHARM 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