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

Vinyl sulfonamide or vinyl amide compound and preparation method and application thereof

A compound and mixture technology, applied in the field of biomedicine, can solve the problems of poor selectivity, single skeleton, weak affinity, etc., and achieve the effect of clear mechanism of action, novel target and good physical and chemical properties

Inactive Publication Date: 2020-12-01
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing inhibitors targeting this pocket are only the non-steroidal anti-inflammatory analgesic drug flufenamic acid and its derivatives, which have weaker affinity than the substrate palmitic acid (K D =73μM), poor selectivity, and a single backbone, so it is still necessary to develop TEAD inhibitors with strong activity, good specificity, and clear mechanism of action to clarify the function of TEAD palmitoylation and provide new therapeutic methods for the treatment of Hippo pathway-related diseases

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
  • Vinyl sulfonamide or vinyl amide compound and preparation method and application thereof
  • Vinyl sulfonamide or vinyl amide compound and preparation method and application thereof
  • Vinyl sulfonamide or vinyl amide compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Example 1 Preparation of Compound DC-XHL-01

[0080]

[0081] Under ice-cooling, o-phenylphenol (50mg, 1 equivalent), triethylamine (44mg, 1.5 equivalents) were added to ultra-dry dichloromethane (20ml), and then diluted with ultra-dry dichloromethane (1ml) 2-Chloroethanesulfonyl chloride (57 mg, 1.2 equivalents) was slowly dropped into the reaction system. After reacting for 2 hours, TLC detected that the reaction of raw materials was complete, quenched with water, extracted with dichloromethane, washed the organic phase with saturated ammonium chloride solution twice, washed the organic phase with saturated brine once, dried the organic phase with anhydrous sodium sulfate, concentrated, The crude product was separated by column chromatography to obtain 54mg product. Characterization data: 1 H NMR (400MHz, Chloroform-d) δ7.50–7.43(m,5H),7.43–7.34(m,4H),6.03(d,J=16.4Hz,1H),5.81(dd,J=16.4,9.9 Hz,1H),5.69(d,J=9.9Hz,1H).

[0082] Wherein, the base triethylamine can ...

Embodiment 2-7

[0084] The compound of Example 2-7 was prepared by the same or similar method as that of Example 1. The specific compound structure and characterization data are as follows:

[0085]

[0086]

Embodiment 8

[0087] Embodiment 8: Preparation of compound DC-XHL-07

[0088] step 1:

[0089]

[0090] m-Tolylboronic acid (76mg, 1.2 equivalents), p-nitrobenzyl bromide (100mg, 1 equivalent), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (7mg, 0.02 equivalent) was added to the solution of 1,2-dichloroethane 1,2-dichloroethane:2M sodium carbonate (V:V)=3:1, and gas exchanged with argon three times. The reaction was reacted in an oil bath at 90°C for two hours. After the reaction of the raw materials was detected by TLC, the reaction solution was diluted with dichloromethane, extracted with water, the organic phase was washed with saturated brine, the organic phase was collected, concentrated, and the crude product was separated by column chromatography to obtain 96mg product. Characterization data: 1 H NMR (400MHz, Chloroform-d) δ8.18–8.10(m,2H),7.37–7.31(m,2H),7.24–7.17(m,1H),7.07(d,J=7.6Hz,1H), 6.98(d, J=7.3Hz, 2H), 4.04(s, 2H), 2.33(s, 3H).

[0091] Wherein the alka...

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 a vinyl sulfonamide or vinyl amide compound and a preparation method and application thereof. The structure of the vinyl sulfonamide or vinyl amide compound is as shown in a formula I, and in the formula, the definition of each substituent is as shown in the specification and claims. The compound can be used for preparing medicines for treating diseases or symptoms mediatedby TEADs.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a multi-substitution target transcription factor TEADs family self-palmitoylation activity inhibitory compound, a preparation method, a pharmaceutical composition and an application thereof. Background technique [0002] The TEA domain transcription factor TEAD is the end effector of the Hippo signaling pathway, which plays an important role in cell growth, organ size control and embryonic development. In mammalian cells, the TEAD family contains four homologous proteins of TEAD1-4, and the overall homology is about 61%-73%. TEAD1 promotes the expression of specific genes in the heart and plays an important role in the differentiation of cardiomyocytes. TEAD2 mainly regulates gene expression during neurodevelopment. TEAD4 is mainly related to embryo implantation. However, the specific function of TEAD3 is still not very clear. All tissues express at least one TEAD, and some express...

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): C07C309/67C07C311/11C07D217/06C07D217/02C07C323/48A61P35/00A61P35/02A61P9/00A61P25/28A61P29/00A61P19/08A61P3/10A61P13/12A61P11/00A61K31/472A61K31/255A61K31/145
CPCA61P3/10A61P9/00A61P11/00A61P13/12A61P19/08A61P25/28A61P29/00A61P35/00A61P35/02C07C309/67C07C311/11C07C323/48C07D217/02C07D217/06C07C2601/14Y02A50/30
Inventor 罗成周兵陆文超王军李勇杨亚玺丁宏陶泓儒陈凯先蒋华良
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com