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

Selective ER-beta receptor regulator and medicinal application thereof

A β-receptor and selective technology, which is applied in drug combinations, antineoplastic drugs, active ingredients of heterocyclic compounds, etc., can solve problems such as cross-resistance, poor selectivity, systemic side effects, etc.

Inactive Publication Date: 2017-11-24
FUDAN UNIV
View PDF8 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to provide novel selective ERβ receptor modulators, especially related to amine alkyl side chain class isopaucifloral F derivatives and the purposes for preparing

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
  • Selective ER-beta receptor regulator and medicinal application thereof
  • Selective ER-beta receptor regulator and medicinal application thereof
  • Selective ER-beta receptor regulator and medicinal application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Embodiment 1: Synthesis of amine alkyl side chain class isopaucifloral F derivatives

[0020]

[0021] Using 4-methoxyphenylmethylene diphenylphosphine oxide as the starting material to synthesize compound 2 through multi-step reactions (refer to the method explored by Sun Xun, Zhong Chen, etc.);

[0022] Compounds 1a-f, 1i-m: Weigh 0.2 mmol of compound 2 and dissolve in 15 mL of anhydrous dichloromethane under nitrogen protection. Add 3 mmol of boron tribromide ether solution under ice-cooling, slowly rise to room temperature and stir for 8 h, add a small amount of water to terminate the reaction. Dichloromethane was spin off, and saturated NaHCO 3 Aqueous solution to make the solution weakly alkaline, EA extraction, water and saturated NaCl solution washing, anhydrous NaCl 2 SO 4 dry. After concentrating the solvent, it was purified by reverse phase silica gel column chromatography (CH3CN:H2O=1:2,+0.1%TFA) to obtain light brown bubbly solids 1a-f, 1i-m;

[002...

Embodiment 2

[0061] Proliferation inhibitory effect of aminoalkyl side chain isopaucifloral F derivatives on human breast cancer cell lines MCF-7, MDA-MB-231 and human non-small cell lung cancer cell line A549

[0062] Experimental method: The in vitro antitumor activity of the complexes against MCF-7, MDA-MB-231 and A549 was determined by MTT method, and tamoxifen, raloxifene and isopaucifloral F were used as positive controls. Observe the inhibition of tumor cell growth by the drug at different concentrations, and calculate its half inhibition rate (IC50 value) to evaluate its anti-tumor activity in vitro;

[0063] Take cells in logarithmic growth phase and in good condition, add an appropriate amount of trypsin (purchased from GIBCO) to digest the cells, then remove the trypsin, wash with serum-containing culture medium to collect and resuspend the cells, count, and adjust the cell density. The cell suspension was inoculated on a 96-well plate (100 μL, 4000-5000 cells / well), at 37°C, 5%...

Embodiment 3

[0067] Example 3: Determination of ERβ binding ability and selectivity of compound (-)1n

[0068] This example adopts the radioligand binding assay experiment, radioligand-binding assay (radioligand-binding assay, RBA) is a classic method for testing the binding ability of ligands and receptors, which mainly uses The specific binding between the receptor and the receptor is used to study the affinity of the receptor, the number of the receptor and the subtype of the receptor. Usually, as long as a certain amount of radiolabeled ligand and the compound to be tested are incubated with the receptor to form a receptor-ligand complex, the complex is removed and then the amount of free radioactive ligand is measured, the compound and the compound can be deduced. Receptor affinity. In the current research on estrogen receptor ligands, the selectivity of compounds to a single receptor is mainly measured by this method.

[0069] In this example, the maximum binding ability of compound...

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 technical fields of medicinal chemistry and medicine, and particularly relates to a novel selective ER-beta receptor regulator and medicinal application thereof. The invention provides aminoalkyl side-chain-type isopaucifloral F derivatives disclosed as Formula (1) and application thereof in preparing a selective ER-beta receptor regulator. The regulator can overcome the defects of poor selectivity for receptor subtypes, cross resistance and systemic side effects when the existing estrogen receptor regulator drug is used for treating mammary cancer, and can be used for preparing drugs for resisting mammary cancer, prostatic cancer, ovarian cancer, colon cancer or non-small cell lung cancer.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and medicine, and specifically relates to a novel selective ERβ receptor modulator and its medicinal use. Background technique [0002] According to reports, malignant tumors are currently one of the main causes of threats to human health and death. The latest WHO World Cancer Report shows that in 2012, the number of cancer cases in China was 3.065 million, accounting for about one-fifth of the global incidence; the number of cancer deaths was 2.205 million, accounting for about one-quarter of the global cancer deaths. At present, the common clinical anti-tumor drugs include cytotoxic drugs, targeted therapy drugs, endocrine therapy drugs, etc. Among them, cytotoxic drugs have a significant effect on killing tumor cells, but they do not have targeting and are highly toxic; while targeted drug therapy drugs Most of them are monoclonal antibody drugs. Although the toxicity and side effec...

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): C07D295/088C07D211/14C07D217/04A61K31/4453A61K31/40A61K31/445A61K31/495A61K31/5375A61K31/472A61P35/00
Inventor 孙逊刘希希钟晨郝晓东唐美麟蒋喆
Owner FUDAN 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