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

Compound with anti-osteoporosis activity and application thereof

A compound and composition technology, applied in the field of medicine and biology, can solve the problems of affecting bone strength, affecting long-term medication and compliance, etc., and achieve the effects of improving osteoporosis, inhibiting osteoclast differentiation, and promoting osteoblast differentiation.

Active Publication Date: 2019-04-19
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although currently marketed drugs for the treatment of osteoporosis are effective, most drugs have their limitations and side effects. For example, long-term use of bisphosphonates may affect bone strength. In addition, the use of bisphosphonates is also accompanied by nausea and vomiting. , diarrhea, gastric ulcer and other gastrointestinal reactions, osteonecrosis of the jaw, nephrotoxicity and acute allergy and other adverse reactions (Green, J., et al., Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary carecohort.BMJ,2010.341:p.c4444.), affecting its long-term medication and compliance

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
  • Compound with anti-osteoporosis activity and application thereof
  • Compound with anti-osteoporosis activity and application thereof
  • Compound with anti-osteoporosis activity and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1. Synthesis of 5-chloro-N-(4-methylpyridin-2-yl)furan-2-carboxamide (compound HX0001)

[0042]

[0043] Proceed as follows:

[0044] (1) Take 2-amino-4-methylpyridine (5.40g, 0.05mol) in a 100mL three-necked flask, add 40mL of dry tetrahydrofuran to dissolve;

[0045] (2) Add 5-chlorofuran-2-formyl chloride (8.15g, 0.05mol) in tetrahydrofuran solution dropwise to it at 0°C;

[0046] (3) After the addition is complete, add 4.2mL (0.06mol) of triethylamine, and stir at room temperature for 4h;

[0047] (4) After the reaction is completed, the solvent is evaporated,

[0048] (5) The residue was mixed with silica gel and column chromatography EA:PE (1:10) to obtain 8.40 g of pure white solid product with a yield of 71.1%.

[0049] The mass spectrum of HX0001 is as figure 1 As shown, the results show that the preparation results are correct.

Embodiment 2

[0050] Example 2. Cultivation of cells

[0051] Mouse osteoblasts MC3T3-E1 and human osteosarcoma U-2OS cells are adherent cells, and they are passaged once every 48 hours. After the cells are overgrown, discard the old medium, rinse the cells with PBS and discard, then add appropriate amount of trypsin, digestion with MC3T3-E1 for about 2min at room temperature, and digestion with U-2OS for 2min at 37℃, discard the digestion solution Immediately add α-MEM or Mc5A complete medium containing 10% FBS to inhibit the trypsin activity. Use an elbow pipette to repeatedly gently blow the cells in the culture flask to completely separate the cells from the bottom of the flask and pipette to disperse them into individual cells Suspension. Then inoculate the cell suspension in a new cell flask at a ratio of 1:3, then add an appropriate amount of complete medium, and put it in the incubator to continue culturing. Culture conditions: 37°C, 5% CO 2 .

[0052] Mouse monocyte macrophages RAW26...

Embodiment 3

[0053] Example 3. Determination of the dose-effect relationship of HX0001 on OPG / RANKL expression regulation screening model

[0054] The OPG / RANKL expression upregulator high-throughput screening model constructed in the laboratory was used for high-throughput screening. This model is based on transfecting the reporter gene plasmid pGL4.17-OPGp with the OPG promoter to control the expression of firefly luciferase into U-2OS cells to obtain a stable transfected cell line. The RANKL promoter will control the expression of Renilla luciferase The reporter gene plasmid pGL4.76-RANKLp was transfected into the above cell line, thereby obtaining a stable transfected cell line that integrates the two reporter genes pGL4.17-OPGp and pGL4.76-RANKLp, and named it U-2OS- UORP (UORP for short) (see CN201510240396.1). This stably transfected cell line can express firefly and Renilla luciferase, and their expression is regulated by the upstream regulatory sequences of OPG and RANKL, respective...

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 relates to a compound with anti-osteoporosis activity and application thereof. The invention discloses the in-vitro and in-vivo anti-osteoporosis pharmacological activity of the compound. The N-(pyridine-2-base) amide compound has a significant value in treatment and prevention of osteoporosis.

Description

Technical field [0001] The present invention belongs to the field of medical biotechnology, and specifically relates to a group of compounds with anti-osteoporosis activity and their applications. Background technique [0002] Osteoporosis (Osteoporosis, OP) is a systemic metabolic bone disease. In 1994, the World Health Organization defined osteoporosis as characterized by the destruction of the fine structure of bone and the decrease in bone mass, leading to increased bone fragility, A systemic bone disease prone to fractures (Canalis, E., Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches. Nat Rev Endocrinol, 2013.9(10): p.575-83.). In 2001, the National Institutes of Health redefined osteoporosis as a bone disease in which decreased bone strength leads to an increased risk of fracture (Clevers, H., Wnt / beta-catenin signaling in development and disease.Cell, 2006.127(3) :p. 469-80.). [0003] Conventional drugs that have been approved for the treatment...

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): C07D405/12C07D213/81C07D213/75C07D409/12A61P19/10A61K31/444A61K31/4436A61K31/443A61K31/44
CPCA61P19/10C07D213/75C07D213/81C07D405/12C07D409/12
Inventor 司书毅韩小婉许艳妮姜威宫世强贺晓波刘超王潇罗金雀左璇姜新海
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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