Compounds for inducing mesenchymal stem cells to differentiate into cartilage and application of compounds

A compound and oxide technology, applied in animal cells, vertebrate cells, bone/connective tissue cells, etc., can solve problems such as low efficiency

Pending Publication Date: 2022-07-19
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, MSCs still have many problems in tissue regeneration and repair. The main problem in articular cartilage regeneration and repair is that the efficiency of MSCs transplanted into the body to truly differentiate into chondrocytes is very low
However, follow-up studies found that KGN alone could not induce 3D cultured stem cell cartilage to form smooth, compact spherical cell structures in vitro.

Method used

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  • Compounds for inducing mesenchymal stem cells to differentiate into cartilage and application of compounds
  • Compounds for inducing mesenchymal stem cells to differentiate into cartilage and application of compounds
  • Compounds for inducing mesenchymal stem cells to differentiate into cartilage and application of compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0121] Example 1: Preparation of compounds

Embodiment 1-1

[0122] Example 1-1. Preparation of 5-bromo-N-(5-chloro-2-(2-methoxyethoxy)phenyl)thiophene-2-carboxamide (GCP001)

[0123] 4-Chloro-2-nitrophenol (1.74 g, 10 mmol), 2-bromoethyl methyl ether (4.17 g, 30 mmol), potassium carbonate (4.14 g, 30 mmol) were dissolved in N,N-dimethylmethane amide (30 mL) at 80°C for 2 hours. After the completion of the reaction was detected by TLC, the reaction solution was extracted with ethyl acetate, the organic phase was washed twice with water, once with saturated brine, and dried over anhydrous sodium sulfate. After the organic phase was evaporated to dryness, the compound was separated and purified by column chromatography to obtain compound 4-chloro-1-(2-methoxyethoxy)-2-nitrobenzene (2.2 g, yield 95%).

[0124] 4-Chloro-1-(2-methoxyethoxy)-2-nitrobenzene (2.2 g, 9.5 mmol) was dissolved in methanol (30 mL), palladium carbon was added, hydrogen was passed through, and the reaction was carried out at room temperature for 2 hours . After the...

Embodiment 1-2

[0127] Example 1-2, Preparation of 3-chloro-N-(5-chloro-2-(2-methoxyethoxy)phenyl)thiophene-2-carboxamide (GCP002)

[0128] Using a method similar to the preparation of compound GCP001, 5-bromo-2-carboxythiophene was replaced with 3-chlorothiophene-2-carboxylic acid, and finally compound GCP002 was obtained with a yield of 80%.

[0129] 1 H NMR (CDCl 3 , 300MHz): 9.62(s, 1H), 8.58(s, 1H), 7.51(d, J=5.1Hz, 1H), 7.06-6.95(m, 2H), 6.85(d, J=5.1Hz, 1H) , 4.18 (t, J=4.2Hz, 2H), 3.76 (t, J=4.2Hz, 2H), 3.41 (s, 3H).

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PUM

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Abstract

The invention relates to a compound for inducing mesenchymal stem cells to differentiate into cartilage and application of the compound, and discloses a small molecule compound represented by structural formulas (I)-(VI) or pharmaceutically acceptable salt, solvate, polymorphic substance, prodrug, ester, metabolite, N-oxide, stereoisomer or isomer of the small molecule compound, as well as pharmaceutical compositions containing such compounds and methods of preparation thereof. The small molecule compound and pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, esters, metabolites, N-oxides, stereoisomers or isomers or pharmaceutical compositions thereof can be used for improving osteoarthritis or joint injury related diseases by inducing chondrogenic differentiation of endogenous mesenchymal stem cells. The method can be used for inducing chondrogenic differentiation of the mesenchymal stem cells in vitro and enhancing the in-vivo cartilage repair effect of the stem cells, so that osteoarthritis or joint injury and / or symptoms related to arthritis or joint injury are treated, prevented or improved.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to a class of compounds for inducing mesenchymal stem cells to differentiate into cartilage and applications thereof. Background technique [0002] Osteoarthritis (OA) is a degenerative joint disease that seriously affects the quality of life of patients. The main pathological features include articular cartilage degeneration and destruction, subchondral bone sclerosis or cystic degeneration, joint edge bone hyperplasia, synovial lesions, etc. , resulting in limited activity, which is more common in middle-aged and elderly people and athletes. According to the statistics of the World Health Organization (WHO), the prevalence of OA in people over 55 years old is about 80%, and almost all elderly people over 60 years old suffer from different degrees of bone and joint diseases (Bijlsma JW.et al.doi:10.1016 / S0140-6736(11)60243-2.(2011).). In addition, OA brings a heavy social burden...

Claims

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Application Information

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IPC IPC(8): C07D333/38C07D333/24C07D307/68C07D213/81C07D217/26C07C233/75C07C233/29C07C233/60A61P19/02A61P29/00A61P19/08A61K31/381A61K31/4402A61K31/472A61K31/167A61K31/341C12N5/0775C12N5/077
CPCC07D333/38C07D333/24C07D307/68C07D213/81C07D217/26C07C233/75C07C233/29C07C233/60A61P19/02A61P29/00A61P19/08C12N5/0655C07C2601/02C12N2506/1353C12N2506/1369C12N2506/1384C12N2506/1392C12N2501/999
Inventor 罗剑陈益华高竞铎吕方裴海翔刘明耀
Owner EAST CHINA NORMAL UNIVERSITY
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