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

Compound with benzimidazole structure and preparation method and application thereof

A compound, benzo technology, applied in the field of medicine, can solve the problems of poor selectivity, lack of structural novelty and diversity, and small quantity, and achieve the effect of high activity in vivo

Pending Publication Date: 2021-06-08
CHINA PHARM UNIV
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the existing BChE inhibitors are accompanied by the emergence of AChE inhibitors, which have the disadvantages of small number, lack of structural novelty and diversity, and poor selectivity.

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 benzimidazole structure and preparation method and application thereof
  • Compound with benzimidazole structure and preparation method and application thereof
  • Compound with benzimidazole structure and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] (1) Synthesis of 4-(1H-benzo[d]imidazol-2-yl)-1,2,5-oxadiazol-3-amine (Intermediate 1)

[0034]Take 2-cyanomethylbenzimidazole (1g, 6.36mmol) in an eggplant-shaped bottle, dissolve it with acetic acid (10ml), add an aqueous solution of sodium nitrite (0.44g, 6.36mmol) dropwise under an ice bath, and a solid is formed, After stirring in an ice bath for 40 minutes, it was suction filtered, and the filter cake was washed once with water and twice with diethyl ether. Take another eggplant-shaped bottle, add hydroxylamine hydrochloride (0.53g, 7.63mmol) in an ice bath, add water as a solvent, add potassium hydroxide (0.54g, 9.54mmol), and then add diglyme (6ml) , and finally add the filter cake of the previous step, return the reaction system to room temperature and start heating, reflux for 6 hours, and cool to room temperature; a large number of golden pink crystals precipitate, filter with suction, wash the filter cake once with water, wash twice with ether, and dry to ob...

Embodiment 2

[0042] 2-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1H-benzo[d]imidazol-1-yl)-N-(3-(pyrrolidin-1- Base) the synthesis of phenylacetamide:

[0043] With reference to the synthetic method of Example 1, the 3-aminobenzoic acid in Example 1 is replaced by 3-(pyrrolidin-1-yl)aniline to obtain a brownish black solid compound, which is 2-(2-(4-amino- 1,2,5-oxadiazol-3-yl)-1H-benzo[d]imidazol-1-yl)-N-(3-(pyrrolidin-1-yl)phenylacetamide (compound 2) .TLC detection is one point, there are dark spots under the ultraviolet lamp at 254nm, and there is no fluorescence at 365nm. 1 H NMR (300MHz, DMSO-d6): δ10.37(s,1H,N H CO), 7.96-7.70 (m, 2H, ArH), 7.63-7.32 (m, 2H, ArH), 7.09 (t, J=8.1Hz, 1H, ArH), 7.04 (s, 2H, N H 2 ), 6.89(t, J=2.1Hz, 1H, ArH), 6.80(dd, J=7.7, 1.8Hz, 1H, ArH), 6.28(dd, J=8.2, 2.3Hz, 1H, ArH), 5.58( s,2H,C H 2 ),3.26-3.06(m,4H,C H 2 C H 2 ),2.15-1.82(m,4H,C H 2 C H 2 ).

Embodiment 3

[0045] 2-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1H-benzo[d]imidazol-1-yl)-N-(3-(piperidine-1- Base) phenyl) acetamide synthesis:

[0046] With reference to the synthetic method of Example 1, the 3-aminobenzoic acid in Example 1 is replaced by 3-(piperidin-1-yl)aniline to obtain a brown solid compound, which is 2-(2-(4-amino- 1,2,5-oxadiazol-3-yl)-1H-benzo[d]imidazol-1-yl)-N-(3-(piperidin-1-yl)phenyl)acetamide (compound 3 ). TLC detection is one point, there are dark spots under the ultraviolet lamp at 254nm, and there is no fluorescence at 365nm. 1 H NMR (300MHz, DMSO-d6): δ10.85(s,1H,N H CO),7.99(s,1H,ArH),7.88(dd,J=15.3,7.9Hz,2H,ArH),7.47(d,J=7.6Hz,2H,ArH),7.42(t,J=7.5Hz ,1H,ArH),7.30(d,J=24.6Hz,2H,ArH),7.05(s,2H,N H 2 ),5.65(s,2H,C H 2 ),3.47-3.38(m,4H,C H 2 C H 2 ), 1.81(t, J=5.8Hz, 4H, C H 2 C H 2 ),1.63(s,2H,C H 2 ).

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 compound with a benzimidazole structure and a preparation method and application thereof. The invention discloses a compound shown in a formula (I), and further discloses application of the compound in preparation of a medicine for preventing or treating Alzheimer's disease. The inventor uses butyrylcholine esterase inhibitory activity, selective screening and Morris water maze experiments as carriers to evaluate the compound shown in the formula (I) for treating the Alzheimer's disease (especially moderate and severe Alzheimer's disease), and finds that the compound has good in-vitro and in-vivo activity and extremely high selectivity, and can be used for preparing the compound for treating the Alzheimer's disease. The compound can be used as a precursor substance for further developing the effect of treating the Alzheimer's disease by selectively inhibiting butyrylcholine esterase.

Description

technical field [0001] The invention belongs to the field of medicine, and specifically relates to a class of compounds with a benzimidazole structure and a preparation method and use thereof. Background technique [0002] Alzheimer's disease (AD) is a systemic brain neurodegenerative syndrome, clinically manifested as central cognitive decline, mental and motor disorders. At present, with the aging of the population has become a global problem, AD has posed a huge threat to the life and health of the elderly and the overall medical resources of the society. According to the "World Alzheimer's Disease Report 2019", there were 50 million AD patients worldwide in 2019, and by 2050, this number will reach 152 million. In the past five years, global investment in AD treatment has increased by more than 35%, and has now exceeded one trillion US dollars. This series of shocking figures clearly reveals the severe situation of AD prevention and treatment at present, and it is urge...

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 Applications(China)
IPC IPC(8): C07D413/04A61K31/4245A61P25/28
CPCC07D413/04A61P25/28
Inventor 孙昊鹏邢帅帅熊柏晨李琦冯锋柳文媛陈颖王园园
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