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

Biphenyl benzimidazole azasugar derivative as well as synthesis method and application thereof

A biphenylbenzimidazole, a synthetic method technology, applied in the direction of drug combination, organic chemical method, bulk chemical production, etc., to achieve high efficiency of the preparation method, superior β-glucosidase inhibitory activity, and strong anti-glucosidase abnormality Related disease effects caused by expression

Active Publication Date: 2021-07-16
HEBEI UNIVERSITY
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there has been a lot of work on the structural modification of monocyclic and bicyclic azasaccharides and the study of structure-activity relationships, but the research on condensed azasaccharides is mostly limited to the study of synthetic methods (Yadav, L.D.S., et al., Carbohydr. Res. ,2010,345,318-323.), but there are few reports on its biological activity and structural modification

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
  • Biphenyl benzimidazole azasugar derivative as well as synthesis method and application thereof
  • Biphenyl benzimidazole azasugar derivative as well as synthesis method and application thereof
  • Biphenyl benzimidazole azasugar derivative as well as synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Synthesis of (3aR,4R,11bS)-9-bromo-2,2-dimethyl-3a,4,5,11b-tetrahydrobenzo[4,5]imidazol[1,2-a][1,3 ]dioxo[4,5-c]pyridin-4-ol (referred to as compound 3) and (3aR,4R,11bS)-8-bromo-2,2-dimethyl-3a,4,5,11b- Tetrahydrobenzo[4,5]imidazol[1,2-a][1,3]dioxo[4,5-c]pyridin-4-ol (Compound 4 for short)

[0035] Its chemical reaction process is as follows:

[0036]

[0037] The specific method is:

[0038] Weigh D-ribose 1 (4.3g, 12.5mmol) protected by propylidene and p-tosylated (Tsylated), commercially available or D-ribose as raw material, refer to the literature method Aravind, A., et al. , Eur.J.Org.Chem., 2011,83,6980-6988) and 4-bromo-1,2-o-phenylenediamine (2.79g, 1.2 equivalents, commercially available) in a 250mL flask, add 80mL The toluene was stirred and dissolved, and scandium trifluoromethanesulfonate (0.62 g, 0.1 equivalent, commercially available) was weighed, and the temperature of the oil bath was raised to 80° C. under nitrogen protection. After 10 h, as mo...

Embodiment 2

[0042] Synthesis of (3aR,4R,11bS)-9-(3,4-dimethoxyphenyl)-2,2-dimethyl-3a,4,5,11b-tetrahydrobenzo[4,5]imidazole And[1,2-a][1,3]dioxo[4,5-c]pyridin-4-ol (compound 6a for short)

[0043] Its chemical reaction process is as follows:

[0044]

[0045] The specific method is:

[0046] Weigh compound 3 (0.3g, 0.9mmol) and 3,4-dimethoxyphenylboronic acid (0.19g, 1.2 equivalents, commercially available) in a 25mL flask, add water and 1,4-dioxane 7mL was used as solvent, cesium carbonate (0.87g, 3.0 equivalents) was added, vacuumed, filled with nitrogen, and then pd(ppf)Cl was added 2 (0.07g, 0.1 equivalent, commercially available), vacuumize, fill with nitrogen, heat up to 95°C for reaction, TLC monitors that the reaction of raw material compound 3 is complete, extract with water and ethyl acetate, take the organic phase, dry over anhydrous sodium sulfate, reduce Pressure evaporated to remove solvent, 300 mesh silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =2:1), the product...

Embodiment 3

[0049] Synthesis of (2R,3R,4S)-7-(3,4-dimethoxyphenyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a] Pyridine-2,3,4-triol (compound 7a for short)

[0050] Its chemical reaction process is as follows:

[0051]

[0052] The specific method is:

[0053] Weigh compound 6a (0.26 g, 0.66 mmol) into a 25 mL flask, add 4 mL of 30% trifluoroacetic acid aqueous solution to dissolve. The reaction was carried out at room temperature under the protection of nitrogen. After 5 hours of reaction, TLC monitored that the reaction of the raw materials was complete. Sodium bicarbonate neutralizes the reaction solution, removes the salt by suction filtration, evaporates the solvent under reduced pressure from the filtrate, and separates by chromatography on a 200-mesh silica gel column (V 二氯甲烷 :V 甲醇 =15:1), a white solid 7a was obtained.

[0054] Compound 7a: white solid, yield 50%. (c 1mg / mL, CH 3 OH). 1 H NMR (400MHz, DMSO-d 6 )δ(ppm):7.82-7.75(m,1H),7.61(dd,J=8.4,2.0Hz,1H),7.52-7.47(m...

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 provides a biphenyl benzimidazo azasugar derivative as well as a synthesis method and application thereof. The derivative has a structure as shown in a formula (I) or (II) defined in the description. The invention discloses a preparation method of the biphenyl benzimidazo azasugar derivative and beta-glucosidase resisting activity of the biphenyl benzimidazo azasugar derivative. The compound is prepared by taking D-ribose protected by propylidene and subjected to p-toluenesulfonylation and 4-bromine-1, 2-o-phenylenediamine as raw materials and taking benzimidazole cyclization and Suzuki coupling as key reactions. The preparation method is efficient, simple and convenient. The compound has excellent beta-glucosidase inhibitory activity and a very strong effect on resisting related diseases caused by abnormal expression of glycosidase.

Description

technical field [0001] The present invention relates to azasaccharide derivatives and their synthesis methods and applications, in particular to a biphenyl benzimidazoloazepine derivatives and their synthesis methods and applications. Background technique [0002] Carbohydrates widely exist on the surface of various cells, and are the main factors for transmitting information between cells. They play an important role in cell signal transduction, information recognition, and physiological processes such as division, proliferation, and migration. Glycosidases act as specific glycosidic bond hydrolysis enzyme Directly involved in the glycosylation process, the occurrence and development of many major diseases such as diabetes, tumors, viral infections, and immune diseases are closely related to the abnormal expression of glycosidases (Hudak, J.E., et al., Chem.Biol., 2013, 21, 16-37.). For example, the abnormal expression of acid β-glucosidase, α-galactosidase, etc. will cau...

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): C07D471/04A61P3/10A61P35/00A61P31/12A61P37/02
CPCC07D471/04A61P3/10A61P35/00A61P31/12A61P37/02C07B2200/07Y02P20/55
Inventor 陈华苏路路李丰兴刘旭徐晓明王鑫李妍
Owner HEBEI UNIVERSITY
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