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Biphenyl benzimidazoloazepine derivatives and their synthesis methods and applications

A technology of biphenyl benzimidazole and synthesis method, which is applied in the directions of drug combination, organic chemical method, bulk chemical production, etc., to achieve high efficiency of preparation method, superior β-glucosidase inhibitory activity, and strong anti-glucosidase abnormality Effects of expression-induced related diseases

Active Publication Date: 2022-01-11
HEBEI UNIVERSITY
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  • 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

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  • Biphenyl benzimidazoloazepine derivatives and their synthesis methods and applications
  • Biphenyl benzimidazoloazepine derivatives and their synthesis methods and applications
  • Biphenyl benzimidazoloazepine derivatives and their synthesis methods and applications

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Experimental program
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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 (4.3 g, 12.5 mmol, commercially available or using D-ribose as raw material, which is protected by propylidene and p-tosylated (Tsylated), 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. ...

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...

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Abstract

The invention provides a biphenyl benzimidazoloazepine derivative and its synthesis method and application. The derivative has the structure shown in formula (I) or (II). The invention discloses a biphenyl Preparation method of phenylbenzimidazoloazepine derivatives and their anti-β-glucosidase activity. This type of compound is prepared from propylidene-protected and p-tosylated D-ribose and 4-bromo-1,2-o-phenylenediamine as raw materials, and is prepared by the key reaction of benzimidazole ring formation and Suzuki coupling. The preparation method of the invention is efficient and simple. The compounds have superior β-glucosidase inhibitory activity and strong anti-glucosidase related diseases caused by abnormal expression.

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

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Application Information

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Patent Type & Authority Patents(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
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