CN110172052A - A kind of preparation process and application of chromone derivatives - Google Patents
A kind of preparation process and application of chromone derivatives Download PDFInfo
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- CN110172052A CN110172052A CN201910443775.9A CN201910443775A CN110172052A CN 110172052 A CN110172052 A CN 110172052A CN 201910443775 A CN201910443775 A CN 201910443775A CN 110172052 A CN110172052 A CN 110172052A
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- chromone derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
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- Diabetes (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The present invention relates to a kind of preparation process of chromone derivatives and applications, the preparation process includes the following steps: for 2- hydroxyl -6- methyl benzoic acid, propargyl alcohol to be dissolved in acetonitrile, after trifluoro-methane sulfonic acid silver (AgOTf) is added, it is heated to reflux temperature, chromone derivatives can be obtained in 8-10 hours in reaction；The structure of the chromone derivatives are as follows:
Description
Technical field
The invention belongs to pharmaceutical synthesis fields, and in particular to a kind of preparation process and application of chromone derivatives.
Background technique
Benzopyrone is a kind of important structural unit in organic matter, is chiefly used in pharmaceutical-chemical intermediate.Currently, benzo
The synthetic method multiplicity of pyranone structure, the present invention provides a kind of by being the effect of septichen and propargyl alcohol in AgOTf
Under, synthesize the preparation process of chromone derivatives.
Summary of the invention
The present invention provides a kind of preparation process for preparing chromone derivatives, it is characterised in that includes the following steps:
2- hydroxyl -6- methyl benzoic acid, propargyl alcohol are dissolved in acetonitrile, after trifluoro-methane sulfonic acid silver (AgOTf) is added, added
Chromone derivatives can be obtained in 8-10 hours in heat to reflux temperature, reaction；The structure of the chromone derivatives
Are as follows:
The preferred 1:1-1:1.5 of molar ratio of above-mentioned preparation process, 2- hydroxyl -6- methyl benzoic acid and propargyl alcohol；Acetonitrile
Dosage is advisable with can sufficiently dissolve reaction substrate, and preferably every mM of 2- hydroxyl -6- methyl benzoic acid uses 3-5mL acetonitrile；
The dosage of AgOTf is 0.8-1.0 times of 2- hydroxyl -6- methyl benzoic acid mole.
Another embodiment of the present invention provides a kind of chromone derivatives or its pharmaceutically acceptable salt, special
Sign is the structure of the chromone derivatives are as follows:
Another embodiment of the present invention provides above-mentioned chromone derivatives or its pharmaceutically acceptable salt is being made
It is standby to prevent and/or treat the application in diabetes medicament.The prevention and/or the treatment preferred alpha-glucosidase of diabetes medicament
Inhibitor.
Another embodiment of the present invention provides a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition is with above-mentioned
Chromone derivatives or its pharmaceutically acceptable salt are as effective component.The pharmaceutical composition may also include other α-Portugals
Polyglycoside enzyme inhibitor.The pharmaceutical composition may also include the auxiliary material (such as carrier, diluent or excipient) that can pharmaceutically connect.
The preferred solid pharmaceutical preparation of the dosage form of the pharmaceutical composition, semisolid preparation or liquid preparation.
Specific embodiment
For the ease of a further understanding of the present invention, examples provided below has done more detailed description to it.But
It is that these embodiments are only not supposed to be a limitation to the present invention or implementation principle for better understanding invention, reality of the invention
The mode of applying is not limited to the following contents.
Embodiment 1
It takes 2- hydroxyl -6- methyl benzoic acid (1.0mmol), propargyl alcohol (1.0mmol) to be dissolved in acetonitrile (3.0ml), is added
After trifluoro-methane sulfonic acid silver (AgOTf, 1.0mmol), it is heated to reflux temperature, after reaction 10 hours, after being cooled to room temperature, decompression
Concentration obtains benzopyrene through silica gel column chromatography (silica gel 200-300 mesh, eluant, eluent are petrol ether/ethyl acetate=10/1-6/1)
Muttering, (81.3%) light red solid, 155mg, yield are about to ketone derivatives；Its structure is determined through NMR and MS data:
1H NMR(acetone-d6,400MHz)δH 6.62-6.54(3H,m,Ph-H),6.14(1H,s,H-3),4.45
(2H,s,H-9),2.70(3H,s,CH3)；13C NMR(acetone-d6,100MHz)δC 178.4(C-4),166.3(C-2),
159.4(C,C-8a),142.4(C,C-5),118.4(C-7),116.4(C-6),115.6(C-4a),108.5(C-3),100.7
(C-8),60.1(C-9),22.0(C-10).ESIMS m/z 191.07[M+H]+,213.05[M+Na]+.
Embodiment 2
It takes 2- hydroxyl -6- methyl benzoic acid (1.0mmol), propargyl alcohol (1.5mmol) to be dissolved in acetonitrile (5.0ml), is added
After trifluoro-methane sulfonic acid silver (AgOTf, 0.8mmol), it is heated to reflux temperature, after reaction 8 hours, after being cooled to room temperature, decompression
Concentration obtains benzopyrene through silica gel column chromatography (silica gel 200-300 mesh, eluant, eluent are petrol ether/ethyl acetate=10/1-6/1)
Muttering, (83.6%) light red solid, 159mg, yield are about to ketone derivatives；Structural identification data and embodiment 1 are consistent.
The test of the external alpha-glucosaccharase enzyme inhibition activity of embodiment 3
Use alpha-glucosaccharase enzyme inhibition activity outside conventional PNPG method test body.
0.1mol/L phosphate buffer (pH7.2) the diluted sample and 20 μ L of 70 μ L are added into 96 orifice plates
0.5U/mL alpha-glucosidase is miscible to be placed on 37 DEG C of warm bath 30min.The PNPG of the 10mmol/L of 20 μ L is added later (to nitre
Base cresols heteroside), 37 DEG C of incubation 45min.After the 0.2mol/L Na of 80 μ L is added2CO3Solution terminates reaction, with Ah card
Wave sugar is set as positive control and detects light absorption value under microplate reader 405nm.Every group is repeated 3 times, and concurrently sets the sample under same system
Product ground control group, blank control group, A are experimental group absorbance；A0For background group absorbance；B is negative control absorbance；B0
For blank control group absorbance.Enzyme activity inhibiting rate calculation formula is as follows: inhibiting rate (%)=[(B-B0)-(A-A0)]/(B-B0)×
100%.Compound is calculated by formula to the inhibiting rate of alpha-glucosidase, and calculate its IC with Origin7.0 software50。
The IC of active testing chromone derivatives of the present invention as the result is shown50Value be 9.6 μ g/mL (acarbose
IC50Value is 2.3 μ g/mL)；Show that chromone derivatives of the present invention can be used as alpha-glucosidase restrainer, for treating,
Prevent diabetes.
Claims (10)
1. a kind of preparation process for preparing chromone derivatives, it is characterised in that include the following steps:
2- hydroxyl -6- methyl benzoic acid, propargyl alcohol are dissolved in acetonitrile, after trifluoro-methane sulfonic acid silver (AgOTf) is added, are heated to
Chromone derivatives can be obtained in 8-10 hours in reflux temperature, reaction；The structure of the chromone derivatives are as follows:
2. preparation process described in claim 1, it is characterised in that the molar ratio of 2- hydroxyl -6- methyl benzoic acid and propargyl alcohol is excellent
Select 1:1-1:1.5.
3. the described in any item preparation processes of claim 1-2, it is characterised in that the dosage of AgOTf is 2- hydroxyl -6- methylbenzene
0.8-1.0 times of formic acid mole.
4. a kind of chromone derivatives or its pharmaceutically acceptable salt, it is characterised in that the chromone derivatives
Structure are as follows:
5. chromone derivatives as claimed in claim 4 or its pharmaceutically acceptable salt are in preparation prevention and/or treatment
Application in diabetes medicament.
6. application described in claim 5, it is characterised in that the prevention and/or the treatment preferred alpha-glucosaccharase of diabetes medicament
Enzyme inhibitor.
7. a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition is derivative with benzopyrone as claimed in claim 4
Object or its pharmaceutically acceptable salt are as effective component.
8. pharmaceutical composition as claimed in claim 7, it is characterised in that the pharmaceutical composition may also include other alpha-glucosaccharases
Enzyme inhibitor.
9. the described in any item pharmaceutical compositions of claim 7-8, it is characterised in that the pharmaceutical composition may also include pharmaceutically
The auxiliary material (such as carrier, diluent or excipient) that can be connect.
10. the described in any item pharmaceutical compositions of claim 7-9, it is characterised in that the preferred solid of the dosage form of the pharmaceutical composition
Preparation, semisolid preparation or liquid preparation.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910443775.9A CN110172052A (en) | 2019-05-25 | 2019-05-25 | A kind of preparation process and application of chromone derivatives |
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| CN201910443775.9A CN110172052A (en) | 2019-05-25 | 2019-05-25 | A kind of preparation process and application of chromone derivatives |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996020186A1 (en) * | 1994-12-28 | 1996-07-04 | Dainippon Pharmaceutical Co., Ltd. | Carboxylic acid derivatives, process for producing the same, and medicinal composition containing the same |
| CN101041652A (en) * | 2007-04-25 | 2007-09-26 | 上海大学 | Separating purified new bisflavone compound from dragon's blood and preparation method thereof |
| CN101664404A (en) * | 2009-09-11 | 2010-03-10 | 吉林省中医药科学院 | Fragrant solomonseal rhizome isoflavanone extract as well as preparation method and application thereof |
-
2019
- 2019-05-25 CN CN201910443775.9A patent/CN110172052A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996020186A1 (en) * | 1994-12-28 | 1996-07-04 | Dainippon Pharmaceutical Co., Ltd. | Carboxylic acid derivatives, process for producing the same, and medicinal composition containing the same |
| CN101041652A (en) * | 2007-04-25 | 2007-09-26 | 上海大学 | Separating purified new bisflavone compound from dragon's blood and preparation method thereof |
| CN101664404A (en) * | 2009-09-11 | 2010-03-10 | 吉林省中医药科学院 | Fragrant solomonseal rhizome isoflavanone extract as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| IBRAHIM, MA 等: "α-Glucosidase and α-Amylase Inhibitory Compounds from three African Medicinal Plants: An Enzyme Inhibition Kinetics Approach", 《NATURAL PRODUCT COMMUNICATIONS》 * |
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