CN101829079A - Application of compound of (E)-5-[6-hydroxy-5-(3-methyl-1-butenyl)-2-benzofuranyl] phenyl-1, 3-diol to preparation of pancrelipase inhibitor - Google Patents
Application of compound of (E)-5-[6-hydroxy-5-(3-methyl-1-butenyl)-2-benzofuranyl] phenyl-1, 3-diol to preparation of pancrelipase inhibitor Download PDFInfo
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- CN101829079A CN101829079A CN200910047608A CN200910047608A CN101829079A CN 101829079 A CN101829079 A CN 101829079A CN 200910047608 A CN200910047608 A CN 200910047608A CN 200910047608 A CN200910047608 A CN 200910047608A CN 101829079 A CN101829079 A CN 101829079A
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Abstract
The invention relates to the application of the compound which has the chemical formula (1), in particular to the application of the compound of (E)-5-[6-hydroxy-5-(3-methyl-1-butenyl)-2-benzofuranyl] phenyl-1, 3-diol to the preparation of pancrelipase inhibitor, belonging to the technical field of the medicament. The compound of (E)-5-[6-hydroxy-5-(3-methyl-1-butenyl)-2-benzofuranyl] phenyl-1, 3-diol is separated from the smooth-leaf artocarpus. The experiment proves that the compound of (E)-5-[6-hydroxy-5-(3-methyl-1-butenyl)-2-benzofuranyl] phenyl-1, 3-diol has strong pancrelipase inhibiting activity and can be used as the leading compound for developing and preparing the novel medicament for preventing or treating clinically-common and frequently-occurring obesity and related metabolic diseases.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of purposes of from Artocarpus nitidus Trec., separating the native compound that obtains.Be specifically related to chemical compound (E)-5-[6-hydroxyl-5-(3-methyl-1-butene base)-2-benzofuranyl] benzene-1, the purposes of 3-glycol in the preparation pancreatic lipase inhibitor.
Background technology
In nearly 20 years, the whole world especially obesity sickness rate of developed country is increasing.Because improving constantly of rapid economy development and living standard, all the time there is the relative superfluous problem of hypomotility in modern's life mode with the energy of ingesting, this has caused the absorption of numerous modern's human body energies to surpass energy expenditure, understand in the superfluous energy some as depot fat in fatty tissue, because its accumulation can be causeed fat and relevant disease, as the generation of diabetes, cancer, heart disease, hyperlipemia and fatty liver etc.
At present, the treatment of obesity mainly is to develop medicine that increases energy expenditure or the medicine that reduces caloric intake.Wherein, the main method that reduces caloric intake reduces health digestion and absorbing food product exactly, and is especially fatty.Pancreatic lipase is that fat digestion absorbs necessary enzyme in the intestinal, fat in the food is hydrolyzed to monoacylglycerol and free fatty under the pancreatic lipase effect, after intestinal is reuptaked, synthctic fat once more in vivo, cause athero, the generation of metabolic diseases such as the hyperlipemia that finally causes fat and accompany, diabetes.Pancreatic lipase inhibitor can effectively suppress in the intestinal pancreatic lipase to the decomposition catalytic action of fat, reach to reduce fat absorption and the fat purpose of treatment, thereby the effective pancreatic lipase inhibitor of development and application is subjected to people's common concern.Existing market pancreatic lipase inhibitor salable is an orlistat, and it is active strong that orlistat has, characteristics such as good stability, but have simultaneously unmanageable intestinal symptom, oil just with shortcomings such as the vomiting abdomen rises.Therefore seeking new pancreatic lipase inhibitor has great importance to the control of metabolic diseases such as obesity and diabetes.
Bibliographical information is arranged, and Trinh Phuong Lien etc. separate from Fructus Artocarpi Heterophylli platymiscium kermes and obtain structure suc as formula the compound a rtotonkin shown in (I) (Pharmazie, 1998,53 (5): 353).Do not see the bioactivity research report of this chemical compound.
Summary of the invention
The purpose of this invention is to provide the purposes of structure, be specifically related to chemical compound (E)-5-[6-hydroxyl-5-(3-methyl-1-butene base)-2-benzofuranyl as shown in the formula the chemical compound of (I)] benzene-1, the purposes of 3-glycol in the preparation pancreatic lipase inhibitor.
The chemical compound of formula of the present invention (I) structure is to extract the native compound that obtains from Artocarpus nitidus Trec.,
It has very strong inhibition activity to pancreatic lipase, can be used as the new prevention of development or the lead compound of treatment of obesity and correlated metabolism diseases medicine, also can be used for preparing prevention or treat the obesity of clinical common pilosity and the medicine of correlated metabolism diseases.
Particularly, the present invention is achieved by the following technical solutions:
After the stem branch pulverizing with Artocarpus nitidus Trec. Artocarpus nitidus Tr é c., or/and water extraction prepares total extract, used organic solvent can adopt alcohols with organic solvent, as ethanol, and methanol etc., wherein preferred 95% (volume ratio) ethanol.With total extract water-soluble after, with the extraction of petroleum ether, halogenated hydrocarbon solvent, get the halogenated hydrocarbon solvent extraction phase respectively, reclaim the solvent after drying and promptly obtain the halogenated hydrocarbon extract, used halogenated hydrocarbon solvent can be with chloroform or dichloromethane, wherein preferred chloroform.
The halogenated hydrocarbon extract is carried out silica gel column chromatography, with petroleum ether-acetone gradient elution; Wherein 4: 1 eluting of petroleum ether-acetone partly carry out silica gel column chromatography, with petroleum ether-isopropyl alcohol gradient elution; Wherein 7: 1 eluting of petroleum ether-isopropyl alcohol partly carry out PR-C
18Reversed phase column chromatography obtains chemical compound (E)-5-[6-hydroxyl-5-(3-methyl-1-butene base)-2-benzofuranyl after 65% methanol-eluted fractions] benzene-1, the 3-glycol is identified its structure with spectral method, shown in (I).
Chemical compound of the present invention (I) has carried out the pancreatic lipase active testing, the result shows, described chemical compound (I) has very strong pancreatic lipase inhibitory action, can be used as the new prevention of development or the lead compound of treatment of obesity and correlated metabolism diseases medicine, also can be used for preparing prevention or treat the obesity of clinical common pilosity and the medicine of correlated metabolism diseases.
The specific embodiment
The present invention is further elaborated below in conjunction with concrete embodiment, but do not limit the present invention.
Embodiment 1 extracts The compounds of this invention from Artocarpus nitidus Trec.
(1) extract: after 20 kilograms of powder essence of the dry stem branch of Artocarpus nitidus Trec., with percolation behind 100 liters of immersions of 95% aquiferous ethanol 12h, collect 400 liters of percolates, concentrate drying obtains 1.5 kilograms of extractum.With the water-soluble back of this extractum chloroform extraction, the recovery solvent is concentrated into dried, gets chloroform extract 50 grams.
(2) separation: chloroform extract 10 grams are carried out silica gel column chromatography,, collect stream part with petroleum ether-acetone (10: 1 → 7: 1 → 4: 1 → 2: 1) gradient elution, 1500 milliliters of each gradient consumptions; Wherein 4: 1 stream parts of petroleum ether-acetone are carried out silica gel column chromatography, with petroleum ether-isopropyl alcohol (20: 1 → 10: 1 → 7: 1 → 4: 1) gradient elution, 500 milliliters of each gradient consumptions; Wherein 7: 1 stream parts of petroleum ether-isopropyl alcohol are through PR-C
18Reversed phase column chromatography obtains chemical compound (E)-5-[6-hydroxyl-5-(3-methyl-1-butene base)-2-benzofuranyl after 65% methanol-eluted fractions] benzene-1,15 milligrams of 3-glycol (I).
The physicochemical property and the spectroscopic data of chemical compound (I) are as follows: molecular formula is C
19H
18O
4Its character is yellow amorphous powder; Electron impact mass spectra (mass-to-charge ratio): 310[M]
+Proton nmr spectra (400MHz) data (chemical shift: ppm, coupling constant: Hz, solvent: deuterated acetone): δ 8.69 (1H, s, OH-6), (8.44 2H, s, OH-12,14), 7.62 (1H, s, H-4), 7.03 (1H, br s, H-3), 7.01 (1H, br s, H-7), 6.85 (2H, d, J=1.9Hz, H-11,15), 6.77 (1H, d, J=16.0Hz, H-16), 6.37 (1H, d, J=1.9Hz, H-13), 6.21 (1H, dd, J=7.0,16.0Hz, H-17), 2.48 (1H, m, H-18), 1.10 (6H, d, J=6.7Hz, H
3-19,20); Carbon-13 nmr spectra (100MHz) data (chemical shift: ppm, solvent: deuterated acetone): 159.7 (C-12,14), 155.6 (C-2,8), 153.7 (C-6), 137.3 (C-17), 133.2 (C-9), 123.3 (C-5), 122.9 (C-16), 122.8 (C-10), 118.3 (C-4), 103.7 (C-11,15), 103.5 (C-13), 102.3 (C-3), 98.2 (C-7), 32.6 (C-18), 23.0 (C-19,20).
Embodiment 2 The compounds of this invention (I) are to the inhibition determination of activity of pancreatic lipase
At first substrate p-Nitrophenyl acetate (sigma company) is made into 1.35M with phosphate buffer (PBS, pH 7.4); Porcine pancreatic lipase (sigma company) is made into 10mg/ml with phosphate buffer; Chemical compound (I) is mixed with the solution of variable concentrations with phosphate buffer.In 96 orifice plates, add the substrate solution after 1000 times of enzymatic solution, the 40 μ l dilutions after 20 times of the 50 μ l dilutions and the given the test agent of 10 μ l variable concentrations then successively, mixing.25 ℃ were reacted 20 minutes down, detected the absorbance in every hole under 405nm every 2 minutes.
Calculating the suppression ratio (%) of given the test agent to pancreatic lipase according to the absorbance under 405nm, is contrast with the distilled water.The concentration determination that enzymatic activity suppression ratio (%) is reached 50% o'clock inhibitor is the IC50 value.Suppression ratio (%) can carry out according to following formula:
Suppression ratio (%)=[(A-B)-(C-D)]/(A-B) * 100
In the following formula, A represents to react the absorbance of back blank well under 405nm,
B represents to react the preceding absorbance of blank well under 405nm,
C represents to react the absorbance of back sample well under 405nm,
D represents to react the preceding absorbance of sample well under 405nm.
Test structure formula (I) chemical compound is to pancreatic lipase activity inhibition result, IC
50Be 3.65 ± 0.139 (μ M), show that chemical compound (I) has very strong inhibitory action to pancreatic lipase.
The fat Excessive Intake may be causeed fat and metabolism dysfunctional diseases such as diabetes relevant with obesity, hyperlipemia, fatty liver, suppresses pancreatic lipase and can suppress the decomposition of fat at small intestinal, thereby suppress fatty absorption.So as pancreatic lipase inhibitor, chemical compound (I) can be used for diseases such as prevention or treatment of obesity.
Claims (2)
1. chemical compound (E)-5-[6-hydroxyl-5-(3-methyl-1-butene the base)-2-benzofuranyl of formula (I)] benzene-1, the purposes of 3-glycol in the preparation pancreatic lipase inhibitor,
2. the purposes of the described chemical compound of claim 1 (I) in preparation prevention or treatment of obesity medicine.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009100476089A CN101829079B (en) | 2009-03-13 | 2009-03-13 | Application of compound of (E)-5-[6-hydroxy-5-(3-methyl-1-butenyl)-2-benzofuranyl] phenyl-1, 3-diol to preparation of pancrelipase inhibitor |
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| CN2009100476089A CN101829079B (en) | 2009-03-13 | 2009-03-13 | Application of compound of (E)-5-[6-hydroxy-5-(3-methyl-1-butenyl)-2-benzofuranyl] phenyl-1, 3-diol to preparation of pancrelipase inhibitor |
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| CN101829079A true CN101829079A (en) | 2010-09-15 |
| CN101829079B CN101829079B (en) | 2011-08-31 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103880797A (en) * | 2014-03-26 | 2014-06-25 | 沈阳大学 | Benzofuran compound and medical application thereof |
| CN109879840A (en) * | 2019-03-12 | 2019-06-14 | 沈阳大学 | 4- piperazine methyl -7- hydroxyl benzofuran class compound and its medical usage |
| CN115636807A (en) * | 2022-10-19 | 2023-01-24 | 南京林业大学 | Preparation method and application of two 2-aryl benzofuran derivatives |
-
2009
- 2009-03-13 CN CN2009100476089A patent/CN101829079B/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103880797A (en) * | 2014-03-26 | 2014-06-25 | 沈阳大学 | Benzofuran compound and medical application thereof |
| CN103880797B (en) * | 2014-03-26 | 2015-12-02 | 沈阳大学 | Benzofuran compounds and medicinal use thereof |
| CN109879840A (en) * | 2019-03-12 | 2019-06-14 | 沈阳大学 | 4- piperazine methyl -7- hydroxyl benzofuran class compound and its medical usage |
| CN109879840B (en) * | 2019-03-12 | 2023-04-11 | 沈阳大学 | 4-piperazinemethyl-7-hydroxybenzofuran compound and medical application thereof |
| CN115636807A (en) * | 2022-10-19 | 2023-01-24 | 南京林业大学 | Preparation method and application of two 2-aryl benzofuran derivatives |
| CN115636807B (en) * | 2022-10-19 | 2023-09-29 | 南京林业大学 | Preparation method and application of two 2-arylbenzofuran derivatives |
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| CN101829079B (en) | 2011-08-31 |
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