CN104693066A - Anti-hepatitis B virus active phenylpropanoids adamantine ketoxime ester compound - Google Patents
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Abstract
The invention discloses an anti-hepatitis B virus active phenylpropanoids adamantine ketoxime ester compound. The structural formula of the phenylpropanoids adamantine ketoxime ester compound is shown in the description, and by conducting a HepG2.2.15 cell experiment, we find that the compound has certain inhabitation effect on HBV surface antigen (HBsAg) and e antigen (HBeAg) and is expected to prepare anti-hepatitis B virus medicines.
Description
Technical field
The present invention relates to a series of Phenylpropanoid Glycosides adamantanone oxime ester cpds, and the synthesis of this compounds and the application in anti-hepatitis B virus activities.Specifically anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound.
Background technology
Hepatitis B (viral hepatitis type B), be called for short hepatitis B, by hepatitis B virus (Hepatitis B virus, HBV) common transmittable that causes is sick, have infectivity strong, popular wide general, route of transmission is complicated, sickness rate comparatively high.Hepatitis B is a serious global hygienic issues, can cause chronic hepatopathy and chronic infection, and the risk that patient dies from liver cirrhosis and liver cancer is very high.The whole world about 1/2 population lives is in HBV height infected zone, and about 2,000,000,000 people prove there is HBV infection, and 3-4 hundred million people is HBV chronic infection, and about 780,000 people die from acute or chronic viral hepatitis B every year, causes in the world arranging residence the 10th in the dead cause of disease.China is that the whole world infects the maximum country of hepatitis B virus number, and the infection rate of hepatitis B virus is about 60-70%, and the whole nation about 6.9 hundred million people once infected hepatitis B virus, wherein the long-term Hepatitis B carrier of 1.2 hundred million people.
The treatment of hepatitis B mainly comprises antiviral, immunomodulatory, anti-inflammatory protects the liver, anti-fibrosis etc., and wherein antiviral is crucial.At present, antiviral has two large class, Interferon, rabbit and nucleoside analogs.There is the problems such as expensive, side effect is serious in Interferon, rabbit.The focus of antiviral research since nucleoside analog is the eighties in 20th century, becomes the choice drug of current treating hepatitis B, many have lamivudine, Entecavir, adefovir ester, Telbivudine etc.But the problem of nucleoside analog ubiquity resistance and drug withdrawal knock-on, the use of nucleoside medicine simultaneously also jeopardizes the effect of hepatitis B virus vaccine.
Produce drug resistance problems in order to improve current nucleoside analogue drugs at the HBV used, some study the structural modification reported nucleoside analog, to reduce the possibility of HBV to drug resistant.Some non-nucleosides are also found like thing and are designed for and suppress HBV and help avoid resistance to produce.For this reason we design and synthesis obtain serial non-nucleoside Anti-HBV effect compound.
Summary of the invention
Object of the present invention provides a kind of anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound.
The technical scheme that the present invention solves the problems of the technologies described above is as follows
1. anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound, its general structure is as follows:
Wherein, R1, R2, R3 are H, OCH
3or-CH
2-(epidioxy propyl group).
2. the first Phenylpropanoid Glycosides adamantanone oxime ester cpds in anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound:
1) chemical name of this first Phenylpropanoid Glycosides adamantanone oxime ester cpds is: 3,4-dimethoxy-cinnamic acid-2 '-adamantanone oxime ester;
Structural formula:
Molecular formula: C
21h
25nO
4molecular weight: 355.43;
2) physico-chemical property: white crystal.Fusing point 127.6-127.8 DEG C, is dissolved in the organic solvents such as ethyl acetate, chloroform, acetone, methyl alcohol, ethanol, is insoluble in water.
Nuclear magnetic resonance data:
1h NMR (400MHz, CDCl
3): δ 1.86-2.00 (14H, m, H-diamantane), 3,89 (6H, each 3H, s, H-20,21), 6.36 (1H, d, J=15.91, H-8), 6.85 (1H, d, J=8.28, H-5), 7.05 (1H, d, J=1.79, H-2), 7.11 (1H, dd, J=1.79,8.28, H-6), 7.71 (1H, d, J=15.91, H-7).
13c NMR (100MHz, CDCl
3): δ 174.80 (C-9), 165.52 (C-10), 151.19 (C-3), 149.14 (C-4), 145.38 (C-7), 127.35 (C-1), 122.81 (C-6), 113.76 (C-8), 110.97 (C-5), 109.53 (C-2), 55.96,55.86 (C-20,21), 38.85,37.77,36.17 (C-12,14,16,17,19), 36.14,31.21,27.48 (C-11,13,15,18). mass spectrometric measurement data ESIMS:m/z 356.188 [M+H]
+, 378.344 [M+Na]
+, 735.488 [2M+H+Na]
+.
3. the second Phenylpropanoid Glycosides adamantanone oxime ester cpds in anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound:
1) chemical name of this second Phenylpropanoid Glycosides adamantanone oxime ester cpds is: 3,4,5-trimethoxy cinnamic acid-2 '-adamantanone oxime ester;
Structural formula:
Molecular formula: C
22h
27nO
5molecular weight: 385.45;
2) physico-chemical property: white crystal, fusing point: 158.6-158.9 DEG C.Be dissolved in the organic solvents such as ethyl acetate, chloroform, acetone, methyl alcohol, ethanol, be insoluble in water;
Nuclear magnetic resonance data
1h NMR (500MHz, CDCl
3): δ 1.87-2.07 (14H, m, H-diamantane), 3.89 (9H, each 3H, s, H-20,21,22), 6.42 (1H, d, J=15.92, H-8), 6.79 (2H, s, H-2,6), 7.71 (1H, d, J=15.92, H-7).
13c NMR (125MHz, CDCl
3): δ 174.96 (C-9), 165.23 (C-10), 153.41 (C-3, 5), 145.42 (C-7), 140.21 (C-4), 129.88 (C-1), 115.41 (C-8), 105.30 (C-2, 6), 60.95 (C-21), 56.15 (C-20, 22), 38.87, 37.80, 36.18 (C-12, 14, 16, 17, 19), 36.16, 31.24, 27.49 (C-11, 13, 15, 18) .DEPT135: δ 174.96, 165.23, 153.41, 140.21, 129.88 (C), 145.42, 115.41, 105.30, 36.16, 31.24, 27.49 (CH), 38.87, 37.80, 36.18 (CH
2), 60.95,56.15 (CH
3).Mass-spectrometric data ESIMS:m/z 386.3 [M+H]
+, 408.2 [M+Na]
+.
4. the third Phenylpropanoid Glycosides adamantanone oxime ester cpds in anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound:
1) chemical name of this third Phenylpropanoid Glycosides adamantanone oxime ester cpds is: 3,4-(methylene-dioxy) styracin-2 '-adamantanone oxime ester;
Structural formula:
Molecular formula: C
20h
21nO
4molecular weight: 339;
2) physico-chemical property: white crystal, fusing point 119.6-120.0 DEG C.Be dissolved in the organic solvents such as ethyl acetate, chloroform, acetone, methyl alcohol, ethanol, be insoluble in water;
Nuclear magnetic resonance data
1h NMR δ 1.82-1.99 (14H, m, H-diamantane), 6.05 (2H, s, H-20), 6.44 (1H, d, J=15.90, H-8), 6.85 (1H, d, J=7.95, H-5), 6.95 (1H, s, H-2), 6.98 (1H, d, J=7.95, H-6), 7.77 (1H, d, J=15.90, H-7).
13c NMR (100MHz, CDCl
3): δ 174.76 (C-9), 166.80 (C-10), 150.80 (C-3), 148.84 (C-4), 145.40 (C-7), 127.31 (C-1), 121.67 (C-6), 113.84 (C-8), 109.93 (C-5), 106.95 (C-2), 101.85 (C-20), 38.88, 37.48, 36.51 (C-12, 14, 16, 17, 19), 36.23, 28.78, 27.86 (C-11, 13, 15, 18) .DEPT135: δ 174.76, 166.80, 150.80, 148.84, 127.31 (C), 145.40, 121.67, 113.84, 109.93, 106.95, 36.23, 28.78, 27.86 (CH), 101.85, 38.88, 37.48, 36.51 (CH
2). mass-spectrometric data ESIMS:m/z 678.3 [2M
+], 679.0 [2M+H]
+, 701.1 [2M+Na]
+.
5. the 4th kind of Phenylpropanoid Glycosides adamantanone oxime ester cpds in anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound:
1) chemical name of the 4th kind of Phenylpropanoid Glycosides adamantanone oxime ester cpds is: 5-methoxyl group-3,4-((methylenedioxy)) styracin-2 '-adamantanone oxime ester;
Structural formula:
Molecular formula: C
21h
23nO
5molecular weight: 369.41;
2) physico-chemical property: white crystal, 159.1-159.5 DEG C.Be dissolved in the organic solvents such as ethyl acetate, chloroform, acetone, methyl alcohol, ethanol, be insoluble in water;
Nuclear magnetic resonance data
1h NMR (500MHz, CDCl
3): δ 1.89-2.06 (14H, m, H-diamantane), 3.93 (3H, s, H-21), 6.02 (2H, s, H-20), 6.35 (1H, d, J=15.84, H-8), 6.73 (1H, d, J=1.36, H-6), 6.78 (1H, d, J=1.36, H-2), 7.67 (1H, d, J=15.84, H-7).
13c NMR (125MHz, CDCl
3): δ 174.94 (C-9), 165.38 (C-10), 149.38 (C-5), 145.23 (C-7), 143.71 (C-3), 137.49 (C-4), 129.26 (C-1), 114.68 (C-8), 109.35 (C-6), 102.03 (C-20), 101.33 (C-2), 56.63 (C-21), 38.90, 37.81, 36.22 (C-12, 14, 16, 17, 19), 36.18, 31.26, 27.53 (C-11, 13, 15, 18) .DEPT135: δ 174.94, 165.38, 149.38, 143.71, 137.49, 129.26 (C), 145.23, 114.68, 109.35, 101.33, 36.18, 31.26, 27.53 (CH), 102.03, 38.90, 37.81, 36.22 (CH
2), 56.63 (CH
3). mass-spectrometric data ESIMS:m/z 370.1662 [M+H]
+, 392.1489 [M+Na]
+.
6. the preparation of Phenylpropanoid Glycosides adamantanone oxime ester compound, step is as follows:
1) will diamantane ketone, the oxammonium hydrochloride of 12mmol, the sodium acetate trihydrate of 12mmol of 10mmol be added, finally add 50ml dissolve with ethanol, stirring reaction 2 hours under 60 DEG C of conditions.After stopped reaction, solution concentrated removing ethanol, obtains enriched material.Enriched material is dissolved in 50 milliliters of methylene dichloride, and the hydrochloric acid soln 70 milliliters through 1mol/L washs three times, is separated removing upper solution, obtains lower floor's dichloromethane solution.After pickling, dichloromethane solution 70 ml waters wash three times, then separate lower floor's dichloromethane solution.Dichloromethane solution after washing finally washes 3 times with saturated sodium-chloride water solution 70 milliliters, separates lower floor and will obtain dichloromethane solution.The dichloromethane solution that obtains will be washed through 10 grams of anhydrous Na through sodium chloride solution
2sO
4drying, concentrates and obtains 2-adamantanone oxime.
2) by 3 of 10mmol, 4-dimethoxy-cinnamic acid, 3,4,5-trimethoxy cinnamic acid, 3,4-(methylene-dioxy) styracin or 5-methoxyl group-3,4-(methylene-dioxy) styracin is dissolved in 10ml methylene dichloride, adds the thionyl chloride of 50mmol, and under 65 DEG C of conditions, stirring and refluxing reacts 5 hours.Concentrate after stopped reaction and obtain 3,4-(methylene-dioxy) cinnamyl chloride, 3,4-dimethoxycinnamoyl chlorine, 3,4,5-trimethoxy cinnamyl chlorides or 5-methoxyl group-3,4-(methylene-dioxy) cinnamyl chloride.
3) by step 1) obtained 2-adamantanone oxime is dissolved in 15 milliliters of methylene dichloride, add 12mmol triethylamine and 12mmol step 2) obtained 3,4-dimethoxycinnamoyl chlorine, 3,4,5-trimethoxy cinnamyl chloride, 3,4-(methylene-dioxy) cinnamyl chlorides or 5-methoxyl group-3,4-(methylene-dioxy) cinnamyl chloride, react under 0 DEG C of condition after 30 minutes, then continue reaction 12 hours at normal temperatures.Concentrating under reduced pressure after stopped reaction, be separated by silica gel column chromatography, moving phase consists of: the sherwood oil of boiling point 60-90 DEG C: the volume ratio of ethyl acetate tapers to the solvent of 1.5:1 from 4:1, carry out gradient elution, obtain the first Phenylpropanoid Glycosides adamantanone oxime ester cpds 3, 4-dimethoxy-cinnamic acid-2 '-adamantanone oxime ester, the second Phenylpropanoid Glycosides adamantanone oxime ester cpds 3, 4, 5-trimethoxy cinnamic acid-2 '-adamantanone oxime ester, the third Phenylpropanoid Glycosides adamantanone oxime ester cpds 3, 4-((methylenedioxy)) styracin-2 '-adamantanone oxime ester and the 4th kind of Phenylpropanoid Glycosides adamantanone oxime ester cpds 5-methoxyl group-3, 4-((methylenedioxy)) styracin-2 '-adamantanone oxime ester.
7. Phenylpropanoid Glycosides adamantanone oxime ester compound is for the preparation of the medicine of hepatitis B virus resisting, the toxicity of in vitro tests Phenylpropanoid Glycosides adamantanone oxime ester compound to HepG22.2.15 cell and the suppression to HBsAg and HBeAg.Cultivating HepG22.2.15 cell DMEM substratum used is the solution containing 10% foetal calf serum, 0.03% glutamine, G418380 μ g/ml and kantlex 50 μ g/ml.Culture condition is 37 DEG C, volumetric concentration is 5%CO
2, within 2-3 days, change a nutrient solution, within 4-5 days, go down to posterity once.Phenylpropanoid Glycosides adamantanone oxime ester compound is made into mother liquor with methyl-sulphoxide respectively, 4 DEG C of preservations, faces the used time to be made into desired concn with DMEM substratum.
HepG22.2.15 cell is inoculated in the DMEM substratum in 96 orifice plates, adds Phenylpropanoid Glycosides adamantanone oxime ester compound process 9 days respectively.DMEM substratum is added after 9th day removing supernatant liquor, every hole adds 20 μ L MTT (5mg/mL), cultivate 4h again for 37 DEG C, experiment terminates, discard supernatant liquor, every hole adds 150 μ L DMSO and dissolves the MTT-first a ceremonial jade-ladle, used in libation generated in hole, by microplate reader at 490nm wavelength detecting each hole absorbance, carries out quantitatively the first a ceremonial jade-ladle, used in libation that each porocyte generates.Compare with control group (cell survival rate 100%), calculate each porocyte survival rate, to judge the cytotoxicity of medicine.
HepG22.2.15 cell is with 1 × 10
4/ mL is inoculated in the nutrient solution of 96 orifice plates, cultivates the various Phenylpropanoid Glycosides adamantanone oxime ester compound dimethyl sulfoxide solutions adding different concns after 24 hours respectively.If serum free medium group is negative control group, lamivudine group is positive controls.Experimental design is time dependent, within after adding Phenylpropanoid Glycosides adamantanone oxime ester compound every 3 days, collects supernatant liquor once, then adds the DMEM substratum containing Phenylpropanoid Glycosides adamantanone oxime ester compound, hatch 9 days altogether.The the 3rd, the 6th, the 9th day supernatant liquor collected, detects HBsAg and HBeAg in HepG22.2.15 cell conditioned medium liquid by ELISA method.
Benefit effect of the present invention:
Phenylpropanoid Glycosides adamantanone oxime ester compound provided by the present invention is Nonnucleoside anti-hepatitis B virus activities molecule, is expected to the newtype drug becoming hepatitis B virus resisting.
Phenylpropanoid Glycosides adamantanone oxime ester compound provided by the present invention all has certain restraining effect to HBsAg and HBeAg, and its inhibiting rate can reach 93.58%, and has the low feature of toxicity.
Embodiment
Below in conjunction with embodiment, the invention will be further described, but can not limit protection content of the present invention.Embodiment 1
The preparation method of the first Phenylpropanoid Glycosides oxime ester compound 3,4-dimethoxy-cinnamic acid-2 '-adamantanone oxime ester, step is as follows:
(1) will diamantane ketone, the oxammonium hydrochloride of 12mmol, the sodium acetate trihydrate of 12mmol of 10mmol be added, finally add 50ml dissolve with ethanol, stirring reaction 2 hours under 60 DEG C of conditions.After stopped reaction, solution concentrated removing ethanol, obtains enriched material.Enriched material is dissolved in 50 milliliters of methylene dichloride, and the hydrochloric acid soln 70 milliliters being 1mol/L through concentration washs three times, is separated removing upper solution, obtains lower floor's dichloromethane solution.After pickling, dichloromethane solution 70 ml waters wash three times, then separate lower floor's dichloromethane solution.Dichloromethane solution after washing finally washes 3 times with saturated sodium-chloride water solution 70 milliliters, separates lower floor and will obtain dichloromethane solution.The dichloromethane solution that obtains will be washed through 10 grams of anhydrous Na through sodium chloride solution
2sO
4drying, concentrates and obtains 2-adamantanone oxime.
(2) 3, the 4-dimethoxy-cinnamic acids of 10mmol are dissolved in 10ml methylene dichloride, add the thionyl chloride of 50mmol, under 65 DEG C of conditions, stirring and refluxing reacts 5 hours, concentrates and obtain 3,4-dimethoxycinnamoyl chlorine after stopped reaction.
(3) the 2-adamantanone oxime that embodiment step (1) is obtained is dissolved in 15 milliliters of methylene dichloride, add 12mmol triethylamine and 12mmol step (2) obtained 3, 4-dimethoxycinnamoyl chlorine, react under 0 DEG C of condition after 30 minutes, then reaction 12 hours is continued at normal temperatures, concentrating under reduced pressure after stopped reaction, be separated by silica gel column chromatography, moving phase consists of: the sherwood oil of boiling point 60-90 DEG C: the volume ratio of ethyl acetate tapers to the solvent of 1.5:1 from 4:1, carry out gradient elution, obtain the first Phenylpropanoid Glycosides adamantanone oxime ester cpds 3, 4-dimethoxy-cinnamic acid-2 '-adamantanone oxime ester.
Embodiment 2
The preparation method of the second Phenylpropanoid Glycosides oxime ester compound 3,4,5-trimethoxy cinnamic acid-2 '-adamantanone oxime ester, step is as follows:
(1) identical with the step (1) of embodiment 1.
(2) 3,4, the 5-trimethoxy cinnamic acids of 10mmol are dissolved in 10ml methylene dichloride, add the thionyl chloride of 50mmol, under 65 DEG C of conditions, stirring and refluxing reacts 5 hours, concentrates and obtain 3,4,5-trimethoxy cinnamyl chloride after stopped reaction.
(3) the 2-adamantanone oxime that step (1) is obtained is dissolved in 15 milliliters of methylene dichloride, , add the step (2) of 12mmol triethylamine and 12mmol obtained 3, 4, 5-trimethoxy cinnamyl chloride, react under 0 DEG C of condition after 30 minutes, then reaction 12 hours is continued at normal temperatures, concentrating under reduced pressure after stopped reaction, be separated by silica gel column chromatography, moving phase consists of: the sherwood oil of boiling point 60-90 DEG C: the volume ratio of ethyl acetate tapers to the solvent of 1.5:1 from 4:1, carry out gradient elution, obtain the second Phenylpropanoid Glycosides adamantanone oxime ester cpds 3, 4, 5-trimethoxy cinnamic acid-2 '-adamantanone oxime ester.
Embodiment 3
The preparation method of the third Phenylpropanoid Glycosides oxime ester compound 3,4-((methylenedioxy)) styracin-2 '-adamantanone oxime ester, step is as follows:
(1) identical with the step (1) of embodiment 1.
(2) by 3 of 10mmol, 4-(methylene-dioxy) styracin is dissolved in 10ml methylene dichloride, adds the thionyl chloride of 50mmol, and under 65 DEG C of conditions, stirring and refluxing reacts 5 hours, concentrate after stopped reaction and obtain 3,4-(methylene-dioxy) cinnyl.
(3) the 2-adamantanone oxime that step (1) is obtained is dissolved in 15 milliliters of methylene dichloride, add the step (2) of 12mmol triethylamine and 12mmol obtained 3, 4-(methylene-dioxy) cinnamyl chloride, react under 0 DEG C of condition after 30 minutes, then reaction 12 hours is continued at normal temperatures, concentrating under reduced pressure after stopped reaction, be separated by silica gel column chromatography, moving phase consists of: the sherwood oil of boiling point 60-90 DEG C: the volume ratio of ethyl acetate tapers to the solvent of 1.5:1 from 4:1, carry out gradient elution, obtain the third Phenylpropanoid Glycosides adamantanone oxime ester cpds 3, 4-((methylenedioxy)) styracin-2 '-adamantanone oxime ester.
Embodiment 4
The preparation method of the 4th kind of Phenylpropanoid Glycosides oxime ester compound 5-methoxyl group-3,4-((methylenedioxy)) styracin-2 '-adamantanone oxime ester, step is as follows:
(1) identical with the step (1) of embodiment 1.
(2) by the 5-methoxyl group-3 of 10mmol, 4-((methylenedioxy)) styracin is dissolved in 10ml methylene dichloride, add the thionyl chloride of 50mmol, under 65 DEG C of conditions, stirring and refluxing reacts 5 hours, concentrate after stopped reaction and obtain 5-methoxyl group-3,4-((methylenedioxy)) cinnamyl chloride.
(3) the 2-adamantanone oxime that step (1) is obtained is dissolved in 15 milliliters of methylene dichloride, add the 5-methoxyl group-3 that the step (2) of 12mmol triethylamine and 12mmol is obtained, 4-((methylenedioxy)) cinnamyl chloride, react under 0 DEG C of condition after 30 minutes, then reaction 12 hours is continued at normal temperatures, concentrating under reduced pressure after stopped reaction, be separated by silica gel column chromatography, moving phase consists of: the sherwood oil of boiling point 60-90 DEG C: the volume ratio of ethyl acetate tapers to the solvent of 1.5:1 from 4:1, carry out gradient elution, obtain the 4th kind of Phenylpropanoid Glycosides adamantanone oxime ester cpds 5-methoxyl group-3, 4-((methylenedioxy)) styracin-2 '-adamantanone oxime ester.
Embodiment 5
External Anti-HBV activity experiment
Phenylpropanoid Glycosides adamantanone oxime ester compound for the preparation of the medicine of hepatitis B virus resisting, the toxicity of in vitro tests Phenylpropanoid Glycosides adamantanone oxime ester compound to HepG22.2.15 cell and the suppression to HBsAg and HBeAg.Cultivating HepG22.2.15 cell DMEM substratum used is the solution containing 10% foetal calf serum, 0.03% glutamine, G418380 μ g/ml and kantlex 50 μ g/ml.Culture condition is 37 DEG C, volumetric concentration is 5%CO
2, within 2-3 days, change a nutrient solution, within 4-5 days, go down to posterity once.Phenylpropanoid Glycosides adamantanone oxime ester compound is made into mother liquor with methyl-sulphoxide respectively, 4 DEG C of preservations, faces the used time to be made into desired concn with DMEM substratum.
HepG2 2.2.15 cell is inoculated in the DMEM substratum in 96 orifice plates, adds Phenylpropanoid Glycosides adamantanone oxime ester compound process 9 days respectively.DMEM substratum is added after 9th day removing supernatant liquor, every hole adds 20 μ L MTT (5mg/mL), cultivate 4h again for 37 DEG C, experiment terminates, discard supernatant liquor, every hole adds 150 μ L DMSO and dissolves the MTT-first a ceremonial jade-ladle, used in libation generated in hole, by microplate reader at 490nm wavelength detecting each hole absorbance, carries out quantitatively the first a ceremonial jade-ladle, used in libation that each porocyte generates.Compare with control group (cell survival rate 100%), calculate each porocyte survival rate, to judge the cytotoxicity of medicine.
HepG2 2.2.15 cell is with 1 × 10
4/ mL is inoculated in the nutrient solution of 96 orifice plates, cultivates the various Phenylpropanoid Glycosides adamantanone oxime ester compound dimethyl sulfoxide solutions adding different concns after 24 hours respectively.If serum free medium group is negative control group, lamivudine group is positive controls.Experimental design is time dependent, within after adding Phenylpropanoid Glycosides adamantanone oxime ester compound every 3 days, collects supernatant liquor once, then adds the DMEM substratum containing Phenylpropanoid Glycosides adamantanone oxime ester compound, hatch 9 days altogether.The the 3rd, the 6th, the 9th day supernatant liquor collected, detects HBsAg and HBeAg in HepG22.2.15 cell conditioned medium liquid by ELISA method.
Phenylpropanoid Glycosides adamantanone oxime ester cpds all shows hypotoxicity.Table one is that Phenylpropanoid Glycosides adamantanone oxime ester cpds is to the inhibition of HBsAg.Table two is that Phenylpropanoid Glycosides adamantanone oxime ester cpds is to the inhibition of HBeAg.
Table one
Note: in table, compound number corresponds to claims compound number according to claim 2.Table two is same.
Table two
Claims (3)
1. anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound, is characterized in that, its general structure is as follows:
Wherein, R1, R2, R3 are H, OCH
3or-CH
2-(epidioxy propyl group).
2. anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester compound as claimed in claim 1, is characterized in that described anti-hepatitis B virus activities Phenylpropanoid Glycosides adamantanone oxime ester cpds has following structural formula:
1) structural formula of this first Phenylpropanoid Glycosides adamantanone oxime ester cpds:
2) structural formula of this second Phenylpropanoid Glycosides adamantanone oxime ester cpds:
3) structural formula of this third Phenylpropanoid Glycosides adamantanone oxime ester cpds:
4) structural formula of the 4th kind of Phenylpropanoid Glycosides adamantanone oxime ester cpds:
3. Phenylpropanoid Glycosides adamantanone oxime ester cpds as claimed in claim 1 is for the preparation of the medicine of hepatitis B virus resisting.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106349104A (en) * | 2016-08-24 | 2017-01-25 | 广西大学 | Oxime and oxime ether compounds with anti-hepatitis B virus activity |
| CN106718922A (en) * | 2016-12-30 | 2017-05-31 | 广西壮族自治区药用植物园 | The method for tissue culture of Momordica grosvenori high-efficiency detoxicating |
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| US4486601A (en) * | 1983-08-19 | 1984-12-04 | Pennwalt Corporation | Esters of 2-adamantanone oxime |
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| US4486601A (en) * | 1983-08-19 | 1984-12-04 | Pennwalt Corporation | Esters of 2-adamantanone oxime |
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| VASSIL ST. GEORGIEV ET AL.: "Synthesis and biological activity of 2 adamantanone oxime ester derivatives", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106349104A (en) * | 2016-08-24 | 2017-01-25 | 广西大学 | Oxime and oxime ether compounds with anti-hepatitis B virus activity |
| CN106349104B (en) * | 2016-08-24 | 2018-06-05 | 广西大学 | Oxime and oximido ether compound with anti-hepatitis B activity |
| CN106718922A (en) * | 2016-12-30 | 2017-05-31 | 广西壮族自治区药用植物园 | The method for tissue culture of Momordica grosvenori high-efficiency detoxicating |
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