CN106749281A - A kind of preparation method of epinastine impurity A - Google Patents
A kind of preparation method of epinastine impurity A Download PDFInfo
- Publication number
- CN106749281A CN106749281A CN201710048200.8A CN201710048200A CN106749281A CN 106749281 A CN106749281 A CN 106749281A CN 201710048200 A CN201710048200 A CN 201710048200A CN 106749281 A CN106749281 A CN 106749281A
- Authority
- CN
- China
- Prior art keywords
- impurity
- epinastine
- preparation
- organic solvent
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to pharmaceutical technology field, there is provided a kind of preparation method of epinastine impurity A.Take appropriate hydrochloric acid epinastine and be dissolved in hydrogenperoxide steam generator, prepared by oxidation reaction and contain epinastine impurity A solution, resulting solution is isolated and purified after extracting repeatedly with column chromatography or thin-layer chromatography, and drying under reduced pressure can obtain the epinastine impurity A of higher degree.The epinastine impurity A that the present invention is prepared can as impurity reference substance, for epinastine hydrochloride about material inspection.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of 3- amino -9H- hexichol [c, f] imidazo [1,5-a] nitrogen
It is miscellaneous（Epinastine impurity A）Preparation method.
Background technology
Epinastine hydrochloride（3- amino -9,13b- dihydro -1H- hexichol [c, f] imidazo [1,5-a] azacyclonol hydrochloride salt,
Formula 1）It is histamine H1Receptor antagonist, has inhibitory action to histamine, leukotriene C, PAF, serotonin, moreover it is possible to suppress histamine,
Slow reacting substance A（SRS-A）The release of chemical mediator, can be clinically used for allergic rhinitis, nettle rash, eczema, dermatitis, skin scabies
Itch disease, pruigo, with itch psoriasis vulgaris and allergic bronchial asthma preventing and treating.Common adverse reaction had
Quick, drowsiness, gastrointestinal symptom and dysfunction of liver.
8.7 editions standards of the epinastine hydrochloride included of European Pharmacopoeia, comprising two known impurities：Impurity A（3- amino -9H- two
Benzene [c, f] imidazo [1,5-a] azepine, formula 2）And impurity B（The bromo- 9,13b- dihydros -1H- hexichol of 13b RS-3- amino -7-
[c, f] imidazo [1,5-a] azepine, formula 3）.Find that the content of impurity A can be with the time of keeping sample in epinastine stability experiment
Extend and increase, it is controllable to ensure drug quality, it is necessary to detect, control impurity A in epinastine hydrochloride bulk drug and preparation
Content, meet medicine and declare and clinical requirement.
Conventional epinastine impurity A detection method is high performance liquid chromatography, with epinastine as reference substance, by impurity A
Relative retention time（Impurity A relative retention time=impurity A retention time/epinastine retention time）Determine impurity A chromatogram
Peak position, calculates the content of impurity A.In the method, it is relative to protect because the objective factors such as instrument, chromatographic column, reagent purity influence
Stay the time not fully accurate, the positioning of impurity A is likely to occur deviation；Additionally, there is ultraviolet difference in response in impurity A and epinastine
It is different, error is there is also during assay.High performance liquid chromatography with impurity A as reference substance can directly position impurity A color
The position of spectral peak, significantly reduces or eliminates relative retention time, the influence that ultraviolet response difference brings, and Impurity A content is determined more
Directly, it is more accurate, the impurity A of high-purity is needed in the method as reference substance.
The conventional method for preparing impurity have be directly synthesized or from raw material separate method, consulting literatures data find according to
The preparation method of STING impurity A has no report, to be such as directly synthesized impurity A, then need to redesign a route for synthesis,
Construction cycle is long, high cost.If being directly separated from bulk drug and preparing impurity A, need to consume substantial amounts of bulk drug, equally
There is a problem of material high cost.Therefore, it is necessary to find a kind of easy to operate, with low cost, yield and purity is higher
The preparation method of epinastine impurity A.
The content of the invention
The invention provides a kind of preparation method of epinastine impurity A, can by aoxidizing preparation and purification procedures
Obtain the epinastine impurity A of purity more than 95%, the method preparation process is simple, low cost, high income, prepare according to
The impurity A reference substance that STING impurity A can be detected as the relevant material of epinastine hydrochloride be used.
It is comprised the following steps that：
（1）It is prepared by oxidation：Appropriate hydrochloric acid epinastine is dissolved in 10% ~ 30% hydrogenperoxide steam generator, 40 DEG C ~ 60 DEG C heating are anti-
8h ~ 28h is answered, room temperature is cooled to, the solution containing 5% ~ 10% epinastine impurity A is obtained（Can be determined with high performance liquid chromatography
Precise levels are calculated with yield）, pH value of solution is adjusted to 10 ~ 12 with alkali, add organic solvent A and extracted, collect, be associated with
Machine solvent layer, is concentrated to give mixture；
Wherein alkali is selected from NaOH, potassium hydroxide or its solution；Solvent orange 2 A is selected from dichloromethane, chloroform and ethyl acetate
In one kind.
（2）Isolate and purify：Use organic solvent B dissolving step（1）In the mixture that obtains, with organic solvent C1、C2With alkalescence
Reagent mixes as eluant, eluent or solvent by a certain percentage, is separated with column chromatography or thin-layer chromatography, collect contain according to this
The component of spit of fland impurity A, normal pressure or vacuum distillation remove solvent, are dried to obtain epinastine impurity A, and calculate receipts according to the following formula
Rate：
Wherein organic solvent B is selected from the one kind in dichloromethane, chloroform, ethyl acetate or acetone；Organic solvent C1It is selected from
One kind in dichloromethane, chloroform, ethyl acetate or acetone；Organic solvent C2Selected from methyl alcohol, ethanol, normal propyl alcohol or isopropyl
One kind in alcohol；Alkaline reagent is selected from the one kind in ammoniacal liquor, diethylamine or triethylamine；Organic solvent C in solvent1And C2Ratio
Example is 20:1~4:1, organic solvent C in eluant, eluent1And C2Ratio be 20:1~8:1；The content of alkaline reagent is 0.5% ~ 17%
（V/V）.
Method made above can further include for epinastine impurity A to be converted into pharmaceutically acceptable salt, for example, add
Enter excessive hydrochloric acid, volatilize solvent, drying can obtain epinastine impurity A hydrochloride.
In step（2）In can also collect epinastine solution, obtain epinastine after drying, salt further is obtained with hydrochloric acid
Sour epinastine, gained epinastine hydrochloride can be used for circulation and prepare epinastine impurity A and its hydrochloride.
Obtained epinastine impurity A chromatographic purity of the invention is not less than 95%, what satisfaction was used as impurity A reference substance
It is required that.Preparation process is simple, cycle is short and high income, is recycled and prepares.
Step（2）What middle column chromatography was selected is silica gel H, column chromatography silica gel self-chambering chromatographic column, can also be used commonly used in the art
Other filled columns, such as neutral alumina column, being matched by appropriate adjustment eluant, eluent can also realize similar separating effect.
The oxidation of Fig. 1 embodiments 1 prepares the high-efficient liquid phase chromatogram of resulting solution
Fig. 2 embodiments 1 isolate and purify obtained epinastine impurity A purity detecting high-efficient liquid phase chromatogram
The high-efficient liquid phase chromatogram of the relevant material detection of Fig. 3 epinastine hydrochloride tablets
Specific embodiment
Following embodiments are only used for further illustrating the present invention, are not intended to limit the present invention.
The preparation of the epinastine impurity A of embodiment 1
Epinastine hydrochloride 2g is taken, 25% hydrogenperoxide steam generator 25mL is dissolved in, 50 DEG C of heating in water bath for reaction 18h are put, after taking-up certainly
Room temperature so is cooled to, the solution containing epinastine impurity A, high performance liquid chromatography detection epinastine hydrochloride impurity A is obtained
Content（Fig. 1）；
Chromatographic condition：Chromatographic column is octadecylsilane chemically bonded silica post；Mobile phase A is acetate buffer solution（Weigh 1.61g
Ammonium chloride, 1.54g ammonium acetates, 3.84g sodium pentanesulfonates, plus 1000mL water dissolves, pH to 5.0 is adjusted with glacial acetic acid）- methyl alcohol（85:
15）, Mobile phase B is methyl alcohol；Flow velocity 0.7ml/min；Detection wavelength is 220nm；Column temperature is 40 DEG C；Gradient program is as follows：
| Time（min） | A% | B% |
| 0 | 86 | 14 |
| 3 | 86 | 14 |
| 7 | 70 | 30 |
| 15 | 30 | 70 |
| 17 | 30 | 70 |
| 17.01 | 86 | 14 |
| 20 | 86 | 14 |
Reaction solution pH to 10 is adjusted with 6N sodium hydroxide solutions, the extraction of 30ml ethyl acetate is added, ethyl acetate layer is collected, repeated
Extraction 3 times, merges the ethyl acetate solution collected, and uses Rotary Evaporators concentrate drying, obtains mixture；
Said mixture ethyl acetate is dissolved, is put and is prepared on plate in GF254 thin layer silica gel, with ethyl acetate-ethanol-ammoniacal liquor
Mixed solution is launched as solvent, wherein ethyl acetate-ethanol=4:1, the content of ammoniacal liquor（V/V）It is cumulative volume 17%,
Solvent is volatilized, blackening is observed under 254nm uviol lamps, scraping Rf values are about 0.7 blackening, are eluted with methyl alcohol, eluent room temperature
Lower nitrogen drying, drying under reduced pressure obtains orange/yellow solid 172mg, yield 86%, HPLC chromatogram purity 97%（Fig. 2）.
Excessive hydrochloric acid is added in above-mentioned orange/yellow solid, solvent is volatilized, dry epinastine impurity A hydrochloride.
HRMS：calcd for C16H13N3, 247.11793 [M+], 247.11095, found 248.11793 [M+H]+,
270.09980[M+Na]+。 1H-NMR（400Hz, CDCl3）δppm：3.60（1H, d, 12-H）4.04（1H, d, 12-H）, 6.93
（1H, s, 4-H）, 7.18 ~ 7.60（M, 8H, H-7, H-8, H-9, H-10, H-14, H-15, H-16, H-17）.13C-NMR（100Hz,
CDCl3）δppm：39.1（C-12）, 120.5（C-4）, 123.5（C-7）, 127.5（C-8）, 127.6（C-9）, 127.7（C-
10）, 127.9（C-5）, 128.0（C-14）, 128.1（C-15）, 128.7（C-16）, 129.1（C-17）, 129.4（C-13）,
133.8（C-11）, 137.1（C-18）, 138.3（C-6）, 148.3（C-2）.
The preparation of the epinastine impurity A of embodiment 2
Epinastine hydrochloride 2g is taken, 10% hydrogenperoxide steam generator 40mL is dissolved in, 60 DEG C of heating in water bath for reaction 28h are put, cooling is placed
To room temperature, the solution containing epinastine impurity A is obtained, pH to 11 is adjusted with 4N sodium hydroxide solutions, add 30ml dichloromethanes
Alkane is extracted, and collects dichloromethane layer, repeats extraction 3 times, merges the dichloromethane solution collected, and is concentrated with Rotary Evaporators, is done
It is dry to obtain mixture；
Dichloromethane dissolves said mixture, puts and is prepared on plate in GF254 thin layer silica gel, mixed with methylene chloride-methanol-triethylamine
Close solution to be launched as solvent, wherein methylene chloride-methanol=20:1, the content of triethylamine（V/V）It is cumulative volume
0.5%, solvent is volatilized, blackening is observed under 254nm uviol lamps, target impurity blackening is scraped, eluted with methyl alcohol, room temperature under nitrogen blows
Dry, drying under reduced pressure obtains orange/yellow solid 165mg, HPLC chromatogram purity 96%.
The preparation of the epinastine impurity A of embodiment 3
Epinastine hydrochloride 2g is taken, 30% hydrogenperoxide steam generator 15mL is dissolved in, 40 DEG C of heating in water bath for reaction 8h are put, cooling is placed
To room temperature, the solution containing epinastine impurity A is obtained, pH to 12 is adjusted with 4N potassium hydroxide solutions, add the chloromethanes of 30ml tri-
Alkane is extracted, and collects chloroform layer, repeats extraction 3 times, merges the chloroform soln collected, and is concentrated into Rotary Evaporators
It is dry, obtain mixture；
With acetone solution by said mixture, put and prepared on plate in GF254 thin layer silica gel, it is molten with acetone-isopropanol-ammoniacal liquor mixing
Liquid is launched as solvent, wherein acetone-isopropanol=8:1, the content of ammoniacal liquor（V/V）It is cumulative volume 10%, volatilizes solvent,
Blackening is observed under 254nm uviol lamps, target impurity blackening is scraped, is eluted with methyl alcohol, eluent room temperature under nitrogen drying, decompression is dry
It is dry to obtain orange/yellow solid 160mg, HPLC chromatogram purity 96%.
The preparation of the epinastine impurity A of embodiment 4
Epinastine hydrochloride 2g is taken, 25% hydrogenperoxide steam generator 25mL is dissolved in, 50 DEG C of heating in water bath for reaction 18h are put, after taking-up certainly
Room temperature so is cooled to, the solution containing epinastine impurity A is obtained, reaction solution pH is adjusted to 10 with 6N sodium hydroxide solutions, plus
Enter the extraction of 30ml ethyl acetate, collect ethyl acetate layer, repeat extraction 3 times, merge the ethyl acetate solution collected, steamed with rotation
Hair instrument concentrate drying, obtains mixture；
Said mixture is splined in silica gel H self-chambering chromatographic column, is entered as eluant, eluent using acetone-ethanol-ammoniacal liquor mixed solution
Row wash-out, wherein acetone-isopropanol=16:1, the content of ammoniacal liquor（V/V）It is cumulative volume 17%, it is isometric to collect column chromatography flow point,
Each flow point is detected using GF254 thin layers silica gel plate, merges purity target impurity compound flow point high, room temperature under nitrogen drying subtracts
Press dry dry orange/yellow solid 151mg, HPLC chromatogram purity 96%.
The preparation of the epinastine impurity A of embodiment 5
Epinastine hydrochloride 2g is taken, 10% hydrogenperoxide steam generator 40mL is dissolved in, 60 DEG C of heating in water bath for reaction 28h are put, cooling is placed
To room temperature, the solution containing epinastine impurity A is obtained, pH to 11 is adjusted with 4N sodium hydroxide solutions, add 30ml dichloromethanes
Alkane is extracted, and collects dichloromethane layer, repeats extraction 3 times, merges the dichloromethane solution collected, and is concentrated with Rotary Evaporators, is done
It is dry to obtain mixture；
Said mixture is splined in column chromatography silica gel self-chambering chromatographic column, is made with methylene chloride-methanol-diethylamine mixed solution
For eluant, eluent is eluted, wherein methylene chloride-methanol=20:1, the content of diethylamine（V/V）It is cumulative volume 0.5%, in equal volume
Column chromatography flow point is collected, each flow point is detected using GF254 thin layers silica gel plate, merge purity target impurity compound flow point high,
Room temperature under nitrogen is dried up, and drying under reduced pressure obtains orange/yellow solid 161mg, HPLC chromatogram purity 97%.
The preparation of the epinastine impurity A of embodiment 6
Epinastine hydrochloride 2g is taken, 30% hydrogenperoxide steam generator 15mL is dissolved in, 40 DEG C of heating in water bath for reaction 8h are put, cooling is placed
To room temperature, the solution containing epinastine impurity A is obtained, pH to 12 is adjusted with 4N potassium hydroxide solutions, add the chloromethanes of 30ml tri-
Alkane is extracted, and collects chloroform layer, repeats extraction 3 times, merges the chloroform soln collected, and is concentrated into Rotary Evaporators
It is dry, obtain mixture；
Said mixture is splined in silica gel H self-chambering chromatographic column, using acetate-methanol-ammoniacal liquor mixed solution as wash-out
Agent is eluted, wherein acetate-methanol=8:1, the content of ammoniacal liquor（V/V）It is cumulative volume 8%, it is isometric to collect column chromatography stream
Point, each flow point is detected using GF254 thin layers silica gel plate, merge purity target impurity compound flow point high, room temperature under nitrogen is dried up,
Drying under reduced pressure obtains orange/yellow solid 149mg, HPLC chromatogram purity 97%.
Impurity A content in the high effective liquid chromatography for measuring epinastine hydrochloride tablets of embodiment 7
Take test sample 10（Equivalent to epinastine hydrochloride about 200mg）, in putting 100mL measuring bottles, plus 50mL diluents（30% first
Alcohol-water）Ultrasound 5min to being disintegrated completely for shaking, plus diluent is to scale, shakes up, 10000rpm centrifugation 5min, takes supernatant and makees
It is need testing solution；It is appropriate that precision weighs epinastine impurity A reference substance, with a small amount of 0.1N dissolving with hydrochloric acid and fixed with diluent
Amount is diluted in 1ml the reference substance solution containing about 10 μ g（0.5%）；Need testing solution and each 5 μ l of reference substance solution are taken, to implement
The inspection method detection sample of impurity A in example 1.
Impurity A retention time 6.065min in epinastine hydrochloride tablets（Fig. 3）, impurity A do not do mutually with adjacent chromatographic peak
Disturb, the impurity A prepared according to this method can carry out quality control as impurity reference substance to epinastine hydrochloride tablets.
Claims (12)
1. a kind of preparation method of epinastine impurity A, comprises the following steps：
（1）It is prepared by oxidation：Take appropriate epinastine hydrochloride to be dissolved in hydrogenperoxide steam generator, room is cooled to after heating response
Temperature, obtains the solution containing epinastine impurity A, and pH value of solution to alkalescence is adjusted with alkali, adds organic solvent A, and extraction, collection have
Machine solvent layer, is concentrated to give mixture；
（2）Isolate and purify：Use organic solvent B dissolving step（1）The mixture of gained, with organic solvent C1、C2Pressed with alkaline reagent
Certain volume ratio mixes as eluant, eluent or solvent, is separated by silica gel column chromatography or silica gel thin-layer chromatography, collects
Component containing epinastine impurity A, distills, is dried to obtain epinastine impurity A.
2. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（1）Hydrogen peroxide is molten
Liquid concentration is 10% ~ 30%, and the temperature of heating is 40 DEG C ~ 60 DEG C, and the time of heating response is 8-28h.
3. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（1）Alkali be selected from hydrogen
Sodium oxide molybdena, potassium hydroxide or its solution.
4. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（1）Alkali after middle regulation
Property pH value of solution be 10 ~ 12.
5. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（1）Organic solvent
A is selected from the one kind in dichloromethane, chloroform or ethyl acetate.
6. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（2）Organic solvent
B is selected from the one kind in dichloromethane, chloroform, ethyl acetate or acetone.
7. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（2）Organic solvent
C1Selected from the one kind in dichloromethane, chloroform, ethyl acetate and acetone；Organic solvent C2Selected from methyl alcohol, ethanol, normal propyl alcohol
Or the one kind in isopropanol.
8. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（2）Middle thin-layer chromatography
The organic solvent C of solvent1、C2Ratio is 20:1~4:1.
9. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（2）Middle column chromatography is washed
The organic solvent C of de- agent1、C2Ratio is 20:1~8:1.
10. the preparation method of epinastine impurity A according to claim 1, it is characterised in that：Step（2）Alkalescence examination
Agent is selected from the one kind in ammoniacal liquor, diethylamine, triethylamine.
The preparation method of 11. epinastine impurity As according to claim 1, it is characterised in that：Step（2）Described exhibition
Open in agent or eluant, eluent, alkaline reagent content is 0.5%-17%（V/V）.
The preparation method of 12. epinastine impurity As according to claim 1, further includes to turn epinastine impurity A
Turn to pharmaceutically acceptable salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710048200.8A CN106749281A (en) | 2017-01-21 | 2017-01-21 | A kind of preparation method of epinastine impurity A |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710048200.8A CN106749281A (en) | 2017-01-21 | 2017-01-21 | A kind of preparation method of epinastine impurity A |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106749281A true CN106749281A (en) | 2017-05-31 |
Family
ID=58941492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710048200.8A Pending CN106749281A (en) | 2017-01-21 | 2017-01-21 | A kind of preparation method of epinastine impurity A |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106749281A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997349A (en) * | 2018-06-20 | 2018-12-14 | 合肥华方医药科技有限公司 | A kind of preparation method of the epinastine in relation to substance |
| CN109856279A (en) * | 2019-02-22 | 2019-06-07 | 重庆安格龙翔医药科技有限公司 | Use the method for impurity D in HPLC method analysis detection epinastine hydrochloride granule |
| CN112661762A (en) * | 2020-12-26 | 2021-04-16 | 广州艾格生物科技有限公司 | Preparation method of epinastine impurity A |
| CN113816946A (en) * | 2021-08-30 | 2021-12-21 | 杭州中美华东制药江东有限公司 | Preparation method of mupirocin impurity reference substance |
-
2017
- 2017-01-21 CN CN201710048200.8A patent/CN106749281A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997349A (en) * | 2018-06-20 | 2018-12-14 | 合肥华方医药科技有限公司 | A kind of preparation method of the epinastine in relation to substance |
| CN108997349B (en) * | 2018-06-20 | 2021-03-16 | 合肥华方医药科技有限公司 | Preparation method of epinastine related substances |
| CN109856279A (en) * | 2019-02-22 | 2019-06-07 | 重庆安格龙翔医药科技有限公司 | Use the method for impurity D in HPLC method analysis detection epinastine hydrochloride granule |
| CN112661762A (en) * | 2020-12-26 | 2021-04-16 | 广州艾格生物科技有限公司 | Preparation method of epinastine impurity A |
| CN113816946A (en) * | 2021-08-30 | 2021-12-21 | 杭州中美华东制药江东有限公司 | Preparation method of mupirocin impurity reference substance |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mustafa et al. | Synthesis, characterization, and anticoagulant activity of new functionalized biscoumarins | |
| CN106749281A (en) | A kind of preparation method of epinastine impurity A | |
| Zhu et al. | Penochalasin K, a new unusual chaetoglobosin from the mangrove endophytic fungus Penicillium chrysogenum V11 and its effective semi-synthesis | |
| CN113730391B (en) | Application of myrtle ketone compound in preparation of medicine for resisting novel coronavirus SARS-CoV-2 | |
| CN104666368B (en) | The Ganoderma total triterpenes purified and its purification process of high anti-human source activity of tumor cells | |
| CN109705188B (en) | Triterpenoid compound in exocarpium Juglandis Immaturum, and preparation method and application thereof | |
| Wang et al. | Antiviral benzofurans from Eupatorium chinense | |
| CN102584780B (en) | Glaucocalyxin derivative as well as preparing method and application thereof | |
| Valderrama et al. | Studies on quinones. Part 41: Synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones | |
| Jian et al. | Structure-cardiac activity relationship of C19-diterpenoid alkaloids | |
| JP3615240B2 (en) | Formulations containing alkaloids and antiviral agents from Mapia Hoetida | |
| CN103494806B (en) | Application of benzene a pair of horses going side by side alpha-pyrone compound and preparation method thereof | |
| Sichaem et al. | Chemical constituents from the roots of Nauclea orientalis | |
| CN102304087A (en) | Cucoline derivative as well as salts, preparation method and application thereof | |
| CN109809971B (en) | Poly-benzyl derivative, pharmaceutical composition thereof, preparation method and application thereof | |
| CN104478897A (en) | Oxazino-scutellarin aglycone derivative as well as preparation method and application thereof | |
| CN101817827A (en) | Method for preparing sesamin from sesame | |
| CN104530112B (en) | The preparation method of everolimus intermediate and its ethylization impurity | |
| CN111670191B (en) | Crystal form of pyridone derivative, preparation method and application | |
| CN102627625A (en) | Schizandrin, schisanhenol and schisandrin-b derivates and application thereof | |
| CN113387992A (en) | Obeticholic acid impurity, and preparation method and detection method thereof | |
| CN107602518B (en) | Coumarin-dithiocarbamate derivative and synthesis method thereof | |
| CN102584772A (en) | Method for preparing ochratoxin B | |
| CN101898966B (en) | Piperazine ring-containing Artemisia rupestris L. keto ester derivative as well as preparation method thereof | |
| CN111110687A (en) | Albizzia julibrissin new lignan compound for resisting lipid metabolism disorder |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170531 |