CN106349032B - Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs - Google Patents

Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs Download PDF

Info

Publication number
CN106349032B
CN106349032B CN201610722938.3A CN201610722938A CN106349032B CN 106349032 B CN106349032 B CN 106349032B CN 201610722938 A CN201610722938 A CN 201610722938A CN 106349032 B CN106349032 B CN 106349032B
Authority
CN
China
Prior art keywords
compound
eluent
ethyl acetate
ethanol
preparation
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.)
Expired - Fee Related
Application number
CN201610722938.3A
Other languages
Chinese (zh)
Other versions
CN106349032A (en
Inventor
彭成
戴鸥
熊亮
仰莲
郭力
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chengdu University of Traditional Chinese Medicine
Original Assignee
Chengdu University of Traditional Chinese Medicine
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Chengdu University of Traditional Chinese Medicine filed Critical Chengdu University of Traditional Chinese Medicine
Priority to CN201610722938.3A priority Critical patent/CN106349032B/en
Publication of CN106349032A publication Critical patent/CN106349032A/en
Application granted granted Critical
Publication of CN106349032B publication Critical patent/CN106349032B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/34—Separation; Purification; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/34—Separation; Purification; Stabilisation; Use of additives
    • C07C41/36—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses II compound represented of formula or its pharmaceutically acceptable salt, crystal form, solvates: where R1、R2Separately it is selected from hydroxyl or sulfydryl；R3、R4Separately it is selected from C1~C4The C that alkyl or halogen replace1~C4Alkyl.

Description

Bibenzyl compound, preparation method thereof and application thereof in preparing antitumor drugs
Technical Field
The invention relates to bibenzyl compounds, a preparation method thereof and application thereof in preparing antitumor drugs.
Background
The prior literature reports that bibenzyl compounds have the drug effect and the application of inhibiting passive skin allergic reaction (passive cutaneous anaphylaxis) and inhibiting β -hexosaminidase released by RBL-2H3 cells (basophilic leukemia cells) (see: Matsuda H et al. antibacterial phenyl anthranes and … Planta Med 2004; 70: 847-:
at present, no research report of the compound shown in the formula II is found, and no research report of the compound shown in the formula II used for preparing the antitumor drugs is found.
Disclosure of Invention
The invention aims to provide a new bibenzyl compound with different structures and medicinal values: a compound of formula II.
The invention provides a compound shown as a formula II or pharmaceutically acceptable salt, crystal form and solvate thereof:
wherein,
R1、R2each independently selected from hydroxy or mercapto;
R3、R4are each independently selected from C1～C4Alkyl or halogen substituted C1～C4An alkyl group.
Further, R1、R2And is simultaneously selected from hydroxyl groups.
Further, R3、R4Each independently selected from methyl, ethyl, propyl or isopropyl.
Further, the compound is
The present invention also provides a process for preparing compound C, comprising the steps of:
i. extracting rhizoma Bletillae with ethanol to obtain ethanol extractive solution;
ii. Taking the ethanol extract, and concentrating to obtain a fluid extract;
iii, dispersing the fluid extract with water, sequentially extracting with ethyl acetate and n-butanol, combining ethyl acetate parts, and recovering the solvent to obtain an ethyl acetate extract;
iv, taking the ethyl acetate extract, and performing gradient elution by adopting silica gel column chromatography by sequentially using petroleum ether-acetone as an eluent at a ratio of 100:1, 50:1 and 30:1 to obtain an eluent Fr.16 when the petroleum ether-acetone is 30: 1;
v, performing gradient elution on reverse-phase polystyrene resin columns on Fr.16 by using ethanol-water of 10:90, 30:70, 50:50, 70:30, 90:10 and 100:0 as eluent in sequence to obtain Fr.16-j when the ethanol-water of 100: 0;
vi, subjecting the Fr.16-j to a sephadex chromatographic column, and sequentially eluting by using dichloromethane-methanol (1: 1) as an eluent, wherein the eluent has the volume of 0.8 time of the column volume and 2.2 times of the column volume to obtain Fr.16-j-1 and Fr.16-j-2 respectively;
vii, subjecting fr.16-j-2 to silica gel column chromatography, eluting for 3 column volumes with dichloromethane-methanol 1:0 as eluent, and recovering the solvent to obtain fr.16-j-2 a; fr.16-j-2a by preparative thin layer chromatography with dichloromethane-acetone 20:1 as developing solvent, RfSeparation gave compound C as 0.65.
Further, in the above-mentioned case,
in the step iv, the amount of the ethyl acetate extract is 155-165 g, and the conditions of gradient elution are as follows:
in the step v, the amount of Fr.16 is 15-20 g, and gradient elution conditions are as follows:
the invention also provides application of the compound or pharmaceutically acceptable salts, crystal forms and solvates thereof in preparing medicaments for treating and/or preventing tumors.
Further, the tumor is cancer.
Further, the cancer is lung cancer.
The invention also provides a pharmaceutical composition for treating and/or preventing tumors, which is a preparation prepared by taking the compound or pharmaceutically acceptable salts, crystal forms and solvates thereof as active ingredients and adding pharmaceutically common auxiliary materials.
The novel compound shown as the formula II has good inhibition effect on tumor cells, particularly on lung cancer cells, and IC (integrated circuit) of the novel compound506.37 mu g/mL is achieved; meanwhile, the preparation method of the compound is simple and convenient, mild in reaction conditions, convenient to operate and control, low in energy consumption, high in yield, low in cost and very suitable for industrial production.
The compounds and derivatives provided in the present invention may be named according to the IUPAC (international union of pure and applied chemistry) or CAS (chemical abstracts service, Columbus, OH) naming system.
Definitions of terms used in connection with the present invention: the initial definitions provided herein for a group or term apply to that group or term throughout the specification unless otherwise indicated; for terms not specifically defined herein, the meanings that would be given to them by a person skilled in the art are to be given in light of the disclosure and the context.
"substituted" means that a hydrogen atom in a molecule is replaced by a different atom or molecule.
The minimum and maximum values of the carbon atom content in the hydrocarbon group are indicated by a prefix, e.g. prefix Ca～CbAlkyl means any alkyl group containing "a" to "b" carbon atoms. Thus, for example, C1～C4The alkyl group means an alkyl group containing 1 to 4 carbon atoms, in other words, C1～C4Alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl.
The term "pharmaceutically acceptable" means that the carrier, cargo, diluent, adjuvant, and/or salt formed is generally chemically or physically compatible with the other ingredients comprising a pharmaceutical dosage form and physiologically compatible with the recipient.
The terms "salt" and "pharmaceutically acceptable salt" refer to acid and/or base salts of the above compounds or stereoisomers thereof, with inorganic and/or organic acids and bases, as well as zwitterionic (inner) salts, and also quaternary ammonium salts, such as alkylammonium salts. These salts can be obtained directly in the final isolation and purification of the compounds. The compound or a stereoisomer thereof may be obtained by appropriately (e.g., equivalently) mixing the above compound or a stereoisomer thereof with a predetermined amount of an acid or a base. These salts may form precipitates in the solution which are collected by filtration, or they may be recovered after evaporation of the solvent, or they may be prepared by reaction in an aqueous medium followed by lyophilization. The salt in the invention can be hydrochloride, sulfate, citrate, benzene sulfonate, hydrobromide, hydrofluoride, phosphate, acetate, propionate, succinate, oxalate, malate, succinate, fumarate, maleate, tartrate or trifluoroacetate of the compound.
The mode of administration of the compounds or pharmaceutical compositions of the present invention is not particularly limited, and representative modes of administration include (but are not limited to): oral, parenteral (intravenous, intramuscular, or subcutaneous), and topical administration.
Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In these solid dosage forms, the active compound is mixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or with the following ingredients: (a) fillers or extenders, for example, starch, lactose, sucrose, glucose, mannitol and silicic acid; (b) binders, for example, hydroxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; (c) humectants, for example, glycerol; (d) disintegrating agents, for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate; (e) slow solvents, such as paraffin; (f) absorption accelerators, e.g., quaternary ammonium compounds; (g) wetting agents, such as cetyl alcohol and glycerol monostearate; (h) adsorbents, for example, kaolin; and (i) lubricants, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In capsules, tablets and pills, the dosage forms may also comprise buffering agents.
Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared using coatings and shells such as enteric coatings and other materials well known in the art. They may contain opacifying agents and the release of the active compound or compounds in such compositions may be delayed in release in a certain part of the digestive tract. Examples of embedding components which can be used are polymeric substances and wax-like substances. If desired, the active compound may also be in microencapsulated form with one or more of the above-mentioned excipients.
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or tinctures. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly employed in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, propylene glycol, 1, 3-butylene glycol, dimethylformamide and oils, in particular, cottonseed, groundnut, corn germ, olive, castor and sesame oils or mixtures of such materials and the like.
In addition to these inert diluents, the compositions can also contain adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar, or mixtures of these substances, and the like.
Compositions for parenteral injection may comprise physiologically acceptable sterile aqueous or anhydrous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols and suitable mixtures thereof.
Dosage forms for topical administration of the compounds of the present invention include ointments, powders, patches, sprays, and inhalants. The active ingredient is mixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants which may be required if necessary.
The pharmaceutically acceptable auxiliary material of the invention refers to a substance contained in a dosage form except for an active ingredient.
The pharmaceutically acceptable auxiliary components have certain physiological activity, but the addition of the components does not change the dominant position of the pharmaceutical composition in the disease treatment process, but only plays auxiliary effects, and the auxiliary effects are only the utilization of the known activity of the components and are auxiliary treatment modes which are commonly used in the field of medicine. If the auxiliary components are used together with the pharmaceutical composition of the present invention, the protection scope of the present invention still remains.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 is a HR-ESI-MS spectrum of Compound C of the present invention.
FIG. 2 is a drawing of Compound C of the present invention1H NMR spectrum.
FIG. 3 is a drawing of Compound C of the present invention13C NMR spectrum.
Detailed Description
The raw materials and equipment used in the embodiment of the present invention are known products and obtained by purchasing commercially available products.
① A Chinese medicinal composition
Bletilla striata medicinal material is purchased from Nenjiang city of Sichuan province at 8 months in 2012, and is identified as a dry tuber of Bletilla striata (Thunb.) Rchb.f. by professor Limin of Chengdu Chinese medicine university.
② reagent and filler
Column chromatography silica gel of 200-300 mesh (reagent grade) purchased from Qingdao ocean silica gel desiccant factory;
thin layer chromatography silica gel G, GF254 and H (chemically pure), purchased from Qingdao ocean silica gel desiccant factory;
MCI gel CHP 20P, 75-150 μm, is a reversed-phase polystyrene-type resin, and is purchased from Mitsubishi chemical corporation of Japan;
sephadex LH-20 sepharose, available from Amersham, Sweden;
a GF254 silica gel preparation thin layer purchased from Yangtze river friend silica gel development Co., Ltd;
chromatographic methanol, 4L/bottle, available from Fisher corporation, USA;
analytically pure reagents such as petroleum ether, ethyl acetate, n-butanol, acetone, methanol and the like are purchased from Chengdu Kelong chemical reagent factories.
③ Experimental instrument
Cometro 6000 high performance liquid chromatography (Cometro, usa);
waters Synapt G2HDMS high resolution time-of-flight mass spectrometry (Waters, usa);
nuclear magnetic resonance apparatus: bruker-600 NMR; measuring temperature: 297K; taking a solvent peak signal as a reference;
vector 22FT-IR infrared spectrometer (Bruker, Switzerland);
shimadzu UV-260 UV-visible spectrophotometer (Shimadzu, japan);
BP211D one tenth ten million electronic balance (Sartorius, switzerland);
r-210 rotary evaporator (BUCHI, Switzerland);
model DZG-6050 vacuum drying oven (shanghai semen).
Example 1 extraction and Structure identification of Compound C
(1) Extracting medicinal materials:
extracting dried rhizoma Bletillae coarse powder (3kg) with 95% ethanol under reflux for 3 times (30L × 3), each time for 2 hr;
(2) separation and purification of components:
①, concentrating the ethanol extract (90L) under reduced pressure, and drying to obtain semisolid fluid extract 510 g;
② dispersing the semisolid fluid extract (500g) with water (5L), sequentially extracting with ethyl acetate (20L) and n-butanol (20L), mixing ethyl acetate parts, and recovering solvent under reduced pressure to obtain 160g of ethyl acetate extract;
③ separating ethyl acetate extract (160g) by silica gel column chromatography, gradient eluting with petroleum ether and acetone, and detecting the eluate by thin layer chromatography to obtain eluate Fr.16 when the ratio of petroleum ether and acetone is 30: 1;
the conditions for gradient elution were as follows:
④, subjecting Fr.16 fraction (18g) to MCI treatment, gradient eluting with 10% -100% v/v ethanol water, and detecting by thin layer chromatography to obtain 10 fractions Fr.16-a-Fr.16-j;
the conditions for gradient elution were as follows:
⑤, and Fr.16-j (3.0g) passing through gel LH-20 chromatographic column, eluting with dichloromethane-methanol (1: 1) as eluent, wherein Fr.16-j-1, Fr.16-j-2, and Fr.16-j-3 are respectively the fractions collected in sequence when eluting 0.8 times of column volume, 2.2 times of column volume, and 3 times of column volume, and Fr.16-j-2 is the concentrated part of bibenzyl compound;
⑥ and Fr.16-j-2 (1.8g) by silica gel column chromatography, eluting with dichloromethane-methanol at ratio of 1:0, 200: 1, 100:1, and 50:1 respectively, eluting with 3 column volumes of eluent at each ratio, recovering solvent under reduced pressure, collecting 1:0 elution part Fr.16-j-2a to prepare thin layer colorSpectra (developing solvent dichloromethane-acetone ═ 20:1, R)f0.65) to yield compound C;
when the bibenzyl compounds in the rhizoma bletillae are developed by thin-layer chromatography, 10% sulfuric acid ethanol test solution is sprayed, and the rhizoma bletillae is developed for more than yellow, orange to reddish spots at 105 ℃ for 3min, so that the rhizoma bletillae can be used for tracking detection of bibenzyl;
compound C molecular formula C23H24O4High resolution mass spectrometry data: HR-ESI-MS M/z 363.1605[ M-H ]]-(C23H23O4Calculated as 363.1596), unsaturation 12;
nuclear magnetic resonance hydrogen spectrum of compound C (1H-NMR) and nuclear magnetic resonance carbon Spectroscopy (C13C-NMR) was measured by Bruker-AV-600 NMR, and the data are shown in Table 1;
TABLE 1 preparation of Compound C1H NMR (600MHz) and13C NMR(150MHz)in CD3COCD3data of (2)
From the above data, compound C was identified as 3' -hydroxy-4-p-hydroxybenzyl-3, 5-dimethoxybibenzyl, having the following structure:
the advantageous effects of the present invention will be specifically described below by way of test examples.
Test example 1 antitumor test
(1) Experimental materials:
① cells
Lung cancer cell a549 was derived from ATCC company, usa.
② Experimental instrument
HWCL-1 constant temperature magnetic stirring bath (Zhengzhou great wall science and trade Co., Ltd.);
BP211D one tenth ten million electronic balance (Sartorius, switzerland);
model DZG-6050 vacuum drying oven (shanghai semen);
microplate reader (Thermo 3001, Thermo Fisher Scientific);
an electronic balance (model ESJ120-4, shenyang dragon electronic weighing instrument ltd);
ultra clean bench (MCV-B161F (T), SANYO, Japan);
microscope (Primo Vert, AxioCam ERc 5s, ZEISS);
CO2incubator (HH.CP-T, Shanghai Zixin scientific instruments Co., Ltd.).
(2) The experimental method comprises the following steps:
① inoculation of cells
Cells in the logarithmic growth phase were digested with 0.25% pancreatin. The single cell suspension is prepared by culturing the cells in a cell culture medium containing 10% FBS. Counting by using a cell counting plate, inoculating A549 tumor cells in a good state to a 96-well plate to ensure that the cell density is 4 multiplied by 103Each well was filled with 100. mu.L of cell suspension, incubated at 37 ℃ with 5% CO2Culturing in an incubator for 24 h.
② drug treatment
Starting from 20. mu.g/mL of each sample, the samples were diluted with a gradient of medium, 2-fold diluted, 5 drug concentrations were set, and duplicate wells were tested for each concentration. The drug is added into each hole with the concentration of 20, 10, 5, 2.5 and 1.25 mug/mL for 100 mug L, each concentration is provided with 3 multiple holes, and the steps are repeated for 3 times. The negative control group is a culture medium solution containing a proper amount of DMSO, and the blank control group is a culture medium and a solvent which do not contain cells. The 96-well plate was returned to the incubator and exposed for 72h at 37 ℃.
③ color development and IC50Is calculated by
After 72h, 20. mu.L of MTT solution (5g/L) was added to each well in the dark, incubation was continued for 4h, the supernatant was discarded, 150. mu.L of DMSO was added to each well, the mixture was placed on a shaker and shaken at a slow speed for 10min to dissolve formazan sufficiently, and then OD at a wavelength of 570nm was measured using a microplate reader.
IC by using improved Kouya method50＝log-1[Xm-i(∑P-0.5)]A calculation was performed wherein Xm: a designed logarithm of maximum concentration; i: log of each concentration multiple concentration; e, sigma P: sum of growth inhibition rates of each group; 0.5: an empirical constant. By repeating the experiment three times, 3 ICs were calculated50Values (two decimal places are reserved), and the average value is calculated; the test results are shown in Table 2.
TABLE 2 cytotoxic Activity IC of bibenzyl Compound C of the present invention on A549 tumor cells50
NO. IC50(μg/mL)
Compound C 6.37
The results show that the bibenzyl compound has good inhibition effect on tumor cells and can be used for preparing antitumor drugs.
In conclusion, the novel compound shown in the formula II has good inhibition effect on tumor cells, particularly on lung cancer cells, and IC (integrated Circuit) of the novel compound506.37 mu g/mL is achieved; meanwhile, the preparation method of the compound is simple and convenient, mild in reaction conditions, convenient to operate and control, low in energy consumption, high in yield, low in cost and very suitable for industrial production.

Claims (7)

1. Compound C or a pharmaceutically acceptable salt thereof:
2. a process for preparing compound C, characterized in that: it comprises the following steps:
i. extracting rhizoma Bletillae with ethanol to obtain ethanol extractive solution;
ii. Taking the ethanol extract, and concentrating to obtain a fluid extract;
iii, dispersing the fluid extract with water, sequentially extracting with ethyl acetate and n-butanol, combining ethyl acetate parts, and recovering the solvent to obtain an ethyl acetate extract;
iv, taking the ethyl acetate extract, and performing gradient elution by adopting silica gel column chromatography by sequentially using petroleum ether-acetone as an eluent at a ratio of 100:1, 50:1 and 30:1 to obtain an eluent Fr.16 when the petroleum ether-acetone is 30: 1;
v, performing gradient elution on reverse-phase polystyrene resin columns on Fr.16 by using ethanol-water of 10:90, 30:70, 50:50, 70:30, 90:10 and 100:0 as eluent in sequence to obtain Fr.16-j when the ethanol-water of 100: 0;
vi, subjecting the Fr.16-j to a sephadex chromatographic column, and sequentially eluting by using dichloromethane-methanol (1: 1) as an eluent, wherein the eluent has the volume of 0.8 time of the column volume and 2.2 times of the column volume to obtain Fr.16-j-1 and Fr.16-j-2 respectively;
vii, subjecting fr.16-j-2 to silica gel column chromatography, eluting for 3 column volumes with dichloromethane-methanol 1:0 as eluent, and recovering the solvent to obtain fr.16-j-2 a; fr.16-j-2a by preparative thin layer chromatography with dichloromethane-acetone 20:1 as developing solvent, Rf(vi) 0.65, isolation to give compound C
3. The process for the preparation of compound C according to claim 2, characterized in that:
in the step iv, the amount of the ethyl acetate extract is 155-165 g, and the conditions of gradient elution are as follows:
in the step v, the amount of Fr.16 is 15-20 g, and gradient elution conditions are as follows:
4. use of a compound of claim 1 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment and/or prevention of a tumour.
5. Use according to claim 4, characterized in that: the tumor is cancer.
6. Use according to claim 5, characterized in that: the cancer is lung cancer.
7. A pharmaceutical composition for treating and/or preventing tumors, which is characterized in that: the compound or the pharmaceutically acceptable salt thereof as the active ingredient is added with pharmaceutically common auxiliary materials to prepare the preparation.
CN201610722938.3A 2016-08-24 2016-08-24 Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs Expired - Fee Related CN106349032B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610722938.3A CN106349032B (en) 2016-08-24 2016-08-24 Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610722938.3A CN106349032B (en) 2016-08-24 2016-08-24 Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs

Publications (2)

Publication Number Publication Date
CN106349032A CN106349032A (en) 2017-01-25
CN106349032B true CN106349032B (en) 2019-03-01

Family

ID=57854331

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610722938.3A Expired - Fee Related CN106349032B (en) 2016-08-24 2016-08-24 Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs

Country Status (1)

Country Link
CN (1) CN106349032B (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105001064A (en) * 2015-07-10 2015-10-28 浙江中医药大学 Bletilla striata fibrous root blestriarene A and preparation method and application thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105001064A (en) * 2015-07-10 2015-10-28 浙江中医药大学 Bletilla striata fibrous root blestriarene A and preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
中药白及中一新的联苄化合物;韩广轩 等;《药学学报》;20021231;第37卷(第3期);第194-195页
白及的化学成分及生物活性研究进展;仰莲 等;《中药与临床》;20141231;第5卷(第6期);第59-64页

Also Published As

Publication number Publication date
CN106349032A (en) 2017-01-25

Similar Documents

Publication Publication Date Title
CN110343116A (en) A kind of Flos Chrysanthemi Indici extract and preparation method thereof and the application in preparation treatment medicine for nasopharyngeal
CN115160337A (en) 1 alpha-alkyl daphnane diterpenoid compounds, and preparation method and application thereof
CN106431852B (en) Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs
CN106361731B (en) Bibenzyl compound, preparation method thereof and application thereof in preparing antitumor drugs
CN109879921B (en) Compound separated from rhizoma anemarrhenae and having antitumor activity and preparation method thereof
CN103145792B (en) Shionone type triterpene and pharmaceutical composition thereof and its preparation method and application
CN110357847B (en) Isoflavane compound and preparation method and application thereof
CN106495998B (en) A kind of bibenzyl ether compound and preparation method thereof and purposes
CN106349032B (en) Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs
CN106349031B (en) Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs
CN106397140B (en) A kind of poly bibenzyl derivative and preparation method thereof and purposes
CN111548327A (en) Carbon-reduced kaurane diterpene, preparation method thereof and application thereof in preparation of antitumor drugs
CN113633704B (en) Preparation method and application of wikstroma wikstroemia herb leaf extract
CN103183597B (en) Preparing method of diaryl neptanone compound having antineoplastic activity, and application
CN111377933B (en) Alkaloid compound extracted from orychophragmus violaceus seeds as well as extraction method and application thereof
Luo et al. Uncommon bis-amide matrine-type alkaloids from Sophora alopecuroides with anti-inflammatory effects
CN106822088B (en) Application of diene iridoid compound in preparation of anti-cancer drugs
CN109879926B (en) Triterpene glycoside compounds in Glechomae herba and extraction and separation method thereof
CN103012359B (en) (2 ' S)-Kadsuralignan J and preparation method thereof
CN109485569B (en) Acetoxy isopentene group substituted biphenyl compound and preparation method and application thereof
CN110272464B (en) Compound, preparation method thereof and application thereof in preparing antitumor drugs
CN112300185B (en) Alkaloid compound with reduced hepatotoxicity, and preparation method and application thereof
CN101412726B (en) Novel heterocyclic compounds
CN105481877B (en) A kind of new skeleton diterpene compound and preparation method and application
CN115974695B (en) Preparation method and application of vibsane diterpenoid compounds in coral tree

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20190301

Termination date: 20210824

CF01 Termination of patent right due to non-payment of annual fee