CN103288805A - Benzofuran-containing pyrimidine compound, its preparation method and use - Google Patents
Benzofuran-containing pyrimidine compound, its preparation method and use Download PDFInfo
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- CN103288805A CN103288805A CN2013100793032A CN201310079303A CN103288805A CN 103288805 A CN103288805 A CN 103288805A CN 2013100793032 A CN2013100793032 A CN 2013100793032A CN 201310079303 A CN201310079303 A CN 201310079303A CN 103288805 A CN103288805 A CN 103288805A
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- acceptable salt
- pharmacy acceptable
- substituted phenyl
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- FZCZSXHGFAXHLM-UHFFFAOYSA-N BrCC(NC(N=C(C1)c2cc3ccccc3[o]2)=NC1c1ccccc1)=[U] Chemical compound BrCC(NC(N=C(C1)c2cc3ccccc3[o]2)=NC1c1ccccc1)=[U] FZCZSXHGFAXHLM-UHFFFAOYSA-N 0.000 description 1
- BUVOAGPBYPJRLO-UHFFFAOYSA-N COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3C(C3OCCC3)=O)=O)N=C2c2cc(cccc3)c3[o]2)cc1 Chemical compound COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3C(C3OCCC3)=O)=O)N=C2c2cc(cccc3)c3[o]2)cc1 BUVOAGPBYPJRLO-UHFFFAOYSA-N 0.000 description 1
- DJBLTAZJTHXALQ-UHFFFAOYSA-N COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3C(c3ccc[o]3)=O)=O)N=C2c2cc(cccc3)c3[o]2)cc1 Chemical compound COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3C(c3ccc[o]3)=O)=O)N=C2c2cc(cccc3)c3[o]2)cc1 DJBLTAZJTHXALQ-UHFFFAOYSA-N 0.000 description 1
- MHGGRCMGHYUSAF-UHFFFAOYSA-N COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3C(c3ccccc3)=O)=O)N=C2c2cc(cccc3)c3[o]2)cc1 Chemical compound COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3C(c3ccccc3)=O)=O)N=C2c2cc(cccc3)c3[o]2)cc1 MHGGRCMGHYUSAF-UHFFFAOYSA-N 0.000 description 1
- YTHULWOERRFBIB-UHFFFAOYSA-N COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3c3ccccc3)=O)N=C2c2cc(cccc3)c3[o]2)cc1 Chemical compound COc1ccc(C(C2)N=C(NC(CN(CC3)CCN3c3ccccc3)=O)N=C2c2cc(cccc3)c3[o]2)cc1 YTHULWOERRFBIB-UHFFFAOYSA-N 0.000 description 1
- YAJRKRBZZZSSGF-UHFFFAOYSA-N NCCNCC(NC(N=C(C1)c2cc(cccc3)c3[o]2)=NC1c1ccccc1)=[U] Chemical compound NCCNCC(NC(N=C(C1)c2cc(cccc3)c3[o]2)=NC1c1ccccc1)=[U] YAJRKRBZZZSSGF-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a benzofuran-containing pyrimidine compound with a structure shown in formula I and its pharmaceutically acceptable salt. The invention also discloses a preparation method of the compound, and also discloses a medicinal composition with the compound or its pharmaceutically acceptable salt as the active ingredient, as well as their application as antitumor drugs, especially in preparation of drugs treating breast cancer, lung cancer, and gastric cancer.
Description
Technical field
The invention belongs to medical technical field, relate to a class and have compound of antitumor action and its production and use, or rather, what relate to that a class has an antitumor action contains pyrimidines of cumarone and its production and use.
Background technology
Human beings'health and life in the cancer serious harm.The annual people who suffers from cancer has 9,000,000 in the world according to statistics, and the patient who dies from cancer is 6,000,000, and cancer patients's death is almost just arranged p.s..The M ﹠ M of China's cancer is high, and year number of the infected is died from the number of cancer up to more than 900,000 about 1,200,000, and patient to be treated surpasses 1,500,000, and the trend that rises is year by year arranged.At present, cancer has now become the second largest killer who is only second to cardiovascular disorder.Treat cancer clinically, generally adopt operation, radiotherapy, chemotherapy three big therapies.Though embolic chemotherapy is comparatively quick, curative ratio is very low.The many cancer therapy drugs of clinical discovery exist tangible damage and toxic side effect to normal body, for example mutagenesis and genetoxic simultaneously.Therefore, seek effectively and cancer therapy drug with less body injury and toxic side effect has become the focus of new drug research.
Summary of the invention
One object of the present invention is, discloses the pyrimidines that contains cumarone and the pharmaceutical salts thereof of a class novel texture.
Another object of the present invention is, discloses a class and contains the pyrimidines of cumarone and the preparation method of pharmaceutical salts thereof.
A further object of the present invention is, open pyrimidines and the pharmaceutical salts thereof that contains cumarone with a class is the pharmaceutical composition of main active ingredient.
A further object of the invention is, discloses a class and contains the pyrimidines of cumarone and pharmaceutical salts thereof as the application of medicine for resisting malignant tumors, particularly in the purposes aspect treatment mammary cancer, lung cancer, cancer of the stomach medicine.
Now in conjunction with the object of the invention, content of the present invention is described in detail.
The present invention is specifically related to compound and the pharmacy acceptable salt thereof of formula I structure:
R
1For: hydrogen, halogen, alkyl, alkoxyl group;
R
2Be hydrogen, alkyl, phenyl, methyl substituted phenyl or halogen substituted phenyl or
R wherein
3Be phenyl, methyl substituted phenyl, halogen substituted phenyl, saturated or unsaturated quinary heterocyclic radical.
The preferred following compound of the compound of formula I structure and pharmacy acceptable salt thereof:
Wherein:
R
1For: hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxyl group;
R
2Be hydrogen, methyl, ethyl, phenyl, methyl substituted phenyl or halogen substituted phenyl or
R wherein
3Be phenyl, methyl substituted phenyl, halogen substituted phenyl, saturated or unsaturated quinary heterocyclic radical.
The compound of formula I structure is following compound and pharmacy acceptable salt thereof more preferably:
Wherein:
R
1For: hydrogen, methyl, fluorine, methoxyl group;
R
2Be hydrogen, methyl, phenyl or
R wherein
3For: phenyl, furyl, tetrahydrofuran base.
Formula I compound pharmacy acceptable salt refers to: formula I compound and mineral acid, organic acid salify.Wherein preferred: hydrochloride, hydrobromate, hydriodate, vitriol, hydrosulfate, phosphoric acid salt, acetate, propionic salt, butyrates, lactic acid salt, mesylate, tosilate, maleate, benzoate, succinate, tartrate, Citrate trianion, fumarate, taurate, gluconate, amino acid salts.
The preparation route of formula I compound is as follows:
R
1, R
2Described as defined above.
The preparation of compound (II) can reference Indian Journal of Chemistry in this preparation route, 2006,45B:1699-1703, and the general Study personnel of this research field all can conveniently make.Specific as follows:
Wherein, preferential synthetic compound (II) comprising:
Compound (II) and bromoacetyl bromide (III) are dissolved in methylene dichloride, trichloromethane, ethyl acetate, acetone, N, in dinethylformamide, tetrahydrofuran (THF), dioxane, pyridine, benzene, toluene or the acetonitrile equal solvent, under the catalysis of acid binding agents such as triethylamine, pyridine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide, potassium hydroxide or potassium tert.-butoxide ,-20～30 ℃ of reactions generate intermediate (IV).Intermediate (IV) and intermediate (V) are at methylene dichloride, trichloromethane, ethyl acetate, acetonitrile, N, in dinethylformamide, tetrahydrofuran (THF), dioxane, pyridine, acetone, benzene or the toluene, under the catalysis of acid binding agents such as triethylamine, pyridine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide, potassium hydroxide or potassium tert.-butoxide ,-20～110 ℃ of reactions generate (I).
Reaction makes all cpds or products therefrom is dissolved in dropping inorganic acid, organic acid can be made into pharmacy acceptable salt in DMF, acetone, methyl alcohol, ethanol, DMSO or the ether.
Specifically be that all cpds is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, the dripping hydrochloric acid ether is made hydrochloride to pH=2 under ice-water bath; Or all cpds is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, and adding and wait a mole taurine, heated and stirred gets its taurate; Or all cpds is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, under ice-water bath, drips the vitriol oil to pH=3, make vitriol, etc.
This compounds is effective for the treatment human malignancies.Although compound of the present invention can be without the direct administration of any preparation, described all cpds preferably uses with the form of pharmaceutical preparation, and route of administration can be non-enteron aisle approach (as vein, muscle administration) and oral administration.
The preparation of pharmaceutical compositions of The compounds of this invention is as follows: use standard and conventional technology; The compounds of this invention acceptable solid or liquid vehicle on technology of pharmaceutics are combined, and make it at random on technology of pharmaceutics acceptable auxiliary and vehicle and be combined and be prepared into particulate or microballoon.Solid dosage comprises tablet, discrete particles, capsule, slow releasing tablet, sustained release pellet etc.Solid carrier can be at least a material, and it can serve as thinner, flavouring agent, solubilizing agent, lubricant, suspension agent, tackiness agent, disintegrating agent and coating agent.Inert solid carrier comprises trimagnesium phosphate, Magnesium Stearate, smoothers sugar, lactose, pectin, propylene glycol, Polysorbate 80, dextrin, starch, gelatin, cellulose substances for example methylcellulose gum, Microcrystalline Cellulose, low melt point paraffin, polyoxyethylene glycol, N.F,USP MANNITOL, theobroma oil etc.Liquid dosage form comprises solvent, suspension for example injection, pulvis etc.
The amount of the active ingredient that contains in pharmaceutical composition and the unit dosage form (The compounds of this invention) can specifically be applied according to patient's the state of an illness, the situation of diagnosis, the amount of used compound or concentration are regulated in a wideer scope, usually, the weight range of active compound is 0.5%～90%(weight of composition).Another preferred range is 0.5%-70%.
Compound or its pharmacy acceptable salt with formula I structure of the present invention has the obvious suppression effect external to tumour.
External antitumor action:
(1) experimental technique:
Adopt classical cytotoxic activity vitro detection method mtt assay, detect the invention compound to the cell proliferation toxicity of the human tumor cells of vitro culture.
(2) experiment material:
Laboratory sample: formula I compound is provided by contriver's self-control.Sample is with the DMSO hydrotropy during experiment, and serum-free DMEM substratum is diluted to desired concn, and sample segment solution is suspension.
Main agents: MTT, the packing of Amresco company, lot number: 04M0904; Complete DMEM substratum, Gibco company product, lot number: 1290007; Calf serum, Lanzhou people's marine life, lot number: 20060509; Trypsinase, the packing of Amresco company, lot number: 016B0604; Fluorouracil Injection, 0.25g/10ml (propping up), lot number: 0512022, Tianjin gold credit amino acid company limited.
Laboratory apparatus: Bechtop, Suzhou Decontamination Equipment Plant; CO
2Incubator, Thermo company, model: HERA Cell150; Inverted microscope, Carl Zeiss company, model: Axiovert200; Enzyme-linked immunosorbent assay instrument, TECAN company, model: Sunrise; Whizzer, Kerdro company, model: Heraeus.
Cell strain: SPCA1 human lung adenocarcinoma cell line, MCF7 human breast cancer cell, SGC-7901 gastric carcinoma cells, all available from Shanghai cell research institute of the Chinese Academy of Sciences.
(3) experimental procedure:
Cell cultures: tumor cell inoculation is containing 10% calf serum, in the DMEM nutrient solution of 100IU/ml penicillin G sodium salt and 100 μ g/ml Vetstreps, places 37 ℃, 100% relative humidity, contains 5%CO
2Incubator in, it is standby after 3 times to go down to posterity.
Mtt assay is measured: the cell in the vegetative period of taking the logarithm, behind 0.25% tryptic digestion (suspension cell need not digest), be suspended in the DMEM nutrient solution that contains 10% calf serum, blow and beat into single cell suspension gently with the glass dropper, microscopically blood cell counts plate numeration viable cell.Inoculating cell suspension 90 μ L(cell concns in the every hole of 96 well culture plates are adjusted into 6～10 * 10
4Individual/ml), at 37 ℃, 100% relative humidity, contain 5%CO
2, 95% air incubator cultivate 24h after, every hole adds 10 μ L soups (final concentration is made as: 40 μ g/ml, 20 μ g/ml, 10 μ g/ml, 5 μ g/ml and five concentration of 2.5 μ g/ml).In addition, each concentration is established negative control (isoconcentration DMSO) and blank background (not adding cell), and each group is all established 6 multiple holes.Cultured continuously 24h again, every hole adds the MTT solution 10 μ L of 5mg/ml then, and after continuing to cultivate 4h, the careful suction removed supernatant liquor (suspension cell needs earlier centrifugally, inhales and removes supernatant).Every hole adds 100 μ L DMSO, puts micro oscillator concussion 5min so that crystallization is dissolved fully, and the single wavelength colorimetric of microplate reader 492nm is measured the OD value.Calculate inhibitory rate of cell growth as evaluation index with following method.
Inhibiting rate (%)=[1-(experimental group OD average-blank group OD average)/(control group OD average-blank group OD average)] * 100%.According to inhibitory rate of cell growth, calculate IC with the straight-line regression method
50Value.
(4) experimental result:
The IC of the tumour cell of table 1 pair vitro culture
50(μ g/ml)
(5) conclusion:
According to above-mentioned in vitro tests result, the compound that we have formula I structure as can be seen has stronger restraining effect to above-mentioned 3 kinds of human tumor cells.
Embodiment
The present invention is described further below in conjunction with embodiment, and embodiment only is indicative, means that never it limits the scope of the invention by any way.Described compound is through high performance liquid chromatography (HPLC), and thin-layer chromatography (TLC) detects.Can adopt subsequently such as infrared spectra (IR), nuclear magnetic resonance spectrum (
1H NMR,
13C NMR), mass spectrum (MS) etc. is further proved conclusively its structure.
Reference example 1:
The preparation of ZJ-a
The synthetic of ZJ-a carries out in the microwave synthesizer.With YL-1(16g, 0.1mol) and YL-2a(11ml, 0.1mol) put into mortar and mix, grind to form the mashed prod of homogeneous, this mashed prod is put into the microwave synthesizer, reaction 5min.Reaction in mixture impouring frozen water, is used chloroform extraction after finishing, and divides and gets organic layer, spends the night with anhydrous sodium sulfate drying.Filter, underpressure distillation obtains the brown solid crude product.Gained crude product ethyl alcohol recrystallization obtains light brown solid 20.4g, and fusing point 62.6-64.3 ℃, yield is 82.1%.Purity 96.5%(HPLC normalization method), ESI-MS (m/z): 249.1.
With reference to the method for reference example 1, can make ZJ-b, ZJ-c, ZJ-d(sees Table 2).
Table 2 compound ZJ-b-ZJ-d
Reference example 2:
The preparation of intermediate II-1
With YL-3(0.1mol, 9.6g), NaOH(0.1mol, 4g) and the ZJ-1 that makes of previous step grind homogeneous, put into the microwave synthesizer, reaction 8min finishes.In reaction mixture impouring frozen water.Filter, obtain brown solid.The solid ethyl alcohol recrystallization, obtain light brown II-1 product 18.4g, fusing point 73.8-75.1 ℃, yield is 77.5%.Purity 97.0%(HPLC normalization method), ESI-MS (m/z): 290.1.
With reference to the method for reference example 1, can make II-2, II-3, II-4(sees Table 3).
Table 3 compound I I-2-II-4:
Embodiment 1:
The preparation of compound IV-1
Be equipped with stir and three mouthfuls of reaction flasks of thermometer in, add 4g(14mmol) intermediate II-1,40ml methylene dichloride, stir and make its dissolving, adding triethylamine 2.1g(21mmol), be cooled to 0 ℃.With III(3.2g, 15mmol) be dissolved in the 10ml methylene dichloride, slowly be added drop-wise in the reaction system.Keep temperature to stir 1h, reaction finishes.In reaction solution impouring frozen water, divide and get organic layer, wash drying three times.Filter, solvent is removed in pressure distillation, obtains the brown solid crude product.Gained crude product purification by silica gel column chromatography.Finally obtain look solid 4.9g, yield 85%, purity 97.7%(HPLC normalization method), MS (m/z) [M+H]
+: 411.0.
With reference to the method for embodiment 1, get final product synthetic compound IV-2～IV-4(and see Table 4).
Table 4 compound IV-2～IV-4
Embodiment 2:
The preparation of compound I-1
Be equipped with stir and the reaction flask of thermometer in, add 1g(2.4mmol) intermediate compound IV-1,40ml acetonitrile, 0.14gNaOH (3.6mmol) drips acetonitrile (10ml) solution of 0.23g V-1 (2.6mmol), at room temperature stirs 8h, the reaction end.With reacting liquid filtering, in the filtrate impouring water, obtain the brown solid crude product.With this crude product purification by silica gel column chromatography, obtain brown product I-1, yield 74%, purity 98.8%(HPLC normalization method), MS (m/z) [M+H]
+: 416.2.
With reference to the method for embodiment 2, get final product synthetic compound I-2～I-24(and see Table 5).
Table 5 compound I-2～I-24
Embodiment 3:
Chemical compounds I-1 one-tenth hydrochloride: get chemical compounds I-1 white solid product 0.6g, be dissolved in the 8ml dehydrated alcohol.Ice-water bath is cooled to 5 ℃, drip 11.1% ethanol solution hydrochloride to pH be 2, continue at stir about 1h under the ice-water bath.Filter, vacuum-drying gets the white solid powder.
Embodiment 4:
Chemical compounds I-4 one-tenth taurate: get chemical compounds I-2 white solid product 0.5g(m.p.184.1～185.9 ℃, HPLC97.6%), be dissolved in the 10ml anhydrous methanol.Be heated to the back adding that refluxes and wait a mole taurine, continue at the about 1.5h of stirring reaction down that refluxes.Reaction finishes, and leaves standstill 24h under room temperature.Separate out light yellow crystallization, filter vacuum-drying.
Embodiment 5:
Chemical compounds I-8 one-tenth vitriol: get chemical compounds I-5 white solid product 0.3g, be dissolved in 15ml acetone.Ice-water bath is cooled to 0 ℃, drip concentrated sulfuric acid solution to pH be 3, continue at stir about 1h under the ice-water bath.Filter, get white solid.
For the pharmaceutical composition that contains the pyrimidines of cumarone of the present invention is described more fully, following FORMULATION EXAMPLE is provided below, described embodiment only is used for explanation, rather than is used for limiting the scope of the invention.Described preparation can use any active compound and the salt thereof in the The compounds of this invention, preferably uses the compound described in the embodiment 2-5.
Embodiment 6:
Prepare hard gelatin capsule with following compositions:
Consumption/capsule
Preparation technology: supplementary material is dry in advance, and it is standby to cross 100 mesh sieves.After pressing recipe quantity mentioned component being mixed, be packed in the hard gelatin capsule.
Embodiment 7:
Prepare tablet with following compositions:
Consumption/sheet
Preparation technology: supplementary material is dry in advance, and it is standby to cross 100 mesh sieves.Earlier with the abundant mixing of the auxiliary material of recipe quantity.Bulk drug is added in the auxiliary material to increase progressively dilution method, and each abundant mixing of added-time 2-3 time guarantees medicine and the abundant mixing of auxiliary material, cross 20 mesh sieves, dry 2h in 55 ℃ of ventilated drying ovens, dried particle cross the whole grain of 16 mesh sieves, measure intermediate content, mix compressing tablet on tabletting machine.
Embodiment 8:
The preparation of injection liquid:
Preparation method: get activeconstituents and join in the water for injection that dissolves polysorbate and propylene glycol, add medicinal basic adjusting pH value to 4～8 and make its dissolving.Add gac, whip attachment 30min, carbon removal, smart filter, embedding, sterilization.
Embodiment 9:
The preparation of injection lyophilized powder:
Preparation method: get activeconstituents and add water for injection, regulate the pH value with medicinal basic and make its dissolving to 4-8.Add N.F,USP MANNITOL again, carry out autoclaving by the requirement of injection, add gac, adopt filtering with microporous membrane, filtrate is carried out packing, adopts freeze-drying, makes loose block, seals, namely.
Claims (11)
1. the compound or its pharmacy acceptable salt that have formula I structure:
Wherein:
R
1For: hydrogen, halogen, alkyl, alkoxyl group;
R
2For: hydrogen, alkyl, phenyl, methyl substituted phenyl or halogen substituted phenyl,
R wherein
3Be phenyl, methyl substituted phenyl, halogen substituted phenyl, saturated or unsaturated quinary heterocyclic radical.
2. compound or its pharmacy acceptable salt with formula I structure as claimed in claim 1: wherein:
R
1For: hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxyl group;
R
2For: hydrogen, methyl, ethyl, phenyl, the methyl substituted phenyl, halogen substituted phenyl,
R wherein
3Be phenyl, methyl substituted phenyl, halogen substituted phenyl, saturated or unsaturated quinary heterocyclic radical.
3. as each described compound or its pharmacy acceptable salt with formula I structure of claim 1-2, be selected from:
4. as each described compound or its pharmacy acceptable salt with formula I structure of claim 1-3, its pharmacy acceptable salt is: formula I compound and mineral acid, organic acid salify.
5. compound or its pharmacy acceptable salt with formula I structure as claimed in claim 4; its pharmacy acceptable salt is: hydrochloride, hydrobromate, hydriodate, vitriol, hydrosulfate, phosphoric acid salt, acetate, propionic salt, butyrates, lactic acid salt, mesylate; tosilate, maleate, benzoate, succinate, tartrate, Citrate trianion, fumarate, taurate.
6. as each described preparation method with compound of formula I structure of claim 1-3, it is characterized in that: in non-protonic solvent, compound ii and compound III prepare compound IV under the acid binding agent effect, compound IV and compound V prepare formula I compound under the acid binding agent effect;
R
1, R
2Definition according to claim 1.
7. preparation method as claimed in claim 6, it is characterized in that: described non-protonic solvent is methylene dichloride, trichloromethane, ethyl acetate, acetone, N, dinethylformamide, tetrahydrofuran (THF), dioxane, pyridine, benzene, toluene or acetonitrile.
8. preparation method as claimed in claim 6, it is characterized in that: described acid binding agent is triethylamine, pyridine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide, potassium hydroxide or potassium tert.-butoxide.
9. pharmaceutical composition, it comprise the treatment significant quantity as each described compound or its pharmacy acceptable salt and one or more pharmaceutical carrier with formula I structure among the claim 1-2.
As each described compound with formula I structure or its pharmacy acceptable salt among the claim 1-3 in the application aspect antitumor drug.
11. application as claimed in claim 10 is in the purposes aspect treatment mammary cancer, lung cancer, cancer of the stomach medicine.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1440404A (en) * | 2000-07-29 | 2003-09-03 | 阿皮德公开股份有限公司 | Benzofuran derivatives and their use as antibacterial agents |
| US20090281336A1 (en) * | 2002-11-01 | 2009-11-12 | Saha Ashis K | Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis c viral infections and associated diseases |
-
2013
- 2013-03-13 CN CN201310079303.2A patent/CN103288805B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1440404A (en) * | 2000-07-29 | 2003-09-03 | 阿皮德公开股份有限公司 | Benzofuran derivatives and their use as antibacterial agents |
| US20090281336A1 (en) * | 2002-11-01 | 2009-11-12 | Saha Ashis K | Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis c viral infections and associated diseases |
Non-Patent Citations (3)
| Title |
|---|
| D B ARUNA KUMAR 等: "Microwave assisted facile synthesis of aminopyrimidines bearing benzofuran and investigation of their antimicrobial activity", 《INDIAN JOURNAL OF CHEMISTRY》 * |
| V. KANAGARAJAN 等: "Pyrimidino piperazinyl acetamides: innovative class of hybrid acetamide drugs as potent antimicrobial and antimycobacterial agents", 《PHARMACEUTICAL CHEMISTRY JOURNAL》 * |
| YADAV, D. BODKE 等: "Synthesis and biological evaluation of 3-aryl-1-(2-benzofuryl)-2-propen-1-one analogs", 《INDIAN JOURNAL OF HETEROCYCLIC CHEMISTRY》 * |
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