CN107043345B - 4-acetylbiphenyl hydrazone-indoline -2,3- diketone Schiff base preparation, structure and purposes - Google Patents
4-acetylbiphenyl hydrazone-indoline -2,3- diketone Schiff base preparation, structure and purposes Download PDFInfo
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- CN107043345B CN107043345B CN201710468260.5A CN201710468260A CN107043345B CN 107043345 B CN107043345 B CN 107043345B CN 201710468260 A CN201710468260 A CN 201710468260A CN 107043345 B CN107043345 B CN 107043345B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to structure, preparation method and some properties of a kind of Schiff base compound.The compound appearance be in yellow powdery solid, 235.8-236.3 DEG C of fusing point, molecular formula C22H17N3O, chemical name are as follows: (E) -3- ((E)-(1- (biphenyl -4- base) ethylidene)-hydrazine fork) indole-2-ketone, structure are as follows:The compounds process for production thereof is simple, to A549 lung carcinoma cell, 4T1The IC50 (half-inhibitory concentration of drug) of breast cancer cell and CT-26 colon cancer cell is respectively 40.5 μM, 47.0 μM and 38.5 μM, this shows that the compound has certain inhibitory effect to these three cancer cells.
Description
Technical field:
The present invention relates to organic syntheses and field of medicinal chemistry, have used better simply raw material and method one-step synthesis target
Product.
Background technique:
Schiff base is a kind of compound that structure is more special, can be synthesized according to the difference for introducing group different types of
Schiff base.Schiff base has important application in medicine, catalysis, analytical chemistry, corrosion and the fields such as photochromic.For example,
Medical domain, Schiff base have antibacterial, sterilization, antitumor, antiviral bioactivity；In optical material field, due to its richness
The characteristics of electronics and rigid plane, makes it have good fluorescence property and nonlinear optical property.
Report of the 4-acetylbiphenyl hydrazone class Schiff base for drug is less, but the drug molecule of the ring structure containing biphenyl is very normal
See；In drug design field, the cyclohexyl biphenyl stable system fragrant hydrophobic interaction of drug molecule, therefore it is commonly used for drug
The building of molecule.
Summary of the invention
The contents of the present invention are to have synthesized a kind of 4-acetylbiphenyl hydrazone-indoline -2,3- diketone Schiff base compound, the chemical combination
Beyond the region of objective existence see be in yellow powdery solid, 235.8-236.3 DEG C of fusing point, molecular formula C22H17N3O, chemical name are as follows: (E) -3- ((E) -
(1- (biphenyl -4- base) ethylidene)-hydrazine fork) indole-2-ketone, [english system name are as follows: (E) -3- ((E)-(1-
(biphenyl-4-yl) ethylidene) hydrazono) indolin-2-one], it is abbreviated as 3-BEHIO；Structure is as follows.
1, Structural Identification.
Elemental analysis shows that the percentage composition of its C, H, N are respectively 77.91%, 5.11% and 12.42% (based on molecule
Formula C22H17N3The theoretical value of O is respectively 77.86%, 5.05% and 12.38%), related1HNMR spectrum is shown in attached drawing 1.
2, synthetic method.
It is characterized in that in the compound synthesis method: with 4-acetylbiphenyl hydrazone and indoline -2,3- diketone for raw material, using
Solution synthesis or solid-phase synthesis.Steps are as follows:
1) 4-acetylbiphenyl hydrazone and indoline -2,3- diketone are dissolved in respectively in suitable organic solvent, are then pressed centainly
Molar ratio mixing, is stirred to react certain time at a certain temperature；It can also not have to organic solvent, directly mix two kinds of reactions
Object, griding reaction.
2) when liquid phase reactor, obtained solution is removed into most of solvent using certain method, yellow powder can be obtained
Shape solid, as target product；When solid phase reaction, grinding certain time can obtain target product.
3) target product can recrystallize in suitable organic solvent with purified product.
Preferably, above-mentioned reaction dissolvent or recrystallization are selected from organic solvent: methanol, ethyl acetate, methylene chloride, second
Alcohol, acetonitrile, acetone, chloroform, tetrahydrofuran.
Preferably, the reaction molar ratio of 4-acetylbiphenyl hydrazone and indoline -2,3- diketone is 1:4 to 4:1.
Preferably, the reaction temperature is room temperature to being heated to reflux.
Preferably, the reaction time are as follows: 0.5-12 hours.
Preferably, the method for removing solvent is nature volatilization or often/vacuum distillation.
The beneficial effects of the present invention are: function that can be more complicated with fairly simple step and reactant one-step synthesis
Molecular material, and separation method is simple.
3, anti tumor activity in vitro:
By the A549 lung carcinoma cell in logarithmic phase growth, 4T1Breast cancer cell and CT-26 colon cancer cell, are used respectively
0.25% trypsin digestion cell, become it is unicellular, with containing 10% fetal calf serum F12K culture solution be made concentration be 1.25
×107The single cell suspension of a/L, by cell inoculation in 96 well culture plates, (the every hole 2.5 × 10 every 200 μ L of hole3A cell).
96 porocyte culture plates are placed in CO2In incubator, at 37 DEG C, 5%CO2Under the conditions of, cultivate 48h.
When inner cell covers with (90% is full) when hole, this Schiff base solution (200 of various dose is added by experimental group
The hole μ L/), making the final concentration of untested compound is respectively 5 μM, 10 μM, 30 μM, 50 μM, 100 μM, and every group sets 3 multiple holes, culture
96h。
It is separately added into the MTT that 20 μ L concentration are 0.5g/L in each hole, continues to cultivate 4h, MTT is made to be reduced to first a ceremonial jade-ladle, used in libation
(Formazan).After whole supernatants are sucked out, the DMSO of 200 μ L is added in every hole, is shaked 15min, is made first a ceremonial jade-ladle, used in libation after completely dissolution, is transported
With the absorbance (OD value) at enzyme-linked immunosorbent assay instrument measurement 490nm.Then it is calculated according to the following formula:
Cell inhibitory rate %=(control group OD value-experimental group OD value)/control group OD value × 100%
Test result shows the Schiff base to A549 lung carcinoma cell, 4T1Breast cancer cell and CT-26 colon cancer cell
IC50 (half-inhibitory concentration of drug) is respectively 40.5 μM, 47.0 μM and 38.5 μM, this shows the compound to these three cancers
Cell has certain inhibitory effect.
Specific embodiment
Content in order to better understand the present invention further illustrates technology of the invention below by two specific embodiments
Scheme:
Embodiment 1.
It weighs 4-acetylbiphenyl hydrazone 0.20g (0.95mmol) to be dissolved in 30mL anhydrous methanol, heating stirring adds to whole dissolutions
Enter indoline -2,3- diketone 0.14g (0.95mmol), is heated to reflux stirring 6 hours, filtrate is then obtained by filtration, is placed in beaker
Middle standing volatilization, can obtain largely powdered precipitating, will obtain head product (yield is about 79%) after gained precipitating filtering, this head product
Ethyl alcohol recrystallization can be used, yellow powdery solid, as 3-BEHIO Schiff base are obtained.
Embodiment 2.
It weighs 4-acetylbiphenyl hydrazone 0.40g (1.9mmol) to be put into mortar, indoline -2,3- diketone 0.28g is added
(1.9mmol) grinds 3 hours, obtains target product crude product；By gained powder ethyl alcohol recrystallization, yellow powdery solid is obtained,
As 3-BEHIO Schiff base.
Detailed description of the invention
Attached drawing 1 is 4-acetylbiphenyl hydrazone-indoline -2,3- diketone Schiff base1H NMR spectra.
Claims (4)
1. a kind of compound, appearance is in yellow powdery solid, 235.8-236.3 DEG C of fusing point, molecular formula C22H17N3O, chemical name
Are as follows: (E) -3- ((E)-(1- (biphenyl -4- base) ethylidene)-hydrazine fork) indole-2-ketone, structure are as follows:
2. the preparation method of compound as described in the appended claim 1, it is characterised in that: with 4-acetylbiphenyl hydrazone and indoline -2,3-
Diketone is raw material, and using solution synthetic method, steps are as follows:
1) by 4-acetylbiphenyl hydrazone and indoline -2,3- diketone be dissolved in respectively methanol, ethyl acetate, methylene chloride, ethyl alcohol, acetonitrile,
In acetone, chloroform or tetrahydrofuran organic solvent, then mixed by 1:4 to 4:1 molar ratio, in room temperature at a temperature of being heated to reflux
It is stirred to react 0.5-12 hours；
2) obtained solution is volatilized using nature or often/vacuum distillation method removes most of solvent, yellow powder can be obtained,
As target product；
3) target product can be organic in methanol, ethyl acetate, methylene chloride, ethyl alcohol, acetonitrile, acetone, chloroform or tetrahydrofuran
Recrystallization is in solvent with purified product.
3. the preparation method of compound as described in the appended claim 1, it is characterised in that: with 4-acetylbiphenyl hydrazone and indoline -2,3-
Diketone is raw material, and using solid-phase synthesis, steps are as follows:
1) 4-acetylbiphenyl hydrazone and indoline -2,3- diketone are mixed by 1:4 to 4:1 molar ratio, at room temperature griding reaction 0.5-
12 hours, gained powder was target product head product；
2) target product head product can be in methanol, ethyl acetate, methylene chloride, ethyl alcohol, acetonitrile, acetone, chloroform or tetrahydro furan
Recrystallization mutter in organic solvent with purified product.
4. as described in the appended claim 1 compound or its pharmaceutically acceptable salt preparation prevention and/or treatment tumour medicine
Application in object, it is characterised in that: the tumour is lung cancer, breast cancer or colon cancer.
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| CN109912491B (en) * | 2019-04-08 | 2020-08-07 | 齐鲁工业大学 | Preparation and application of 4-hydroxybenzophenone hydrazone-isatin Schiff base |
| CN109824572B (en) * | 2019-04-08 | 2020-08-07 | 齐鲁工业大学 | Structure, preparation and application of 4-hydroxybenzophenone hydrazone-1-methyl-3 indole formaldehyde Schiff base |
| CN109912517B (en) * | 2019-04-08 | 2020-08-07 | 齐鲁工业大学 | Preparation and application of 4-hydroxybenzophenone hydrazone-2-acetylpyrazine Schiff base |
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|---|---|---|---|---|
| US6075044A (en) * | 1997-07-21 | 2000-06-13 | The Regents Of The University Of California | Heterocyclic derivatives as inhibitors of purine salvage phosphoribosyltransferases |
| WO2008009935A1 (en) * | 2006-07-19 | 2008-01-24 | Ucl Business Plc | Pharmaceutical compositions and their use |
| CN104193650A (en) * | 2014-08-12 | 2014-12-10 | 齐鲁工业大学 | Structure, preparation and application of benzildihydrazone-N,N'-bis(1-formacylnaphthalene) |
| CN104945302A (en) * | 2015-06-12 | 2015-09-30 | 齐鲁工业大学 | Structure, preparation and application of benzil dihydrazone-indole-3-carboxaldehyde dual-Schiff base |
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| EP1725227A1 (en) * | 2004-03-03 | 2006-11-29 | Biolipox AB | Use of new lipoxygenase inhibitors |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6075044A (en) * | 1997-07-21 | 2000-06-13 | The Regents Of The University Of California | Heterocyclic derivatives as inhibitors of purine salvage phosphoribosyltransferases |
| WO2008009935A1 (en) * | 2006-07-19 | 2008-01-24 | Ucl Business Plc | Pharmaceutical compositions and their use |
| CN104193650A (en) * | 2014-08-12 | 2014-12-10 | 齐鲁工业大学 | Structure, preparation and application of benzildihydrazone-N,N'-bis(1-formacylnaphthalene) |
| CN104945302A (en) * | 2015-06-12 | 2015-09-30 | 齐鲁工业大学 | Structure, preparation and application of benzil dihydrazone-indole-3-carboxaldehyde dual-Schiff base |
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