CN108530435A - A kind of 1,4- pentadiene -3- ketones derivants containing quinoxaline, preparation method and application - Google Patents
A kind of 1,4- pentadiene -3- ketones derivants containing quinoxaline, preparation method and application Download PDFInfo
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Abstract
3 ketones derivant of Isosorbide-5-Nitrae pentadiene that the invention discloses a kind of containing quinoxaline, preparation method and application, general formula (I) are as follows：Wherein, R1For phenyl, substituted-phenyl or substitution aromatic heterocyclic；R is more than one hydrogen atom, methoxyl group, nitro, methyl, trifluoromethyl or the halogen atom contained on 5,6,7 or 8 in quinoxaline structure.The compounds of this invention has excellent inhibitory activity to 7721 cells of liver cancer SMMC, shows higher antitumor activity, can be used as potential anti-tumor agents and uses.
Description
Technical field
The present invention relates to chemical technology field, relates in particular to a kind of Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ether ketones and spread out
Biology, also relate to the Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ketones derivants preparation method and this contain quinoxaline
Application of the 1,4- pentadiene -3- ketones derivants in terms of preparing human body liver-cancer medicine.
Background technology
Curcumin is widely used as fragrance, food preservative, taste as a kind of polyphenol compound in turmeric
Essence and dyestuff.Isosorbide-5-Nitrae-pentadiene -3- ketone compounds are as a kind of important curcumin derivate, because it is with desinsection, suppression
Bacterium, Antiphytoviral, antitumor, anti-inflammatory and the more wide spectrum biological activity such as anti-oxidant, have been increasingly becoming a kind of important doctor
Medicine elder generation conductor and be concerned by people.Recent studies indicate that 1,4- pentadiene -3- ketone compounds are removed in prevention agricultural
Outside being played an important role in terms of disease, there is important application value in field of medicaments.
(Xue Wei, Chen Yu, Chou Qiujuan, Gong Huayu, Li Haichang, the synthesis of the Tao Yang curcumin derivates of esters containing oxime such as Xue Wei
And antitumor activity [J] molecular science journals, 2013,29 (3), 198-204.) synthesize a series of asymmetry 1,5- bis-
Aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime ester compounds, after discovery is handled 72 hours in the case where drug concentration is 10 μ g/L,
Such compound on prostate cancer cell PC3 cell shows certain inhibitory activity.(Luo, the H. such as Luo；Yang,S.；Cai,
Y.；Peng,Z.；Liu,T.Synthesis and biological evaluation of novel 6-chloro-
quinazolin derivatives as potential antitumor agents[J].European Journal of
Medicinal Chemistry,2014,84:A series of 1,4- pentadiene -3- ketones containing quinazoline 746-752.) are synthesized
Compound, find drug concentration be 10 μM under conditions of processing 72h after, such compound to gastric carcinoma cells (MGC-803),
Human breast cancer cell (Bcap-37) and prostate gland cancer cell (PC3) have certain inhibitory activity.
(Liu Chunli, history, Liu Jinyan, Wei Bing, Mao Fei, Xiang Mingjie, the Li Jian .2- imidazole radicals -1,4- penta 2 such as Liu Chunli
The synthesis of alkene -3- ketones derivants and its antibacterial activity research [J] China journal of Medicinal Chemistry, 2015,25:15-23.) synthesis
A series of 2- imidazole radicals-Isosorbide-5-Nitrae-pentadiene -3- ketones derivants, find such compound to staphylococcus epidermis and golden yellow
Staphylococcus has certain inhibiting effect.(Baldwin, the P.R. such as Baldwin；Reeves,A.Z.；Powell,K.R.；
Napier,R.J.；Swimm,A.I.；Sun,A.；Giesler,K.；Bommarius,B.；Shinnick,T.M.；Snyder,
J.P.；Liotta,D.C.；Kalman,D.Monocarbonyl analogs of curcumin inhibit growth of
antibiotic sensitive and reshistant stains of Myco-bacoterium tuberculosis
[J].European Journal of Medicinal Chemistry,2015,92:693-699.) design has synthesized 8 kinds of lists
Carbonyl curcumin derivative finds that such compound has good inhibiting effect to Mycobacterium marinum.
Quinoxaline is a kind of important benzopyrazines heterocyclic compounds with armaticity.Many quinoxaline derivant tools
There are anticancer, antibacterial isoreactivity.Since quinoxaline derivant has a wide range of applications in medicine, pesticide, dyestuff etc., so its
Study on the synthesis receives much attention.Therefore, one of the resource of significant during quinoxaline is studied as new drug development from now on, has very
Big development prospect.
Invention content
It is an object of the invention to overcome disadvantages mentioned above and provide it is a kind of to SMMC-7721 liver cancer cells have it is excellent
Inhibitory activity shows higher antitumor activity, can be used as the Isosorbide-5-Nitrae-penta containing quinoxaline that potential anti-tumor agents use
Diene -3- ketones derivants.
The preparation side of another object of the present invention is to provide this 1,4- pentadiene -3- ketones derivants containing quinoxaline
Method.
Another object of the present invention is that the 1,4- pentadiene -3- ketones derivants containing quinoxaline are preparing human body liver
Application in terms of cancer drug.
A kind of Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ketones derivants of the present invention, general formula are as follows：
Wherein, R1For phenyl, substituted-phenyl or substitution aromatic heterocyclic；R is to contain on 5,6,7 or 8 in quinoxaline structure
More than one hydrogen atom, methoxyl group, nitro, methyl, trifluoromethyl or halogen atom.
A kind of preparation method of Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ketones derivants of the present invention, includes the following steps：
(1) using acetone, salicylide or 4- hydroxy benzaldehydes as raw material, 2- (hydroxy phenyl) -3- butylene-is prepared under alkaline condition
2- ketone or 4- (hydroxy phenyl)-3- butene-2 -one:
(2) using substituted aroma aldehyde, 2- (hydroxy phenyl) -3- butene-2s -one or 4- (hydroxy phenyl) -3- butene-2s -one as raw material,
1- substituted aryls -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone or 1- substituted aryls -5- (2- hydroxyls are prepared under alkaline condition
Base phenyl) -1,4- pentadiene -3- ketone：
(3) with the 2- chloro-quinoxalines of 2- hydroxy quinoxalines and the preparation of phosphorus oxychloride raw material containing substituent group containing substituent group：
(4) 1- (2- hydroxy phenyls) -5- (substituted aromatic base) -1,4- pentadiene -3- ketone and 1- (4- hydroxy phenyls) -5- (substitutions
Aromatic radical)-Isosorbide-5-Nitrae-pentadiene -3- ketone with containing substituent group 2- chloro-quinoxalines occur etherification reaction, generate the Isosorbide-5-Nitrae-containing quinoxaline
Pentadiene -3- ketones derivants：
A kind of 1,4- pentadiene -3- ketones derivants containing quinoxaline of the present invention are in terms of preparing human body liver-cancer medicine
Application.
Compared with prior art, the present invention there is apparent advantageous effect, as can be known from the above technical solutions：The present invention is with water
Poplar aldehyde and parahydroxyben-zaldehyde react aldol reaction with acetone and generate 4- (2- hydroxy phenyls) -3- butene-2s -one and 4- (4-
Hydroxy phenyl)-3- butene-2 -one, 4- (2- hydroxy phenyls)-3- butene-2s -one and 4- (4- hydroxy phenyls)-3- butene-2 -one
Aldol reaction occurs with substituted aroma formaldehyde and generates 1- (2- hydroxy phenyls) -5- (substituted aromatic base) -1,4- pentadienes -3-
Ketone and 1- (4- hydroxy phenyls) -5- (substituted aromatic base)-Isosorbide-5-Nitrae-pentadiene -3- ketone, 1- (2- hydroxy phenyls) -5- (substituted aromas
Base)-Isosorbide-5-Nitrae-pentadiene -3- ketone with containing substituent group 2- chloro-quinoxalines occur etherification reaction, generate the Isosorbide-5-Nitrae-penta two containing quinoxaline
Alkene -3- ketones derivants.There is good inhibiting effect to human hepatoma cell SMMC-7721, can be used for making antineoplastic
Agent uses.
Quinoxaline structure with excellent activity is introduced into the structure of pentadienone, has synthesized and has contained in a series of structures
The pentadiene ketone compounds of quinoxaline, and the synthesized Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ketone compounds are applied to
In terms of active anticancer, it is more prominent that experiment finds that such compound possesses with current commodity chemical drug agent compared in terms of active anticancer
The activity gone out, wherein most compound all show human hepatocellular SMMC-7721 cytosiies 72h in terms of active anticancer
Go out significant inhibition, show higher antitumor activity, can be used as anti-tumor agents use.
Specific implementation mode
Embodiment 1
(compound number is for the synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (2- thienyls) -1,4- pentadiene -3- ketone
N1), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：4- hydroxy benzaldehydes (6.1g) are added in the acetone of 60mL,
After stir about 15min, after the ice bath reaction system about 30min, 5% NaOH solution of about 100mL is added into system, waits dripping
After adding, ice bath room is removed, stirring at normal temperature is about for 24 hours.It waits for after reaction, system is transferred in the beaker of 500mL and is added
Enter appropriate ice water, after being about then 5~6 with 5% dilute hydrochloric acid solution regulation system pH, there are a large amount of yellow solids to be precipitated, will consolidate
Body is extracted out, finally ethanol/water system is used to recrystallize to get yellow solid, yield 68%.
(2) synthesis of 1- (2- thienyls) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：By 4- (hydroxy phenyl)-
3- butene-2s -one (4.0g), thiophene -2-formaldehyde (2.86mL) and 50mL ethyl alcohol are added in the three-necked flask of 250mL, stir about
After 30min, 5% NaOH solution of 60mL into system removes ice bath room, stirring at normal temperature is about for 24 hours after being added dropwise.It waits for
After reaction, system is transferred in the beaker of 500mL and appropriate ice water is added, then adjusted with 5% dilute hydrochloric acid solution
After system pH is about 5~6, there are a large amount of yellow solids to be precipitated, solid is extracted out to get yellow solid, yield 82%.
(3) synthesis of 2- chloro-quinoxalines：2- hydroxy quinoxalines (2g) and phosphorus oxychloride (20mL) are placed in three mouthfuls of 100mL
It is stirred in bottle, 5 drop DMF is added, system is transferred in the beaker of 500mL after the 2h that flows back, is added in appropriate ice water.White is precipitated
Solid, yield 75%.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (2- thienyls) -1,4- pentadiene -3- ketone：By 1- (2-
Thienyl) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone (0.53g), 2- chloro-quinoxalines (0.3g), potassium carbonate (0.47g)
With acetonitrile (30mL), it is to be mixed uniformly after be heated to reflux, after about 3~4h reaction terminate, go molten, column chromatography obtains yellow solid,
Yield 56%.
Embodiment 2
(compound number is for the synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- aminomethyl phenyls) -1,4- pentadiene -3- ketone
N2), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- aminomethyl phenyls) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment 1 (2)
Step, difference lies in using 4- tolyl aldehydes as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- aminomethyl phenyls) -1,4- pentadiene -3- ketone：As implemented
1 (4) step of example, difference lies in using 1- (4- aminomethyl phenyls) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
Embodiment 3
(compound number is for the synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (3- pyridyl groups) -1,4- pentadiene -3- ketone
N3), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (3- pyridyl groups) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment 1 (2)
Step, difference lies in using pyridine -3- formaldehyde as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (3- pyridyl groups) -1,4- pentadiene -3- ketone：Such as embodiment
1 (4) step, difference lies in using 1- (3- pyridyl groups) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
Embodiment 4
(compound number is for the synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (2- pyridyl groups) -1,4- pentadiene -3- ketone
N4), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (2- pyridyl groups) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment 1 (2)
Step, difference lies in using 2- pyridine carboxaldehydes as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (2- pyridyl groups) -1,4- pentadiene -3- ketone：Such as embodiment
1 (4) step, difference lies in using 1- (2- pyridyl groups) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
Embodiment 5
Synthesis (the compound number of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- methoxyphenyls) -1,4- pentadiene -3- ketone
For N5), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- methoxyphenyls) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment 1
(2) step, difference lies in using 4-methoxybenzaldehyde as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- methoxyphenyls) -1,4- pentadiene -3- ketone：Strictly according to the facts
1 (4) step of example is applied, difference lies in using 1- (4- methoxyphenyls) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
Embodiment 6
Synthesis (the compound number of 1- (4- (2- quinoxalinyls) phenyl) -5- (2- methoxyphenyls) -1,4- pentadiene -3- ketone
For N6), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (2- methoxyphenyls) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment 1
(2) step, difference lies in using Benzaldehyde,2-methoxy as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (2- methoxyphenyls) -1,4- pentadiene -3- ketone：Strictly according to the facts
1 (4) step of example is applied, difference lies in using 1- (2- methoxyphenyls) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
Embodiment 7
(compound number is for the synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- chlorphenyls) -1,4- pentadiene -3- ketone
N7), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- chlorphenyls) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment 1 (2)
Step, difference lies in using 4- chlorobenzaldehydes as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- chlorphenyls) -1,4- pentadiene -3- ketone：Such as embodiment
1 (4) step, difference lies in using 1- (4- chlorphenyls) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
Embodiment 8
Synthesis (the compound of 1- (4- (2- quinoxalinyls) phenyl) -5- (2,4- Dimethoxyphenyls) -1,4- pentadiene -3- ketone
Number is N8), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (2,4- Dimethoxyphenyls) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment
1 (2) step, difference lies in 2,4- dimethoxy benzaldehydes be raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (2,4- Dimethoxyphenyls) -1,4- pentadiene -3- ketone：
Such as 1 (4) step of embodiment, difference lies in 1- (2,4- Dimethoxyphenyl) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3-
Ketone is raw material.
Embodiment 9
(compound number is for the synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- fluorophenyls) -1,4- pentadiene -3- ketone
N9), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- fluorophenyls) -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as embodiment 1 (2)
Step, difference lies in using 4- fluorobenzaldehydes as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- (4- fluorophenyls) -1,4- pentadiene -3- ketone：Such as embodiment
1 (4) step, difference lies in using 1- (4- fluorophenyls) -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
Embodiment 10
The synthesis (compound number N10) of 1- (4- (2- quinoxalinyls) phenyl) -5- phenyl-Isosorbide-5-Nitrae-pentadiene -3- ketone, including
Following steps：(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：Such as 1 (1) step of embodiment.
(2) synthesis of 1- phenyl -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone：Such as 1 (2) step of embodiment, difference
It is using benzaldehyde as raw material.
(3) synthesis of 2- chloro-quinoxalines：Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (2- quinoxalinyls) phenyl) -5- phenyl -1,4- pentadiene -3- ketone：Such as embodiment 1 (4)
Step, difference lies in using 1- phenyl -5- (4- hydroxy phenyls)-Isosorbide-5-Nitrae-pentadiene -3- ketone as raw material.
The physicochemical property of the Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ketones derivants of synthesis is shown in Table 1, nuclear magnetic resonance spectroscopy
(1H NMR) and carbon spectrum (13C NMR) data are shown in Table 2.
1 target compound physicochemical property of table
2 target compound nuclear magnetic resonance spectroscopy of table and carbon modal data
The antitumor activity of above-mentioned target compound
Test method
A. the processing of the culture of cell strain and medicament：Human hepatocellular SMMC-7721 cells are trained with the RPMI 1640 containing 10%FBS
Base is supported, 37 DEG C, 5%CO are incubated at2Saturated humidity incubator, change liquid every other day, pass within 1-2 days.Compound is dissolved in DMSO works
For storing solution.Before use, being directly diluted to required concentration with culture medium.Blank control group is added and drug same volume
The gemcitabine with concentration with tested drug is added in DMSO, positive controls.DMSO ultimate densities in treatment agent are no more than
0.1% (V/V).
B.MTT colorimetric method extracorporeal anti-tumor medicament screening experiment principles：MTT is a kind of hydrionic dyestuff of receiving, can be made
For the respiratory chain in living cells mitochondria, tetrazolium ring opening under the action of succinate dehydrogenase and cytochrome c generates blue
The first a ceremonial jade-ladle, used in libation of purple crystallizes.The production quantity of first a ceremonial jade-ladle, used in libation crystallization is directly proportional to number of viable cells, and dead cell is without this function.Dimethyl is sub-
Sulfone, SDS can dissolve the crystallization, measure the absorbance at 595nm using microplate reader, can reflect the quantity of living cells indirectly.
Within certain cell context, the quantity for the crystal that MTT is formed is directly proportional to cell number.This method can be used for anti-on a large scale
Tumor drug screening, cytotoxicity experiment and tumor radiosensitivity measurement etc..
C.MTT colorimetric method extracorporeal anti-tumor medicament screening experiment steps：By the secondary water seal of uplink and downlink sterilizing of 96 orifice plates
Side, per 200 μ L of hole.Logarithmic growth phase cell after conventional digestion, is resuspended in 1640 culture mediums of RPMI containing 10%FBS,
With 4 × 104The final concentration of a/mL is inoculated in 96 well culture plates, and per 100 μ L of hole, the rightmost side one is classified as blank control group, adds without thin
Born of the same parents' has 1640 culture mediums of serum RPMI.It is placed in 37 DEG C, 5%CO2Saturated humidity incubator in cultivate and make cell adherent for 24 hours.
Culture medium is sopped up, the concentration containing different pharmaceutical is added has blood serum medium, per 200 μ L of hole, pays attention to DMSO final concentrations in culture medium
No more than 0.1%, blank control group adds 200 μ L complete mediums per hole.The requirement of experiment time is handled respectively, removes supernatant,
Add the MTT of 100 μ L/well concentration 0.5mg/mL.10% SDS of 100 μ L/well is added after culture 4h again.10h makes at 37 DEG C
Crystal takes out after fully dissolving, and 5min is swung in microseism, places 30min at room temperature, OD values is surveyed under A595 wavelength, and calculate cell
Activity, inhibiting rate and P values.
Using drug concentration or processing time as horizontal axis, OD values or inhibiting rate are the longitudinal axis, draw curve.Per concentration of specimens weight
Multiple six holes, each experiment in triplicate, are averaged as final result.
Experimental result carries out variance analysis, p with SPSS softwares<It is significant difference, p when 0.05<It is extremely aobvious for difference when 0.01
It writes.The inhibiting rate calculation formula of cell Proliferation is as follows：
3 target compound of table acts on SMMC-7721 liver cancer cells the extracorporeal inhibiting rate of 72h
Using mtt assay, using commodity medicament gemcitabine as positive control, when test concentrations are 1 μM and 10 μM, target is tested
Inhibitory activity (be shown in Table 3) of the compound to SMMC-7721 liver cancer cells.The test result shows：Most of target compound pair
SMMC-7721 liver cancer cells are presented with good inhibitory activity.At a concentration of 10 μM, series compound (5 He of compound N
Except N7) to the activity suppression ranging from 69.09%~100.00% of SMMC-7721 liver cancer cells, wherein compound N 3 is to liver
The activity suppression of cancer SMMC-7721 cells reaches 100.00%, far superior to comparison medicament gemcitabine (42.52%)；Dense
When degree is 1 μM, which is presented with good inhibitory activity to SMMC-7721 liver cancer cells, and inhibiting rate is above
Comparison medicament gemcitabine (20.16%).Especially compound N 3 and N4 is presented with SMMC-7721 liver cancer cells excellent suppression
System activity, inhibitory activity>90.00%, far superior to gemcitabine (20.16%).
To further appreciate that the active anticancer of such compound, shape of the SMMC-7721 liver cancer cells under Electronic Speculum is had studied
The form for the SMMC-7721 liver cancer cells that inverted microscope recorded after 24,48 and 72h of chemicals treatment is used in combination in state:
Statistics indicate that：Such compound all has significant inhibiting effect to SMMC-7721 liver cancer cells activity.Part of compounds
Inhibitory activity is higher than positive drug (being shown in Table 3) compared with positive drug gemcitabine, in same dosage and action time.It is worth one
It is mentioned that commercialization medicament i.e. positive drug is significantly greater to the toxicity of tumour cell (so that cell all broken cracking), and this hair
The compound of bright synthesis has inhibiting effect to tumour cell at low concentrations, and very little, this inhibitory activity are damaged to target cell
The proliferation (cell quantity obviously tails off compared with the control) for inhibiting cell or Cell differentiation inducing activity are mainly reflected in (from form
Learn observation we it is not difficult to find that cell cell is deformed simultaneously reduced number of, but it is not apparent to damage), but
It is generally to be remarkably reinforced with the raising inhibitory activity of compound concentration.Which part compound is thin to liver cancer SMMC-7721
Born of the same parents have excellent inhibitory activity, can be used as potential anti-tumor agents and use.
The above described is only a preferred embodiment of the present invention, being not intended to limit the present invention in any form, appoint
What is simply repaiied to any made by above example according to the technical essence of the invention without departing from technical solution of the present invention content
Change, equivalent variations and modification, in the range of still falling within technical solution of the present invention.
Claims (3)
1. a kind of Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ketones derivants, general formula are as follows：
Wherein, R1For phenyl, substituted-phenyl or substitution aromatic heterocyclic；R is to contain on 5,6,7 or 8 in quinoxaline structure
More than one hydrogen atom, methoxyl group, nitro, methyl, trifluoromethyl or halogen atom.
2. a kind of preparation method of the Isosorbide-5-Nitrae containing quinoxaline-pentadiene -3- ketones derivants as described in claim 1, including with
Lower step：
(1) using acetone, salicylide or 4- hydroxy benzaldehydes as raw material, 2- (hydroxy phenyl) -3- butylene-is prepared under alkaline condition
2- ketone or 4- (hydroxy phenyl)-3- butene-2 -one:
(2) using substituted aroma aldehyde, 2- (hydroxy phenyl) -3- butene-2s -one or 4- (hydroxy phenyl) -3- butene-2s -one as raw material,
1- substituted aryls -5- (4- hydroxy phenyls) -1,4- pentadiene -3- ketone or 1- substituted aryls -5- (2- hydroxyls are prepared under alkaline condition
Base phenyl) -1,4- pentadiene -3- ketone：
(3) with the 2- chloro-quinoxalines of 2- hydroxy quinoxalines and the preparation of phosphorus oxychloride raw material containing substituent group containing substituent group：
(4) 1- (2- hydroxy phenyls) -5- (substituted aromatic base) -1,4- pentadiene -3- ketone and 1- (4- hydroxy phenyls) -5- (substitutions
Aromatic radical)-Isosorbide-5-Nitrae-pentadiene -3- ketone with containing substituent group 2- chloro-quinoxalines occur etherification reaction, generate the Isosorbide-5-Nitrae-containing quinoxaline
Pentadiene -3- ketones derivants：
。
3. a kind of application of 1,4- pentadiene -3- ketones derivants containing quinoxaline in terms of preparing human body liver-cancer medicine.
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