CN103319431B - 2-mercaptoacetophenone-containing 1, 3, 4-oxadiazole derivative, its preparation method and antitumor activity - Google Patents
2-mercaptoacetophenone-containing 1, 3, 4-oxadiazole derivative, its preparation method and antitumor activity Download PDFInfo
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- 0 *c([o]1)nnc1SCC(c1ccc(*)cc1)=O Chemical compound *c([o]1)nnc1SCC(c1ccc(*)cc1)=O 0.000 description 1
- QXIOWYFFTWXSHE-UHFFFAOYSA-N Cc(c(O)c1)ccc1OC Chemical compound Cc(c(O)c1)ccc1OC QXIOWYFFTWXSHE-UHFFFAOYSA-N 0.000 description 1
- NKTOLZVEWDHZMU-UHFFFAOYSA-N Cc1ccc(C)c(O)c1 Chemical compound Cc1ccc(C)c(O)c1 NKTOLZVEWDHZMU-UHFFFAOYSA-N 0.000 description 1
- MZVSTDHRRYQFGI-UHFFFAOYSA-N Cc1ccnc(Cl)c1 Chemical compound Cc1ccnc(Cl)c1 MZVSTDHRRYQFGI-UHFFFAOYSA-N 0.000 description 1
- ORLGLBZRQYOWNA-UHFFFAOYSA-N Cc1ccnc(N)c1 Chemical compound Cc1ccnc(N)c1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a 2-mercaptoacetophenone-containing 1, 3, 4-oxadiazole derivative and a preparation method thereof. The 2-mercaptoacetophenone-containing 1, 3, 4-oxadiazole derivative has a general formula as the following. In the formula, R1 represents the following, and R2 represents -H or -Br. The derivative is a potential anti-tumor medicine and has an inhibiting effect on MCF-7 and A431, and has a strong inhibitory effect on A431. Therefore, the derivative has the strong inhibitory effect.
Description
Technical field
The present invention relates to contain 1,3,4- oxadiazole derivatives of 2- sulfydryl 1-Phenylethanone .s and preparation method thereof with as antitumor
The purposes of medicine.
Background technology
Ozone (O3) it is oxygen (O2) a kind of isomer, content in an atmosphere only accounts for 1/100000000th, and its concentration is because of sea
Degree of lifting and it is different.Ozone layer is the of a relatively high part of ozone concentration in atmospheric stratosphere, and it is mainly around outside the earth
Portion where 20-25 kilometers height, can absorb the ultraviolet of below the wavelength 306.3nm in sunlight, i.e. part from the ground
UV-B (290～300nm of wavelength) and whole UV-C (wavelength≤290nm), preserve our planet on the mankind and animals and plants exempt from it is short
The injury of ripple ultraviolet.
Since the industrial revolution, the mankind are burnt coal and oil in a large number, discharge countless waste gas to earth atmosphere, wherein
Chlorine fluorine gas (such as freon) high-altitude ozone layer can be destroyed so that global ozone layer is thinning, and some areas even occur in that smelly
Oxygen hole, after ozone layer is destroyed, its ability for absorbing ultraviolet is substantially reduced so that the mankind receive excessive ultraviolet radiation
Chance is greatly increased.Excessive ultraviolet radiation greatly increased the sickness rate of skin carcinoma.Most of cases are ultraviolet with excessive
Beta radiation is relevant.Research shows that the ozone of ozone layer is often lost 1%, and the sickness rate of skin carcinoma will increase by 2%, only in the U.S.,
300 ten thousand skin cancer cases are had more than every year just, loss directly or indirectly is more than 200,000,000 dollars.However, controlling for skin carcinoma
Treatment method, such as operative treatment, radiotherapy and chemotherapy have great limitation.Therefore, find efficient anti-skin
Skin cancer drug and new therapy target become an important and urgent task.
Focal adhesion kinase (focal adhesion kinase, FAK) is a kind of non-receptor TYR protein kinase, is whole
The central element in plain mediated signal transduction path is closed, it can affect cell by adjusting a series of downstream signal after activating
Propagation and survival.In Skin Cell, FAK adjusts the migration of cytoskeleton.Numerous studies show that the high of FAK is expressed and tumor
Transfer, attack it is relevant.Therefore, the compound of suppression FAK can be used as potential anti-skin carcinoma medicament.
1,3,4- oxadiazole is widely used in medicinal chemistry art, and the research of early stage shows, contains 1,3,4- oxadiazoles
Compound has multiple biological activities, such as antiinflammatory, antibacterial, blood sugar lowering etc., in addition, according to Usman Ghani et al., 1,3,4- Evil
Oxadiazole derivative can be used as the inhibitor of TYR kinases.
Thioesters (Thioester) is the chemical substance that a sulphur atom and molecule of acyl covalent bond are formed, and formula is
R-S-CO-R′.Thioester bond is high-energy chemistry key, similar to inner in all biological adenosine triphosphate (ATP) for providing energy in vivo
Energy-rich phosphate bond, all of ester bond forms (include lipid) and is required for the participation of thioesters.These materials take part in intracellular many
The synthesis of kind of material, including peptide, fatty acid, sterin, terpenes, porphyrin and other.In addition, thioesters is in targeting ubiquitination protein degradation
Play an important role in matter.
On the basis of the above, we devise that a series of to contain 1,3,4- oxadiazoles (offer anti-tumor activity) similar with thioesters
The compound of thing (increasing targeting of the compound to receptor protein), it is contemplated that this kind of compound can have good antitumor to live
Property.
The content of the invention
It is an object of the invention to provide 1,3,4- oxadiazole derivatives of class sulfydryl containing a 2- 1-Phenylethanone. and they
Preparation method and purposes.
Technical scheme is as follows：
1,3,4- oxadiazole derivatives of one class sulfydryl containing 2- 1-Phenylethanone., is characterized in that it has below formula：
R in formula1For：
R in formula2For：
——H
——Br
A kind of method of 1,3, the 4- oxadiazole derivatives for preparing the above-mentioned 1-Phenylethanone. of sulfydryl containing 2-, is characterized in that it by under
Row step is constituted：
Step one：Take 1mmol carboxylic acids and add 50mL dehydrated alcohol, and add the concentrated sulphuric acid of 5mL, backflow is overnight.Decompression is steamed
Evaporate, add 20mL water, be extracted with ethyl acetate, and washed with the NaCl of the NaHCO3 and saturation of saturation successively
Wash, be finally dried with anhydrous MgSO4, vacuum distillation is obtained target compound.
Step 2：The ester produced in step one is dissolved in the dehydrated alcohol of 50mL, and adds the hydrazine hydrate of 15ml, returned
Flow through night.Reacted solvent under reduced pressure is distilled, until no liquid flows out, water is added, is obtained hydrazides.
Step 3：The hydrazides obtained in taking 1mmol step 2 is added in the round-bottomed flask of 50mL, is dissolved in the anhydrous second of 30mL
Alcohol, adds equimolar Carbon bisulfide, and (potassium hydroxide) flows back 24 hours in the basic conditions, and reacting coarse product is tied after being dried again
Crystalline substance obtains a series of 2- thio -1,3,4 oxadiazole derivatives.
Step 4：Take 2- obtained by 1mmol step 3 thio -1,3,4 oxadiazole derivatives and equimolar quality 2- bromobenzene
Ethyl ketone/2,4 '-dibromo-benzene ethyl ketone add the round-bottomed flask of 25mL, and are dissolved in 80% ethanol of 5mL, 4-6h is stirred at room temperature, subtracts
Pressure is distilled off unnecessary solvent, then pours reaction crude extract in frozen water into, stands 1-2h, filters, and gained is precipitated by washing
Thing obtains target compound with recrystallizing methanol after being dried.
Test result indicate that, 1,3,4- oxadiazole derivatives of the new 1-Phenylethanone. of sulfydryl containing 2- of the present invention are thin to breast carcinoma
Born of the same parents MCF-7 and cutaneous squamous cell carcinoma cell A431 have inhibitory action, wherein have strong inhibitory action to A431, therefore this
1,3,4- oxadiazole derivatives of the bright 1-Phenylethanone. of sulfydryl containing 2- can apply to prepare anti-skin carcinoma medicament.
Specific embodiment
The present invention is further described by following examples, but the scope of the present invention is not appointed by these embodiments
What limits.
Embodiment one：2- (5- (2- hydroxy-4-methyl phenyl) -1,3,4- oxadiazole -2- are thio) -1- 1-Phenylethanone. (chemical combination
Thing preparation 1).
Take 1mmol 4- cresotic acids and add 50mL dehydrated alcohol, and add the concentrated sulphuric acid of 5mL, backflow is overnight.Decompression
Distillation about remains 1/5th, adds 20mL water, is extracted with ethyl acetate, and is washed with the NaCl of the NaHCO3 and saturation of saturation successively
Wash, be finally dried with anhydrous MgSO4, vacuum distillation is obtained 4- cresotinic acid esters；4- cresotinic acid esters are dissolved in into 50mL
Dehydrated alcohol in, add 15ml hydrazine hydrate, backflow overnight.Reacted solvent under reduced pressure is distilled, until no liquid flow
Go out, add water, obtain 4- cresotinic acid hydrazides；Hydrazides is put in the round-bottomed flask of 50mL, 30mL dehydrated alcohol is dissolved in, plus
Enter the Carbon bisulfide of equimolar quality, (potassium hydroxide) flows back 24 hours in the basic conditions, reacting coarse product is tied after being dried again
Crystalline substance obtains a series of 2- thio -1,3,4 oxadiazole derivatives；Take the 2- thio -1 of equimolar quality, 3,4 oxadiazole derivatives and
2- bromoacetophenones put into the round-bottomed flask of 25mL, and which is dissolved in 80% ethanol of 5mL, and 4-6h, vacuum distillation is stirred at room temperature
Unnecessary solvent is removed, is then poured reaction crude extract in frozen water into, is stood 1-2h, filter, gained sediment is dried by washing
Recrystallizing methanol is used afterwards, obtains target compound.White powder, yield 83%, fusing point：196-198 DEG C,1H NMR (300MHz,
CDCl3-d6)δ：2.39 (d, J=6.03Hz, 3H)；4.98 (s, 2H)；6.82 (d, J=8.07Hz, 1H)；6.93 (t, J=
6.00Hz, 1H)；7.51-7.59 (m, 3H)；7.65 (t, J=7.50Hz, 1H)；8.05 (t, J=4.50Hz, 2H)；9.73 (s,
1H)；MS(ESI)：327.37(C17H15N2O3S, [M+H]+).Anal.Calcd for C17H14N2O3S：C, 62.56；H, 4.32；
N, 8.58；Found：C, 62.48；H, 4.31；N, 8.62.
Embodiment two：2- (5- (4- (dimethylamino) phenyl) -1,3,4- oxadiazole -2- are thio) -1- 1-Phenylethanone. (compounds
2) preparation.
Preparation method replaces 4- cresotic acids, obtains target compound with embodiment one, 4- dimethylaminobenzoic acids.It is yellowish
Color solid, yield 88%, fusing point：203-204 DEG C,1H NMR (300MHz, CDCl3-d6)δ：4.98 (s, 2H)；5.32 (s, 6H)；
7.55 (t, J=7.50Hz, 4H)；7.67 (t, J=7.32Hz, 1H)；7.91 (d, J=8.61Hz, 2H)；8.05 (d, J=
7.68Hz, 2H) .MS (ESI)：340.41(C18H18N3O2S, [M+H]+).Anal.Calcd for C18H17N3O2S：C, 63.70；
H, 5.05；N, 12.38.Found：C, 63.64；H, 5.03；N, 12.44.
Embodiment three：2- (5- (2- hydroxyl -4- toluene) -1,3,4- oxadiazole -2- are thio) -1- 1-Phenylethanone .s (compound 3)
Preparation.
Preparation method replaces 4- cresotic acids with 4- methoxysalicylic acids, obtains target compound with embodiment one.White
Powder, yield 83%, fusing point：195 DEG C,1H NMR (300MHz, CDCl3-d6)δ：3.89 (d, J=13.5Hz；3H)；4.96 (s,
2H)；5.35 (s, 1H)；6.57 (d, J=2.61Hz, 1H)；6.61 (s, 1H), 7.54 (t, J=4.62Hz, 2H)；7.59 (d, J
=2.61Hz；1H)；7.66 (t, J=4.44Hz；1H)；8.05 (d, J=2.39Hz；2H).MS(ESI)：343.37
(C17H15N2O4S, [M+H]+).Anal.Calcd for C17H14N2O4S：C, 59.74；H, 4.22；N, 8.18.Found：C,
59.66；H, 4.23；N, 8.21.
Example IV：The system of 2- (- 1,3,4- oxadiazole -2- of 5- (2- amino piperidines) are thio) -1- 1-Phenylethanone .s (compound 4)
It is standby.
Preparation method replaces 4- cresotic acids with 2- amino -4- picolinic acids, obtains target compound with embodiment one.
Pale yellow powder, 83%. fusing point of yield：208 DEG C,1H NMR (300MHz, CDCl3-d6)δ：5.01 (s, 2H)；7.12 (s, 1H)；
7.23 (d, J=5.76Hz, 1H)；7.54 (t, J=4.62Hz, 3H)；7.66 (s, 2H)；8.05 (d, J=2.11Hz；3H).MS
(ESI)：313.25(C15H13N4O2S, [M+H]+).Anal.Calcd for C15H12N4O2S：C, 57.68；H, 3.87；N,
17.94.Found：C, 57.59；H, 3.88；N, 17.98.
Embodiment five：2- (5- (2- Chloperastine -4- ethyls) -1,3,4- oxadiazole -2- are thio) -1- 1-Phenylethanone. (compounds
5) preparation.
Preparation method replaces 4- cresotic acids with 2- chlorine apellagrins, obtains target compound with embodiment one.White powder,
Yield 81%, fusing point：165 DEG C,1H NMR (300MHz, CDCl3-d6)δ：5.01 (s, 2H)；7.54 (t, J=4.62Hz, 2H)；
7.67 (t, J=4.44Hz, 1H)；7.81 (s, 1H)；7.90 (s, 1H)；8.06 (d, J=4.50Hz；2H)；8.57 (s, 1H) .MS
(ESI)：332.78(C15H11ClN3O2S, [M+H]+).Anal.Calcd for C15H10ClN3O2S：C, 54.40；H, 3.04；N,
12.67；Found：C, 54.36；H, 3.05；N, 12.69.
Embodiment six：1- (4- bromobenzenes) -2- (5- (2- hydroxyl -4- toluene) -1,3,4- oxadiazole -2- are thio) ethyl ketone (is changed
Compound preparation 6).
Take 1mmol 4- cresotic acids and add 50mL dehydrated alcohol, and add the concentrated sulphuric acid of 5mL, backflow is overnight.Decompression
Distillation about remains 1/5th, adds 20mL water, is extracted with ethyl acetate, and successively with the NaHCO of saturation3Wash with the NaCl of saturation
Wash, finally use anhydrous MgSO4It is dried, vacuum distillation is obtained 4- cresotinic acid esters；4- cresotinic acid esters are dissolved in into 50mL
Dehydrated alcohol in, add 15ml hydrazine hydrate, backflow overnight.Reacted solvent under reduced pressure is distilled, until no liquid flow
Go out, add water, obtain 4- cresotinic acid hydrazides；Hydrazides is put in the round-bottomed flask of 50mL, 30mL dehydrated alcohol is dissolved in, plus
Enter the Carbon bisulfide of equimolar quality, (potassium hydroxide) flows back 24 hours in the basic conditions, reacting coarse product is tied after being dried again
Crystalline substance obtains a series of 2- thio -1,3,4 oxadiazole derivatives；Take the 2- thio -1 of equimolar quality, 3,4 oxadiazole derivatives and
2,4 '-dibromo-benzene ethyl ketone puts into the round-bottomed flask of 25mL, and which is dissolved in 80% ethanol of 5mL, 4-6h is stirred at room temperature, subtracts
Pressure is distilled off unnecessary solvent, then pours reaction crude extract in frozen water into, stands 1-2h, filters, and gained is precipitated by washing
Thing uses recrystallizing methanol after being dried, and obtains target compound.White powder, yield 84%, fusing point：237-238 DEG C,1H NMR
(300MHz, CDCl3-d6)δ：2.38 (s, 3H)；4.91 (s, 2H)；6.82 (d, J=8.22Hz, 1H)；6.92 (s, 1H)；7.58
(d, J=8.04Hz, 1H)；7.60 (d, J=8.40Hz, 2H)；7.92 (d, J=8.40Hz, 2H)；9.70 (s, 1H)；MS
(ESI)：406.27(C17H14BrN2O3S, [M+H]+).Anal.Calcd for C17H13BrN2O3S：C, 50.38；H, 3.23；N,
6.91；Found：C, 50.43；H, 3.22；N, 6.89.
Embodiment seven：1- (4- bromobenzenes) -2- (5- (4- (dimethylamino) phenyl) -1,3,4- oxadiazole -2- are thio) ethyl ketone
The preparation of (compound 7).
Amino benzoic Acid replaces 4- cresotic acids, obtains target compound.White powder, yield 85%, fusing point：197-
198 DEG C,1H NMR (300MHz, CDCl3-d6)δ：3.55 (s, 6H)；4.97 (s, 2H)；7.51 (d, J=8.22Hz, 2H)；7.67
(d, J=8.40Hz, 2H)；7.92 (d, J=8.43Hz, 4H) .MS (ESI)：419.31(C18H17BrN3O2S, [M+H]+)
.Anal.Calcd for C18H16BrN3O2S：C, 55.69；H, 4.44；N, 6.49.Found：C, 55.65；H, 4.45；N,
6.45.
Embodiment eight：1- (4- bromobenzenes) -2- (5- (2- hydroxyl -4- toluene) -1,3,4- oxadiazole -2- are thio) ethyl ketone (is changed
Compound preparation 8).
Preparation method replaces 4- cresotic acids with 4- methoxybenzoic acids, obtains target compound with embodiment six.White
Powder, yield 86%, fusing point：229-230 DEG C,1H NMR (300MHz, CDCl3-d6)δ：3.89 (d, J=7.64Hz, 3H)；
4.98 (s, 2H)；5.35 (s, 1H)；6.58 (t, J=6.40Hz, 2H)；7.59 (d, J=8.61Hz, 1H)；7.68 (d, J=
8.58Hz, 2H)；7.92 (d, J=8.61Hz, 2H) .MS (ESI)：422.27(C17H14BrN2O4S, [M+H]+).Anal.Calcd
for C17H13BrN2O4S：C, 48.47；H, 3.11；N, 6.65.Found：C, 48.42；H, 3.12；N, 6.61.
Embodiment nine：2- (5- (2- amino piperidine -4- ethyls) -1,3,4- oxadiazole -2- are thio) -1- (4- bromobenzenes) ethyl ketone
The preparation of (compound 9).
Preparation method replaces 4- cresotic acids with 2- amino 4- picolinic acids, obtains target compound with embodiment six.It is yellow
Color powder, yield 87%, fusing point：200 DEG C,1H NMR (300MHz, CDCl3-d6)δ：4.98 (s, 2H)；7.18 (d, J=
9.15Hz, 1H)；7.35 (d, J=8.80Hz, 1H)；7.59 (d, J=8.61Hz, 2H)；7.68 (d, J=8.43Hz, 1H)；
7.76 (d, J=8.58Hz, 1H)；7.92 (d, J=8.61Hz, 2H)；8.14 (d, J=5.67Hz, 1H) .MS (ESI)：392.24
(C15H12BrN4O2S, [M+H]+).Anal.Calcd for C15H11BrN4O2S：C, 46.05；H, 2.83；N, 14.32.Found：
C, 46.01；H, 2.82；N, 14.37.
Embodiment ten：1- (4- bromobenzenes) -2- (5- (2- Chloperastine -4- ethyls) -1,3,4- oxadiazole -2- are thio) ethyl ketone
The preparation of (compound 10).
Preparation method replaces 4- cresotic acids with 2- chlorine apellagrins, obtains target compound with embodiment six.White powder,
Yield 79%, fusing point：177 DEG C,1H NMR (300MHz, CDCl3-d6)δ：5.01 (s, 2H)；7.54 (t, J=4.62Hz, 2H)；
7.67 (t, J=4.44Hz, 2H)；7.90 (s, 1H)；8.06 (d, J=4.5Hz, 1H)；8.57 (s, 1H) .MS (ESI)：411.67
(C15H10BrClN3O2S, [M+H]+).Anal.Calcd for C15H9BrClN3O2S：C, 43.87；H, 2.21；N,
10.23.Found：C, 43.76；H, 2.22；N, 10.27.
Embodiment 11：1,3,4- oxadiazole derivative antitumor activities of benzoylformaldoxime are dredged containing 2-
1. experiment material and method
1.1 medicines and reagent
Using MTT [3- (and 4,5)-bis- methyl -2- thiazoles-(2,5)-phenyl bromination tetrazole is blue] method to be determining sulfydryl containing 2-
The 1 of 1-Phenylethanone., 503nhibiting concentration of 3, the 4- oxadiazole derivatives to MCF-7 and A431, i.e. IC50。
(1) preparation of culture fluid (per liter)：1. suspension cell：RPMI-1640 one bag of powder of cultures (10.4g), newborn Sanguis Bovis seu Bubali
After clear 100ml, penicillin solution (200,000 U/ml) 0.5ml, Streptomycin Solution (200,000 U/ml) 0.5ml, plus tri-distilled water dissolving, use
5.6% NaHCO3Solution adjusts pH value to 7.2-7.4, is finally settled to 1000ml.Filtration sterilization.2. attached cell：Ibid, then
Add NaHCO32.00g, HEPES2.38g.
(2) preparation of D-Hanks buffer (per liter)：NaCl 8.00g, KCl 0.40g, Na2HPO4·12 H2O
0.06g, KH2PO40.06g, NaHCO30.35g.Autoclaving.
(3) preparation of trypsin solution：Concentration is made into for 0.5% trypsin solution using D-Hanks buffer.Cross and filter
Bacterium.
(4) test the preparation of medicinal liquid：Test sample is made into into storing solution with a small amount of tri-distilled water dissolving, typically empirically most
10 times of preparation storing solutions of high concentration.It is different according to compound dissolution, can directly be dissolved with tri-distilled water, or be helped with a small amount of DMSO
It is molten, then plus tri-distilled water dissolving.Concentration of the DMSO in culture fluid unsuitable excessive, the end of DMSO in the every hole cell suspension after dosing
Concentration is usually no more than 0.05%-0.1%.Storing solution is stored in standby in -20 DEG C of refrigerators.
(5) culture of MCF-7 and A431：For adherent growth cell, cellar culture (contains in RPMI-1640 culture fluid
10% calf serum, 100U/ml streptomycins), put 37 DEG C, 5% CO2Cultivate in incubator, passed on once every 3-4 days.Pass on
When first discard original fluid, then use D-Hanks buffer solutions；Then with 0.5% trypsinization 30 seconds or so, add few
Amount fresh medium terminates digestion；Piping and druming, makes attached cell split away off from culture bottle wall；Pipette appropriate to fresh cultured bottle
In, it is supplemented with fresh medium to original volume (nutrient solution volume is about the 1/10 of culture bottle capacity).
(6) cell incubation：Take the logarithm the above-mentioned tumor cell of trophophase, adjust concentration of cell suspension to be 2 × 104Individual/ml.
Add 100 μ l of cell suspension per hole in 96 well culture plates, put 37 DEG C, 5%CO224h is cultivated in incubator.After culture 24h, press respectively
Design adds medicinal liquid.
(7) dosing：Test medicinal liquid is added separately in each hole according to the Concentraton gradient of ultimate density, each concentration sets
6 parallel holes.Experiment (only plus culture fluid and thin is divided into drug test group (being separately added into the test medicine of variable concentrations), matched group
Born of the same parents, are not added with testing medicine) and blank group (only adding culture fluid, be not added with cell and test medicine).96 orifice plates after by dosing are placed in 37 DEG C,
5%CO248h is cultivated in incubator.
(8) measure of survivaling cell：In 96 orifice plates after 48h has been cultivated, 40 μ l of MTT are added (to be matched somebody with somebody with 40 μ l PBS per hole
Into the MTT of 2.5mg/ml).After 4h is placed at 37 DEG C, supernatant is removed.Add 100 μ l extracting solution (10%SDS-5% isobutyls per hole
Alcohol -0.01M HCl).37 DEG C of overnight incubations, finally, detect the optical density in each hole using automatic microplate reader at 570nm wavelength
(OD values).
Half-inhibition concentration (IC50) drug level that is defined as when 50% tumor cell survival.According to the light for determining
Density (OD values), makes the standard curve of inhibitory rate of cell growth, its corresponding drug level is tried to achieve on standard curve.
Inhibitory action of the table 1.Compound 1-10 to MCF-7 and A431 cells
Claims (3)
1. 1,3,4- oxadiazole derivatives of class sulfydryl containing a 2- 1-Phenylethanone., is characterized in that it has below formula：
R in formula1For：
R in formula2For：
——H
——Br。
2. a kind of method of 1,3,4- oxadiazole derivatives of the 1-Phenylethanone. of sulfydryl containing 2- prepared described in claim 1, which is special
Levy is that it is made up of the following steps：
Step one：Take 1mmol carboxylic acids and add 50mL dehydrated alcohol, and add the concentrated sulphuric acid of 5mL, flow back 12h, vacuum distillation to five
/ mono- volume, adds 20mL water, is extracted with ethyl acetate, and successively with the NaHCO of saturation3Solution and saturation NaCl solution are washed
Wash, finally use anhydrous MgSO4It is dried, vacuum distillation obtains carboxylate；
Step 2：The ester produced in step one is dissolved in the dehydrated alcohol of 50mL, and adds the hydrazine hydrate of 15ml, flowed back
At night, reacted solvent under reduced pressure is distilled, until no liquid flows out, add water, obtain hydrazides；
Step 3：The hydrazides obtained in taking 1mmol step 2 is added in the round-bottomed flask of 50mL, is dissolved in 30mL dehydrated alcohol,
Equimolar Carbon bisulfide is added, potassium hydroxide is added, is flowed back 24 hours, reacting coarse product is recrystallized to give a series of after being dried
2- thio -1,3,4 oxadiazole derivatives；
Step 4：Take 2- obtained by 1mmol step 3 thio -1,3,4 oxadiazole derivatives and equimolar quality 2- bromoacetophenone/
2,4 '-dibromo-benzene ethyl ketone adds the round-bottomed flask of 25mL, and is dissolved in 80% ethanol of 5mL, and 4-6h is stirred at room temperature, and decompression is steamed
Unnecessary solvent is removed in distillation, is then poured reaction crude extract in frozen water into, is stood 1-2h, filters, and gained sediment is done by washing
Target compound is obtained with recrystallizing methanol after dry.
3. 1,3,4- oxadiazole derivatives of the 1-Phenylethanone. of sulfydryl containing 2- described in claim 1 in antitumor drug is prepared should
With.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210076813.XA CN103319431B (en) | 2012-03-22 | 2012-03-22 | 2-mercaptoacetophenone-containing 1, 3, 4-oxadiazole derivative, its preparation method and antitumor activity |
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| CN1660824A (en) * | 2004-12-08 | 2005-08-31 | 贵州大学 | 2-substitution-5-(3,4,5-trialkoxy phenyl)-1,3,4-ramification of thiadiazoles and preparation method and biological activity |
| WO2009078587A2 (en) * | 2007-12-14 | 2009-06-25 | Korea Research Institute Of Bioscience And Biotechnology | Composition for prevention and treatment of cancer containing triazolyl-thio-ethanone derivatives inhibiting activity of protein phosphatases or pharmaceutically acceptable salts thereof as an active ingredient |
| CN101723912A (en) * | 2009-11-13 | 2010-06-09 | 天津理工大学 | 2-[5-(2-hydroxyphenyl)-1,3,4-oxadiazole-2-thioether]-1-acetophenone compounds |
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| CN1660824A (en) * | 2004-12-08 | 2005-08-31 | 贵州大学 | 2-substitution-5-(3,4,5-trialkoxy phenyl)-1,3,4-ramification of thiadiazoles and preparation method and biological activity |
| WO2009078587A2 (en) * | 2007-12-14 | 2009-06-25 | Korea Research Institute Of Bioscience And Biotechnology | Composition for prevention and treatment of cancer containing triazolyl-thio-ethanone derivatives inhibiting activity of protein phosphatases or pharmaceutically acceptable salts thereof as an active ingredient |
| CN101723912A (en) * | 2009-11-13 | 2010-06-09 | 天津理工大学 | 2-[5-(2-hydroxyphenyl)-1,3,4-oxadiazole-2-thioether]-1-acetophenone compounds |
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| 2-[5-(3,4,5-三甲氧基苯基)-1,3,4-噻二唑-2-基硫代]-1-(2,3,4-三甲氧基)苯乙酮肟醚合成与抗烟草花叶病毒活性研究;薛伟等;《有机化学》;20061231;第26卷(第5期);第702-706页 * |
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