CN106008390B - A kind of sulfenyl of oxadiazole containing 1,3,4- acetamide derivative, preparation method and applications - Google Patents
A kind of sulfenyl of oxadiazole containing 1,3,4- acetamide derivative, preparation method and applications Download PDFInfo
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- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
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- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
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Abstract
The invention discloses one kind containing 1,3,4 oxadiazole sulfenyl acetamide derivatives, preparation method and applications, general structure（I）It is as follows：In I formulas：R1For substituted arene, substituted benzyl；R2For substituted arene；With preferable anti-vegetative bacteria and anti-phytoviral activity and stabilization.Available for antibacterium and antiviral drug and medicament.
Description
Technical field
The present invention relates to technical field of chemistry, relate in particular to a kind of containing 1,3,4- oxadiazole sulfenyl acetamide derivatives
It also relates to the preparation method for containing 1,3,4- oxadiazole sulfenyl acetamide structure derivatives and this contains 1,3,4- oxadiazole sulphur
Application of the derivative of yl acetamide structure in terms of anti-vegetative bacteria and resisting tobacco mosaic virus.
Background technology
1,3,4- oxadiazole class compound is widely studied because with unique bioactivity and when optical activity, such change
It closes object to be widely used in fields such as pesticide, medicine, materials, such drug of commercialization at present has Chu Cao Ji Evil humulones and kills
Chong Ji Evil worm ketone, 1,3,4- oxadiazole rings are introduced into different compound structures, a series of tools can be generated by structural modification
There is the compound of broad-spectrum biological activity, it plays an increasingly important role in novel agrochemical initiative.1,3,4- oxadiazole classes
Compound is a kind of important derivative in heterocyclic chemistry, because its with good pharmaceutical activity such as, it is antibacterium, anti-true
Bacterium, antiviral, anti-inflammatory, antianxiety and treating tuberculosis etc..
In terms of antibacterium, 2012, Xu etc. (J. Agric. Food Chem., 2012, 60, 1036
1041.) a series of 2- are reported and replace -1,3,4- oxadiazole sulfone compounds, antibacterial activity test shows
Such compound has good inhibitory activity to tobacco blight bacterium, and which part compound is in a concentration of 200 μ g/mL to cigarette
The inhibiting rate of careless Ralstonia solanacearum has reached 100.0%.2015, Li et al. (Bioorg. Med. Chem. Lett., 2015, 25,
481-484.) report a series of 2- sulfydryls-5- substitution 1,3,4-oxadiazole compound, biological activity test the result shows that,
Majority of compounds has good inhibitory activity, wherein compound 2- mercaptos to rice leaf spot bacteria and ralstonia solanacearum of tomato
Base -5- (4- fluorophenyls) -1,3,4- oxadiazoles are to the Ec of rice leaf spot bacteria and ralstonia solanacearum of tomato50Respectively 17.20
± 1.76 μG/mL and 41.37 ± 4.51μG/mL is below the Ec that comparison medicament thiophene bacterium ketone and leaf are sat in boredom50（59.69 ±
2.53 μG/mL, 99.80 ± 4.72μg/mL）
At antimycotic aspect, 2007, Chen etc. (Bioorg. Med. Chem., 2007, 15, 3981
- 3989.) 5- (3,4,5- trimethoxyphenyl) -2- sulfonyls -1,3 are reported, 4- oxadiazole compounds,
Antimycotic bioactivity shows a concentration of 50μDuring g/mL, to fusarium graminearum, botrytis cinerea pers and sclerotinia sclerotiorum
The inhibiting rate of bacterium is respectively：55.8%th, 100.0%, 100.0% is better than comparison medicament hymexazol (52.9%, 75.4%, 77.5%).
2008, Liu et al. (Bioorg. Med. Chem., 2008, 16, 3632-3640.) synthesized it is a series of containing trimethoxy
Base phenyl substitution 1,3,4- oxadiazole class compounds, antimycotic bioactivity the result shows that, 5- (3,4,5- trimethoxy-benzenes
Base) -2- sulfuryls-benzyl -1,3,4- oxadiazoles are a concentration of 50μDuring g/mL, to fusarium graminearum, capsicum wilt bacterium, apple
The inhibiting rate that fruit rotten pathogenic bacteria is respectively provided with preferable inhibitory activity wherein compound is respectively 53.3%, 52.3%, 56.1% slightly lower
In comparison medicament Hymexozole to the inhibiting rate (53.7%, 52.1%, 59.0%) of three kinds of germs.2014, Li et al.
(Bioorg. Med. Chem. Lett., 2014, 24, 1677-1680.) and a series of 5- substituted benzyls -2- sulfonyls of synthesis
Replace -1,3,4- oxadiazole class compounds, biological activity test the result shows that such compound to Rhizoctonia solani Kuhn and rice blast
Germ has preferable inhibitory activity, and compound 4- luorobenzyl -2- mesyls -1,3,4- oxadiazole classes are to Rhizoctonia solani Kuhn
All there is good inhibitory activity, EC with Pyricularia oryzae50Value is respectively 1.1μG/mL and 7.1μg/mL。
In terms of anti-vegetative bacteria, 2013, Bao etc. (Chin. J. Org. Chem., 2013, 33, 995-
999.）Synthesized some row containing 1,3,4- oxadiazole thio-ether units novel 1,2,4- triazols [1,5-a] pyridine derivatives,
Resisting tobacco mosaic virus test result shows that such compound has certain antiviral activity.2013, Xu etc. (Bioorg. Med. Chem. Lett., 2013, 23, 5821-5824.) and synthesize a series of thiadiazoles containing 1,2,3- and 1,3,4- Evil
Diazoles compound, resisting tobacco mosaic virus test result show：Such compound has good antiviral activity, 500μUnder g/mL concentration, part of compounds be respectively to the passivation activity of tobacco mosaic virus (TMV) 90.3% and 85.5% slightly below comparison medicine
Agent Ningnanmycin (92.5%).
In conclusion 1,3,4- oxadiazole sulfone compounds show preferable antibacterium, antimycotic and antiviral activity,
But 1,3,4- oxadiazole sulfone compounds are unstable apt to deteriorate.
Invention content
It is provided a kind of with preferable anti-vegetative bacteria and Antiphytoviral it is an object of the invention to overcome disadvantages mentioned above
Activity and the sulfenyl acetamide derivative of oxadiazole containing 1,3,4- stablized.
Another object of the present invention is to provide the preparation method of the sulfenyl acetamide derivative of oxadiazole containing 1,3,4-.
It is still another object of the present invention to provide the sulfenyl acetamide derivative of oxadiazole containing 1,3,4- in anti-vegetative bacteria
And the application of anti-virus aspect.
Particularly in terms of resisting tobacco mosaic virus and rice leaf spot bacteria, tobacco ralstonia solanacearum and citrus processing
Application.
The present invention's contains 1,3,4- oxadiazole sulfenyl acetamide derivatives, general structure（I）It is as follows：
I
In formula：R1For substituted arene, substituted benzyl；R2For substituted arene；
It is preferred that：
R1It is o-, m- selected from o-, m-, contraposition aryl substituted with halogen, align halogen substituted benzyl；
R2It is o-, m- to replacing halogen aryl selected from o-, m-, it is o-, m- to replacing alkylaryl, to substituted alkoxy virtue
Base, it is o-, m-, to replacing nitroaryl；The halogen atom is fluorine, chlorine, bromine, iodine；
Preferred compound is as shown in table 1：
1. compound number of table and structure
One kind of the present invention contains 1,3,4- oxadiazole sulfenyl acetamide derivatives, and preparation method is as follows：
One kind sulfenyl of oxadiazole containing 1,3,4- acetamide derivative of the invention is for antibacterium and antiviral drug and medicine
Application in terms of agent.
The sulfenyl acetamide derivative of oxadiazole containing 1,3,4- is in terms of resisting tobacco mosaic virus and rice is white for one kind of the invention
The application of leaf spoting bacteria, tobacco ralstonia solanacearum and citrus processing.
Compared with prior art, the present invention with apparent advantageous effect, it was found from technical solution：By containing to a series of
The synthesis of 1,3,4- oxadiazole sulfenyl acetamide derivatives simultaneously tests the analog derivative in anti-vegetative bacteria and Antiphytoviral
Activity, test result show that such has preferable resisting tobacco mosaic virus containing 1,3,4- oxadiazole sulfenyl acetamide derivatives
Activity simultaneously also maintain certain antibacterial activity.
Specific implementation method
Embodiment 1：N(4- fluorophenyls) -2- (5- (4- chlorphenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide (A-
1), include the following steps：
（1）The preparation of 4- chlorobenzoic acid ethyl esters
2 g (12.77mmol) 4- chlorobenzoic acids are added in 100 mL round-bottomed flasks, add 50 mL ethanol solutions, and drip
Add 1 mL (20.1 mmol) concentrated sulfuric acid, be heated to reflux 5 h, TLC detection reactions terminate, and saturated sodium carbonate solution tune pH to 7 is left
The right side, dichloromethane (30 mL × 3) extraction merge organic phase, anhydrous sodium sulfate drying, precipitation, column chromatography (PE：EA=10：1,
V/V 2.0 g of yellow oily liquid, yield 93.4%) are obtained.
（2）The preparation of 4- chlorobenzoyl hydrazines
2 g (10.83 mmol) 4- chlorobenzoic acid ethyl esters are added in 100 mL round-bottomed flasks, 50 mL absolute ethyl alcohols are made
For solvent, 1.08 g (21.67 mmol) 80% hydrazine hydrate is added in, it is 80 that system is placed in oil bath temperatureoUnder C, it is heated to reflux
6 h, TLC detection reaction terminate, and vacuum distillation removes solvent, and 30 mL pure water are added in into system, are extracted with dichloromethane,
Finally obtain 1.7 g of white solid, yield 91.9%, fusing point 162-164oC。
（3）The preparation of 5- (4- chlorphenyls) -1,3,4- oxadiazole -2- mercaptan
1.5 g (8.79mmol) 4- chlorobenzoyls hydrazine and 0.74g are added in 100 mL round-bottomed flasks（13.2 mmol）Hydrogen
Potassium oxide, and the dissolving of 50 mL methanol is added in, 0.8mL (13.19 mmol) carbon disulfide is added dropwise, stirs 12 at ambient temperature
Hour, 0.49 g (8.8 mmol) potassium hydroxide is added, is 80 in oil bath temperatureo8 h are heated to reflux under C, TLC detections are anti-
After answering, vacuum distillation removes solvent, adds in 30 mL pure water, and it is 2 ~ 3 to adjust pH value with 1M HCl, and system is precipitated a large amount of
Faint yellow solid filters, and washes, and drying, ethyl alcohol recrystallization obtains 1.51 g of faint yellow solid, yield 88.7%, fusing point：175-
176oC。
（4）2- is bromo-NThe preparation of (4- fluorophenyls) acetamide
2 g (18.00 mmol) 4- fluoroanilines, 30mL dichloromethane, in ice bath item are added in 100 mL three-necked flasks
2.04 mL (23.40 mmol) bromoacetyl bromide is slowly dropped under part, after completion of dropwise addition, 2h, TLC is stirred at room temperature in system
Detection reaction terminates, and adds in 30 mL pure water, filters, washes to obtain 3.98 g of yellow solid, 95.3 % of yield, fusing point：137-
138 oC。
（5）NThe preparation of (4- fluorophenyls) -2- (5- (4- chlorphenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide
0.20 g (0.94 mmol) 5- is added in 100 mL three-necked flasks（4- chlorphenyls）- 1,3,4- oxadiazoles -2-
Mercaptan, 0.16 g（1.13 mmol）As solvent, stirring makes 5- for potassium carbonate and 15mL acetone（4- chlorphenyls）- 1,3,4- Evil
Diazole -2- mercaptan is completely dissolved, and it is bromo- that 0.22 g (0.94 mmol) 2- is then added in into systemN(4- fluorophenyls) acetyl
Amine.6 h are stirred at room temperature, and a large amount of white solids are precipitated in system, and TLC detection reactions terminate, add in 10 mL ice water and continue stirring 1
H is filtered, and washing obtains 0.24 g yields of white powdery solids：71.0%, fusing point：199-200°C.
The present invention contains the processing step and process conditions of 1,3,4- oxadiazole sulfenyl acetamide derivatives, N- (4- fluorobenzene
Base) illustrate for -2- (- 1,3,4- oxadiazole -2- bases of 5- (4- chlorphenyls)) sulfenyl acetamide, other difference substitutions R1And R2With
This is with reference to synthesis.
Embodiment 2：N(4- chlorphenyls) -2- (5- (4- chlorphenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide synthesizes
(A-2)
（1）The preparation of 4- chlorobenzoic acid ethyl esters
Such as embodiment 1 (1) method and condition
（2）The preparation of 4- chlorobenzoyl hydrazines
Such as embodiment 1 (2) method and condition
（3）The preparation of 5- (4- chlorphenyls) -1,3,4- oxadiazole -2- mercaptan
As embodiment 1 (3) method and condition synthesizes.
（4）2- is bromo-NThe preparation of (4- chlorphenyls) acetamide
If embodiment 1 (4) method and condition synthesizes, difference lies in will（18.00 mmol）4- fluoroanilines are changed to (15.68
Mmol) 4- chloroanilines
（5）NThe preparation of (4- chlorphenyls) -2- (5- (4- chlorphenyls) -1,3,4- oxadiazole -2- bases) thioacetamide
If embodiment 1 (5) method and condition synthesizes, difference lies in by (0.94 mmol) 2- bromo- N- (4- fluorophenyls) second
Amide is changed to (0.94 mmol) 2- bromo- N- (4- chlorphenyls) acetamide.
Embodiment 3：N(4- fluorophenyls) -2- (5- (2- chlorphenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide (A-
7)
（1）The preparation of 2- chlorobenzoic acid ethyl esters
If embodiment 1 (1) method and condition synthesizes, difference lies in be changed to (12.77mmol) 4- chlorobenzoic acids
(12.77mmol) 2- chlorobenzoic acids.
（2）The preparation of 2- chlorobenzoyl hydrazines
If embodiment 1 (2) method and condition synthesizes, difference lies in be changed to (10.83 mmol) 4- chlorobenzoic acid ethyl esters
(10.83 mmol) 4- chlorobenzoic acid ethyl esters.
（3）5-（2- chlorphenyls）The preparation of -1,3,4- oxadiazole -2- mercaptan
If embodiment 1 (3) method and condition synthesizes, difference lies in be changed to (8.79 mmol) 4- chlorobenzoyl hydrazines
(8.79 mmol) 2- chlorobenzoyl hydrazines.
（4）2- is bromo-N(4- fluorophenyls) acetamide such as embodiment 1 (4) method and condition synthesizes.
（5）NThe preparation of (4- fluorophenyls) -2- (5- (2- chlorphenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide
If embodiment 1 (5) method and condition synthesizes, difference lies in will（0.94 mmol) 5- (4- chlorphenyls) -1,3,4-
Oxadiazole -2- mercaptan is changed to（0.94 mmol) 5- (2- chlorphenyls) -1,3,4- oxadiazole -2- mercaptan.
Embodiment 4：N(4- chlorphenyls) -2- (5- (2- chlorphenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide (A-
8)
（1）The preparation of 2- chlorobenzoic acid ethyl esters
As embodiment 3 (1) method and condition synthesizes.
（2）The preparation of 2- chlorobenzoyl hydrazines
As embodiment 3 (2) method and condition synthesizes.
（3）5-（2- chlorphenyls）The preparation of -1,3,4- oxadiazole -2- mercaptan
If embodiment 3 (3) method and condition synthesizes,
（4）2- is bromo-NThe preparation of (4- chlorphenyls) acetamide
If embodiment 2 (4) method and condition synthesizes,
（5）NThe preparation of (4- chlorphenyls) -2- (5- (2- chlorphenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide
If embodiment 1 (5) method and condition synthesizes, difference lies in will（0.94 mmol) 5- (4- chlorphenyls) -1,3,4-
Oxadiazole -2- mercaptan is changed to -1,3,4- oxadiazole -2- mercaptan of (0.94 mmol) 5- (2- chlorphenyls), by (0.94 mmol)
The bromo- N- of 2- (4- fluorophenyls) acetamide is changed to (0.94 mmol) 2- bromo- N- (4- chlorphenyls) acetamide.
Embodiment 5:N(4- fluorophenyls) -2- (5- (4- chlorobenzyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide (A-
19)
（1）The preparation of 4- chlorobenzene acetic acid ethyl esters
If embodiment 1 (1) method and condition synthesizes, difference lies in be changed to (12.77 mmol) 4- chlorobenzoic acids
(11.72 mmol) 4- chlorobenzene acetic acids.
（2）The preparation of 4- chlorobenzene acethydrazides
If embodiment 1 (2) method and condition synthesizes, difference lies in be changed to (10.83 mmol) 4- chlorobenzene acetic acid ethyl esters
(10.07mmol) 4- chlorobenzene acetic acid ethyl esters
（3）The preparation of 5- (4- chlorobenzyls) -1,3,4- oxadiazole -2- mercaptan
If embodiment 1 (3) method and condition synthesizes, difference lies in be changed to (8.79 mmol) 4- chlorobenzoyl hydrazines to change
For (8.12 mmol) phenylacetyl hydrazine.
（4）2- is bromo-N(4- fluorophenyls) acetamide
As embodiment 1 (4) method and condition synthesizes.
（5）NThe preparation of (4- fluorophenyls) -2- (5- (4- chlorobenzyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide
If embodiment 1 (5) method and condition synthesizes, difference lies in by (0.94 mmol) 5- (4- chlorphenyls) -1,3,4-
Oxadiazole -2- mercaptan is changed to (0.88 mmol) 5- (4- chlorobenzyls) -1,3,4- oxadiazole -2- mercaptan.
Embodiment 6：N(4- fluorophenyls) -2- (5- (4- fluorophenyls) -1,3,4- oxadiazole -2- bases) sulfenyl acetamide (A-
25)
（1）The preparation of 4- ethyl fluoro benzoates such as embodiment 1 (1) method and condition, difference lies in by (12.77 mmol)
4- chlorobenzoic acids are changed to (14.27 mmol) 4- fluobenzoic acids.
（2）The preparation of 4- chlorobenzoyl hydrazines such as embodiment 1 (2) method and condition, difference lies in by (10.83 mmol)
4- chlorobenzoyl hydrazines are changed to (11.89 mmol) 4- fluorobenzoyl hydrazines.
（3）The preparation of 5- (4- chlorphenyls) -1,3,4- oxadiazole -2- mercaptan
If embodiment 1 (3) method and condition synthesizes, difference lies in be changed to (8.79 mmol) 4- chlorobenzoyl hydrazines
(9.73 mmol) 4- fluorobenzoyl hydrazines.
（4）2- is bromo-NThe preparation of (4- chlorphenyls) acetamide
As embodiment 1 (4) method and condition synthesizes.
（5）NThe preparation of (4- fluorophenyls) -2- (5- (4- fluorophenyls) -1,3,4- oxadiazole -2- bases) thioacetamide
If embodiment 1 (5) method and condition synthesizes, difference lies in by (0.94 mmol) 5- (4- chlorphenyls) -1,3,4-
Oxadiazole -2- mercaptan is changed to (1.02 mmol) 5- (4- chlorphenyls) -1,3,4- oxadiazole -2- mercaptan.
Synthetic method more than utilization chooses different substituted benzoic acids as raw material, be esterified through ethyl alcohol, hydrazinolysis, cyclisation and
Acidification obtains 5- substituted-phenyl -1,3,4- oxadiazole -2- mercaptan.On the other hand using 4- substituted anilines as raw material, with bromoacetyl bromide
It is bromo- that intermediate 2- is obtained by the reaction under condition of ice bathN(4- substituted-phenyls) acetamide, intermediate 5- substituted-phenyls -1,3,4- Evil
Diazole -2- mercaptan and intermediate 2- are bromo-NThe sulfenyl acetamide of oxadiazole containing 1,3,4- is obtained by the reaction in (4- substituted-phenyls) acetamide
Derivative（That is compound A-1 ~ A-30）.
Preferably synthetic contains 1,3,4- oxadiazole sulfenyl acetamide derivatives, and physicochemical data is such as：State, fusing point, nuclear-magnetism
Data, mass spectrum and infrared spectrum (IR) data it is as shown in table 2.
Test example 1：The activity of resisting tobacco mosaic virus experiment of target compound
The anti-phytoviral activity of compound is measured using half half tikka method.Accurately 3 mg test compounds are weighed in title
In measuring bottle, adding in 60 μ L of solvent DMSO makes it fully dissolve.It is made into the redistilled water containing 1 % Tween 20
The compound solution of 500 mg/L.It is another to take 250 μ L, 2 % Ningnanmycin aquas, 60 μ L of solvent DMSO are added in, containing 1 %
10 mL of redistilled water of Tween 20 is made into the Ningnanmycin solution of 500 mg/L.
The live body therapeutic activity that medicament infects TMV.The consistent Nicotiana glutinosa of growing way is chosen, first dips virus liquid with spread pen
(a concentration of 6 × 10-3 mg/mL), blade face (full leaf) along its artificial frictional inoculation in offshoot direction in the leaf sprinkled with diamond dust
On piece, the inoculation dynamics of left and right blade are consistent as possible, are supported below blade with smooth plank.After virus liquid is done, with stream
Water rinses out the diamond dust above blade.After blade is done, medicament is spread in Zuo Banye, right half leaf spreads aqua sterilisa and compares.
3 plants are set per chemicals treatment, plant is then placed on moisturizing culture in illumination box by every plant of 3-4 piece leaf, controls temperature
23 ± 1 °C, the number for generating withered spot is observed and recorded after illumination 10000 Lux, 2-4 d.It is carried out as stated above per medicament
3 repetitions calculate inhibiting rate.
The live body protection activity that medicament infects TMV.The consistent Nicotiana glutinosa of growing way is chosen, is gently applied with writing brush in Zuo Banye
Dispenser agent, right half leaf spread aqua sterilisa and compare, virus inoculation after 24 hours.With spread pen dip viral juice (a concentration of 6 ×
10-3 mg/mL), blade face (full leaf) along its artificial frictional inoculation in offshoot direction on the blade sprinkled with diamond dust, left and right leaf
The inoculation dynamics of piece is consistent as possible, is supported below blade with smooth plank.After virus liquid is done, blade is rinsed out with flowing water
Diamond dust above.Each chemicals treatment sets 3 plants of Nicotiana glutinosas, and plant is then placed on illumination box by every plant of 3-4 piece leaf
Middle moisturizing culture controls 23 ± 1 °C of temperature, the number for generating withered spot is observed and recorded after illumination 10000 Lux, 2-4 d
Mesh.3 repetitions are carried out per medicament as stated above, calculate inhibiting rate.
Y(%)=(R-L)/R×100%
Wherein：Y is compound to the inhibiting rate to tobacco mosaic virus (TMV)；R is control group (right half leaf) withered spot number,；L
For processing group (Zuo Banye) withered spot number.The embodiment of the present invention, which is aided with, illustrates technical scheme of the present invention, but the content of embodiment
It is not limited thereto, experimental result such as table 3, shown in table 4.
Note：A be it is every processing in triplicate b using commercially available medicine Ningnanmycin as positive control.
The result shows that a concentration of 500μG/mL majority of compounds has preferable therapeutic activity for TMV, wherein
Compound A-8, A-10, A-20, A-23, A-27 are respectively 59.8% to the therapeutic activity of TMV, 57.5%, 57.5%, 60.2%,
57.3%, 57.4%, it is suitable with comparison medicament Ningnanmycin (57.9%) activity.And majority of compounds is respectively provided with certain guarantor
Shield activity.
Test example 2：Anti- TMV therapeutic activities EC50Value measures
Test method：It weighs in the balance and takes 3.00 mg test compounds in measuring cup, and add in 6.0 mL, 1% tweens,
Oscillation shakes up rear a concentration of 500μg/mL；Wherein 3.0 mL are taken out in another measuring cup, add in 3.0 mL, 1% tweens
Oscillation shakes up rear a concentration of 250μg/mL；Wherein 3.0 mL are taken out in another measuring cup, add in 3.0 mL, 1% tweens
Oscillation shakes up rear a concentration of 125μg/mL；Wherein 3.0 mL are taken out in another measuring cup, add in 3.0 mL, 1% tweens
Oscillation shakes up rear a concentration of 62.5μg/mL；Wherein 3.0 mL are taken out in another measuring cup, 3.0 mL 1% is added in and spits
Temperature, oscillation shake up rear a concentration of 31.25μg/mL.50.0 mL of comparison medicine Ningnanmycin is taken in measuring cup, adds in 8.0 mL
1% tween, oscillation shake up rear a concentration of 500μG/mL obtains a concentration of 250 successively according to the method described aboveμg/mL、125 μ
g/mL、62.5 μG/mL and 31.25μg/mL。
According to the experimental method of Antiphytoviral therapeutic activity, respectively to 5 concentration of test compound and Ningnanmycin
Anti- TMV therapeutic activities test is carried out, calculates the inhibiting rate under 5 concentration respectively.According to EC50Software for calculation each confession is obtained
Try compound and the EC50 values of Ningnanmycin
Compound A-8 as can be seen from Table 4, A-20 have preferable therapeutic activity to tobacco mosaic virus (TMV) (TMV)
EC50 values are respectively 239.5,236.2μG/mL is less than comparison medicament Ningnanmycin（EC50 values are 273.2μg/mL）, compound
The EC50 values of A-10, A-12, A-20, A-23, A-27, A-29 are respectively 284.5,293.6,284.3,278.0,274.9,
275.3 μG/mL is suitable with comparison medicament Ningnanmycin.
Test example 3：The suppression bacterial activity experiment of compound
Target compound and comparison medicament are weighed respectively in DMSO, are prepared 5% solution, are taken 80 respectivelyμL、40 μL solution
In containing 4 mL NB culture mediums (beef extract 3g, peptone 5g, yeast extract 1g, 10 g of glucose, secondary water 1L, pH=7.0-
7.2) in test tube, solution will be prepared and take out 200μL spectrophotometric determination OD values, add 40μL has shaken bacterium solution, in
30 DEG C, 24 h are cultivated in 180rpm constant-temperature tables.End to be tested takes out 200 in test tubeμL and with spectrophotometric determination OD
Value, caused error is corrected comparison medicament in itself, and the calculation formula for correcting OD values and preventive effect is as follows：
Correct OD values：The values of OD containing bacterium culture medium-aseptic culture medium OD values
Training is compareed after preventive effect %=(control medium bacterium solution OD values-correction pastille culture medium bacterium solution OD values after correction)/correction
Support base bacterium solution OD value × 100
The embodiment of the present invention, which is aided with, illustrates technical scheme of the present invention, but the content of embodiment is not limited thereto, experiment
As a result shown in table 5.
5. target compound of table is to rice leaf spot bacteria, the inhibitory activity of tobacco ralstonia solanacearum and citrus processing
As can be seen from Table 5, a concentration of 200μDuring g/mL major part A classes compound to rice leaf spot bacteria and
Citrus processing has certain inhibitory activity, compound A-1, A-2, A-3, A-4, A-8, A-10, A-13, A-16, A-17,
The inhibitory activity of A-18, A-20, A-22, A-24, A-25, A-26, A-27, A-28, A-29 are above comparison medicament Yekuzuo
(56.1%), inhibitory activity is preferably respectively 96.2% and 95.9% far above comparison medicament Yekuzuo during compound A-16 and A-29；
Wherein compound A-1 and A-20 can reach the inhibitory activity of citrus processing more than 70%, compound A-3, A-4, A-6,
A-9, A-12, A-13, A-14, A-15, A-16, A-18, A-19, A-21, A-24, A-7, A-8, A-9, A-30 are to citrus bacterial canker disease
The inhibitory activity of bacterium is all higher than comparison medicament thiophene bacterium ketone（22.7%）.Wherein compound A-20, A-24 is in a concentration of 100 μ g/mL
When remain to arrival 60% to the inhibitory activity of c itrus canker, and most of target compound is green to tobacco withered does not inhibit significantly
Activity.
The above described is only a preferred embodiment of the present invention, not making limitation in any form to the present invention, appoint
Without departing from technical solution of the present invention content, technical spirit according to the present invention any is simply repaiied to what above example was made for what
Change, equivalent variations and modification, in the range of still falling within technical solution of the present invention.
Claims (1)
1. a kind of sulfenyl acetamide derivative of oxadiazole containing 1,3,4- is used to prepare resisting tobacco mosaic virus, bacterial blight of rice
Application in terms of the drug and medicament of bacterium, tobacco ralstonia solanacearum and citrus processing, it is described to contain 1,3,4- oxadiazole sulfenyl second
The concrete structure of amide derivatives is as shown in table 1：
1. compound number of table and structure
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