CN107513059A - A kind of 23 azacyclo- Thiochromone compounds of substitution and its synthetic method and the application in antifungal drug - Google Patents

A kind of 23 azacyclo- Thiochromone compounds of substitution and its synthetic method and the application in antifungal drug Download PDF

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CN107513059A
CN107513059A CN201610450799.3A CN201610450799A CN107513059A CN 107513059 A CN107513059 A CN 107513059A CN 201610450799 A CN201610450799 A CN 201610450799A CN 107513059 A CN107513059 A CN 107513059A
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compound
hydrogen
alkyl
thiochromone
azacyclo
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肖涛
胡彪
陈国策
冯议
魏芳
肖子煜
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Nanjing Tech University
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Nanjing Tech University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Abstract

The present invention relates to one kind 2 to substitute 3 azacyclo- Thiochromone compounds to have following structure：Wherein R2It is hydrogen, oxyl, hydrocarbon amino, C1‑C3The penta azacyclo of alkyl substitution；R3It is the five yuan of nitrogenous heteroaromatics substituted by hydrogen, methyl, nitro or cyano group；R4、R5、R7It is independently selected from hydrogen, fluorine, chlorine, bromine or iodine；R6Selected from hydrogen, fluorine, chlorine, bromine, iodine, C1‑C6Oxyl, C1‑C6Hydrocarbon amino, phenoxy group, by one or more C1‑C6Alkyl or C1‑C6The phenoxy group of oxyl substitution.The compound of the present invention, which has, prepares antifungal drug purposes, all has stronger bacteriostatic activity to common causative fungi and deep fungal infection, and toxicity is low, stability is good, anti-fungus spectra is wide.

Description

A kind of 2- substitutions -3- azacyclo-s Thiochromone compound and its synthetic method and anti- Application in fungi-medicine
Technical field
The present invention relates to a kind of antimycotic 2- substitutions -3- azacyclo-s Thiochromone compound and its synthetic method and its Prepare the application in antifungal drug.
Background technology
In recent years, widely using due to broad-spectrum antibiotic, immunodepressant and all kinds of hormone medicines, and putting The reasons such as treatment, organ transplant and infected by HIV cause human immune system's function reduction, and the probability for causing body fungal infection increases Add, so as to cause the morbidity and mortality of fungal diseases constantly to rise.Drug resistance present in other clinical treatment and anti- The problems such as bacterium spectrum is narrow, also increase the treatment difficulty of fungal infection class disease.Therefore develop wide spectrum, efficiently, low toxicity it is new Antifungal drug, it has been the sciences problems for being badly in need of solving.
Activity research shows that Thiochromone compound has obvious antifungal activity, at present the thiochromone of document report Class compound, more with synthesis obtain based on.Early in 1976, Hiroyuki NakazuMi et al. just reported the sulphur of its synthesis Chromone compounds；Square woods in 1998 et al. is in its document, it was recently reported that 6,7 halos and 1 thioether bond are oxidized to sulfone The synthesis of sulphur color (full) ketone and its antifungal activity；1998, Yu Xinrui et al. described 3- benzyl -6- chlorine in its document The synthesis of thiochromanone and antifungal activity；2007, Huang Wei et al. designed a series of thiochromone class for having synthesized 2 sulfur-bearings Compound, describe seven kinds of mycologic tests such as external anti-Fusarium oxysporum and show bacteriostatic activity, 2009, Xiao Tao et al. was in thiochromone 2 introducing sulfenyls of class compound, describe such compound to common causative fungi and deep fungal infection with stronger Antibacterial and antifungal activity etc..
Chromone and Thiochromone compound, because of the special chemical constitution and bioactivity that it has, the world is caused The extensive concern of upper medicine researcher.Either natural extract or synthetic product, antibacterial new target spot and mechanism of action are Through as research direction important at present.Recent decades, with computer aided molecular design technology, bioactivity screening skill The application of the new technologies such as art, molecular biology, genomics and ripe day by day, the research and development for greatly accelerating antifungal drug are entered Degree.It is contemplated that deepening continuously with research, has more efficient, low toxicities, the antifungal drug of wide spectrum is developed and made Good fortune is in the mankind.
The content of the invention
It is an object of the present invention to provide a kind of 2- substitutions -3- azacyclo-s Thiochromone compound and its synthetic method and anti-true Application in bacterium and antibacterial medicines.
2- substitution -3- azacyclo- Thiochromone compounds involved in the present invention, its chemical constitution are as follows：
R3One kind in five yuan of nitrogen azoles rings of such as formula (II)：
Wherein：J, K, L are separately selected from hydrogen, C1-C3Alkyl；
R2Selected from hydrogen,- O-Z or C1-C3Alkyl-substituted penta azacyclo；
Wherein, Y is selected from hydrogen；C1-C6Alkyl；Benzyl；Containing in trifluoromethyl, trifluoromethoxy, nitro, halogen, cyano group Five yuan or hexa-atomic aromatic ring of one or more substituents；
Y ' is selected from hydrogen；C1-C6Alkyl；
Z is selected from hydrogen；C1-C6Alkyl；Benzyl；Containing one in trifluoromethyl, trifluoromethoxy, nitro, halogen, cyano group Or five yuan or hexa-atomic aromatic ring of multiple substituents；
R4、R5、R7Separately selected from hydrogen, fluorine, chlorine, bromine or iodine；
R6Selected from hydrogen, fluorine, chlorine, bromine, iodine, C1-C6Oxyl, C1-C6Hydrocarbon amino, C1-C6Alkyl, phenoxy group, by 1 Individual or multiple C1-C6The phenoxy group of oxyl substitution；
The synthetic method of formula (I) compound, it is that compound (III) is dissolved in organic solvent, is reacted with carbon disulfide, warp Condensation, after cyclization with C1-C6Halohydrocarbons reaction generation compound (V), oxidized dose of compound (V) oxidation generation compound (VI), then under the conditions of alkali compounds and R2H reacts, and obtains solid product 2- substitution -3- azacyclo- thiochromone class chemical combination Thing；
The structural formula of the compound (III) is as follows：
The structural formula of the compound (V) is as follows：
The structural formula of the compound (VI) is as follows：
Wherein, X represents F or Cl；
R2、R3、R4、R5、R6、R7The same formula of definition (I)；
R8Selected from C1-C6Alkyl；
The organic solvent be selected from DMF, DMA, dimethyl sulfoxide, dioxane, At least one of acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, tert-butyl alcohol.It is preferred that DMF, diformazan are sub- Sulfone.
The oxidant is selected from manganese dioxide, potassium permanganate, potassium bichromate, hydrogen peroxide, benzoyl hydroperoxide, m-chloro peroxide At least one of benzoic acid, magnesium monoperoxyphthalate or Peracetic acid.It is preferred that hydrogen peroxide, metachloroperbenzoic acid.
The alkali compounds is selected from alkali carbonate, alkali metal hydroxide, alkali metal acetate or triethylamine, two In ethyl isopropylamine, N- methyl piperidines, N-ethylpiperidine, N-methylmorpholine, N-ethylmorpholine, pyridine, 4- picolines extremely Few one kind.It is preferred that sodium hydroxide, potassium hydroxide, potassium carbonate, cesium carbonate.
The reaction can use each step product to be directly entered the one-step synthesis of reaction in next step without isolation or incite somebody to action Often walk reaction product isolated and purified after enter in next step reaction step synthesis.
The synthetic method of the present invention is a kind of universal method, is suitable for synthesizing thiochromone compound and its derivative, to virtue A variety of functional groups on ring have high tolerance, therefore in fact to the substituent in Thiochromone compound and its derivative There is no particular restriction for number and species.
Formula (I) compound of the present invention also includes its salt allowed on pharmaceutics.
The present invention provides the 2- substitutions -3- azacyclo-s Thiochromone compound and is preparing the people for the treatment of fungal infection disease With the application in medicine or medicine for animal.
In the medicine in addition to containing active component 2- substitution -3- azacyclo- Thiochromone compounds, also contain and medicine Upper acceptable carrier, auxiliary agent and/or diluent, form composition.
The formulation of the medicine is solution, creme, suppository, paste or solution.
The present invention also provides the 2- substitutions -3- azacyclo-s Thiochromone compound and answered as agriculture and horticultural bactericides With.
In the bactericide in addition to containing active component 2- substitution -3- azacyclo- Thiochromone compounds, also contain and medicine Acceptable carrier, auxiliary agent and/or diluent on thing, form composition.
By determining minimum inhibitory concentration MIC (i.e. compound can suppress to test the concentration of microorganism growth), to the present invention The antifungal activity of 2- substitution -3- azacyclo- Thiochromone compounds has carried out in-vitro evaluation.Experiment confirms that 2- of the present invention takes Generation -3- azacyclo- Thiochromone compounds have broad-spectrum antifungal activity, internal in human body and animal (particularly mammal) It with pharmacological activity, can mix with the acceptable diluent or carrier of common chemotherapy, or with other excipient, be made molten The formulations such as liquid, creme, suppository, ointment, solution, partial smearing use is carried out in the form of medicine, is had for fungal infection disease The effect of obvious.Except for preparing antimycotic people's use or animal antifungal beyond the region of objective existence, 2- substitutions -3- azacyclo-s of the present invention Thiochromone compound can be also used for agricultural and gardening bactericide, to various phytopathogen disease such as rice blast, Barley and the powder mildew of wheat and the powder mildew of other various host plants (such as cucumber, apple, grape), the rust of wheat, swallow The hat rust of wheat and the rust of other various hosts, the preventing and treating that the pathogenicities of the late blight of tomato and other host plants is rotted etc. It is highly effective.
Embodiment
The synthetic method of the present invention is illustrated below by specific embodiment.It should be noted that given here retouch The embodiment just for the sake of the description present invention with embodiment is stated, technical staff is easier to understand the present invention, they It is not intended to limit the scope of the present invention.
Embodiment 1, the synthetically prepared reaction equation of Formula V 1 are as follows：
Preparation process is as follows：
1- (2,4- bis- chloro- 5- fluorophenyls) -2- (4-methylpyrazole -1- bases) ethyl ketone 18.4mmol is added in single-necked flask, DMSO30mL, NaOH 43mmol, 40 DEG C are warming up under stirring, CS is added dropwise at this temperature222.8mmol 5mL DMSO's is molten Liquid.Drop finishes, 40 DEG C of stirring reactions of temperature control.Reaction is finished, and is cooled to room temperature, and iodoethane 25.6mmol 10mL DMSO solutions are added dropwise, Drop finishes, and room temperature reaction to reaction is finished, and reaction solution is stirred down and poured into 50mL frozen water, has a large amount of solids to separate out, and is collected by filtration solid Body, recrystallize in ethanol, obtain the fluoro- 7 chlorine thiochromones of formula (V1) product 2- ethylmercapto groups -3- (4-methylpyrazole -1- bases) -6- -- 14.0mmol, yield 76%.
1H NMR (300MHz, DMSO) δ=8.48 (d, 1H), 8.16 (d, 1H), 7.54 (d, 2H), 3.26 (q, 2H), 2.12 (s, 3H), 1.33 (t, 3H)
2~embodiment of embodiment 7：The preparation of formula (V) Thiochromone compound
Using (III) compound as raw material, preparing product formula (V) compound, (target product is formula (V2)~(V7) in table 1 Each compound), for preparation process with embodiment 1, reaction equation is as follows：
In 2~embodiment of embodiment 7, each group selection of product formula (V) Thiochromone compound and preparation reagent and inspection Survey data and be listed in table 1.
Embodiment 8：The synthetically prepared reaction equation of Formula IV 1 is as follows：
Preparation process is as follows：
Into 100mL single-necked flasks, the fluoro- 7 chlorine thiochromones of 2- ethylmercapto groups -3- (4-methylpyrazole -1- bases) -6- are sequentially added 10mmol, acetic acid 20mL, 65 DEG C are heated to, 30% H is added dropwise2O212mmol stirring reactions 6 hours, add sodium sulfite extraction and go out, It is evaporated under reduced pressure and removes solvent acetic acid, is then extracted with 50mL dichloromethane and 50mL water, take dichloromethane layer, be washed twice with water (50mL × 2), organic layer is reclaimed, is evaporated under reduced pressure to formula (VI1) product 2- second sulfinyls -3- (4-methylpyrazole -1- bases) -6- Fluoro- 7 chlorine thiochromone 8.9mmol, yield 89%.
1H NMR (500MHz, DMSO) δ 8.69 (d, 1H), 8.24 (d, 1H), 7.97 (s, 1H), 7.64 (s, 1H), 3.67- 3.69 (m, 1H), 2.76-2.79 (m, 1H), 2.14 (s, 3H), 1.25-1.31 (m, 3H)
9~embodiment of embodiment 14：The preparation of formula (VI) Thiochromone compound
Respectively using (V2~V7) compound as raw material, preparing product formula (VI2~VI7) compound, (preparation process is the same as implementation Example 8, reaction equation is as follows：
In 9~embodiment of embodiment 14, each group selection of product formula (VI2~VI7) Thiochromone compound and preparation are used Reagent and detection data are listed in table 2.
Table 2
Embodiment 15：The synthetically prepared reaction of formula (I1) is as follows：
Preparation process is as follows：
Into 100mL single-necked flasks, the fluoro- 7 chlorine sulphur of 2- second sulfinyls -3- (4-methylpyrazole -1- bases) -6- is sequentially added Chromone 1mmol, K2CO32.5mmol and 5mL DMF, under room temperature condition, magnetic agitation is opened, weighs 1.5mmol diformazan aqueous amine Solution, it is slowly dropped at room temperature in reaction solution.Question response is finished, and is extracted with 20mL dichloromethane and 20mL water, takes dichloromethane Layer, is washed twice with water (20mL × 2), and recovery organic layer is evaporated under reduced pressure, and obtains formula (I1) product 2- dimethylamino -3- (4- methyl Pyrazol-1-yl) the fluoro- 7 chlorine thiochromone 0.82mmol of -6-, yield 82%.
1HNMR (500MHz, DMSO) δ 8.25 (d, 1H), 8.03 (d, 1H), 7.53 (s, 1H), 7.45 (s, 1H), 2.83 (s, 6H), 2.11 (s, 3H)
16~embodiment of embodiment 23：The preparation of formula (I) Thiochromone compound
Respectively using (VI) compound as raw material, prepare product formula (I) compound (target product be table 1 in formula (I2)~ (I9) each compound), for preparation process with embodiment 15, reaction equation is as follows：
In 16~embodiment of embodiment 23, the selection of each group of product formula (I) Thiochromone compound and preparations reagent with Detection data are listed in table 3.
Table 3
Embodiment 24：Extracorporeal antifungal activity is tested
1st, experiment bacterial strain
Candida parapsilosis, sporothrix, saccharomyces cerevisiae Aspergillus, Candida albicans, Candida glabrata, tropical beads Bacterium, Trichophyton rubrum, Penicillium notatum, Trichophyton verrucosum, Trichophyton violaceum, neogenesis cryptococcus, gram Rou Shi candida albicans, Epidermophvton tinea Bacterium, trichophyton gypseum.
2nd, reagent and material
Experiment material：
Improve Martin's culture medium, 96 well culture plates, DMSO
Control drug：Fluconazole
3rd, experimental method
(1) preparation of antibacterial decoction
Test medicine is dissolved with DMSO respectively, 25.6g/L solution is made into, is saved backup in less than -20 DEG C.Before experiment The tested decoction of deepfreeze is taken out, melted in 35 DEG C of insulating boxs, it is standby with 10 times of RPMI1640 dilutions.
(2) preparation of inoculation liquid
The tested beads bacterial strain of brother (Candida parapsilosis, Candida albicans, Candida glabrata, Candida tropicalis) is in improvement horse Transferred species on fourth culture medium, suspension is made with the Sterile Saline that mass fraction is 0.85% in it.Spore is counted with blood cell counting plate Son, bacteria containing amount is adjusted, it is 1 × 10 to make colony forming unit6~5 × 106CFU/mL.During inoculation with RPMI-1640 nutrient solutions by its After 200 times of dilution, then 10 times are diluted, CFU values are adjusted to 0.5 × 103~6.0 × 103CFU/mL, it is standby.
(3) prepared by MIC plates
Under sterile working, add the μ L of RPMI-1640 nutrient solutions 100 in No. 1 hole of 96 hole polyethylene boards of sterilizing, as sky White control.No. 2 hole adds the μ L of bacterium solution 190, and 3-12 holes add the μ L of bacterium solution 100 configured.Then 10 μ L are added in No. 2 holes Tested decoction, by the concentration in 10 grades of doubling dilution 2-11 holes, the ultimate density for making each hole is 128,64,32,16,8,4,2,1, 0.5,0.25mg/L, No. 12 hole is not added with tested decoction as growth control.35 DEG C of normal airs are placed in after each MIC plates are closed to incubate In case, full 24h judged results are incubated.
(4) result judges
The OD values in each hole are surveyed in 620nm with enzyme micro-plate reader, the least concentration for declining more than 80% using OD values is used as MIC Value.＞ 128mg/L are calculated as when MIC value is higher than 128mg/L；≤ 0.25mg/L is calculated as when MIC value is less than 0.25mg/L.
(5) repeated observation and statistics
Above-mentioned experiment needs at least in triplicate, when occurring that MIC value is single to jump hole, is then recorded as the suppression bacterium of maximum Concentration, when two or more, which occurs, in MIC value jumps hole, then re-start experiment.
4th, antimycotic sensitivity tests result
Determined and found by preliminary MIC, test-compound has broad-spectrum antifungal activity, wherein embodiment (15)~reality It is more notable to apply the Thiochromone compound suppression fungi activity of example (24), 10mg/ is respectively less than to the MIC value of above strain subject L。

Claims (8)

  1. It is 1. a kind of as the 2- substitution -3- azacyclo- Thiochromone compounds of formula (I), its chemical constitution are as follows：
    R3One kind in five yuan of nitrogen azoles rings of such as formula (II)：
    Wherein：J, K, L are separately selected from hydrogen, C1-C3Alkyl；
    R2Selected from hydrogen,- O-Z or C1-C3Alkyl-substituted penta azacyclo；
    Wherein, Y is selected from hydrogen；C1-C6Alkyl；Benzyl；Containing one in trifluoromethyl, trifluoromethoxy, nitro, halogen, cyano group Or five yuan or hexa-atomic aromatic ring of multiple substituents；
    Y ' is selected from hydrogen；C1-C6Alkyl；
    Z is selected from hydrogen；C1-C6Alkyl；Benzyl；Containing one in trifluoromethyl, trifluoromethoxy, nitro, halogen, cyano group or more Five yuan or hexa-atomic aromatic ring of individual substituent；
    R4、R5、R7Separately selected from hydrogen, fluorine, chlorine, bromine or iodine；
    R6Selected from hydrogen, fluorine, chlorine, bromine, iodine, C1-C6Oxyl, C1-C6Hydrocarbon amino, C1-C6Alkyl, phenoxy group, by 1 or Multiple C1-C6The phenoxy group of oxyl substitution.
  2. 2. compound according to claim 1, its feature compound includes its salt allowed on galenic pharmacy.
  3. 3. a kind of synthetic method of the formula of claim 1 (I) compound, it is characterized in that, compound (III) is dissolved in organic solvent In, reacted with carbon disulfide, through condensation, after cyclization with C1-C6Halohydrocarbons reaction generation compound (V), compound (V) is through oxygen Agent oxidation generation compound (VI), then reacted under the conditions of alkali compounds with R2H, obtain solid product 2- substitutions -3- Azacyclo- Thiochromone compound；
    The structural formula of the compound (III) is as follows：
    The structural formula of the compound (V) is as follows：
    The structural formula of the compound (VI) is as follows：
    Wherein, X represents F or Cl；
    R2、R3、R4、R5、R6、R7The same formula of definition (I)；
    R8Selected from C1-C6Alkyl.
  4. 4. synthetic method according to claim 3, it is characterized in that the organic solvent is selected from DMF, N, In N- dimethyl acetamides, dimethyl sulfoxide, dioxane, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, the tert-butyl alcohol extremely Few one kind；The oxidant is selected from manganese dioxide, potassium permanganate, potassium bichromate, hydrogen peroxide, benzoyl hydroperoxide, m-chloro peroxide At least one of benzoic acid, magnesium monoperoxyphthalate or Peracetic acid；The alkali compounds is selected from alkali metal carbonic acid Salt, alkali metal hydroxide, alkali metal acetate or triethylamine, diethylisopropylamide, N- methyl piperidines, N-ethylpiperidine, N- Methyl morpholine, N-ethylmorpholine,；At least one of pyridine, 4- picolines.
  5. 5. according to the synthetic method described in claim 3,4, it is characterized in that the organic solvent be selected from DMF, Dimethyl sulfoxide；The oxidant is selected from hydrogen peroxide, metachloroperbenzoic acid；The alkali compounds is selected from sodium hydroxide, hydrogen Potassium oxide, potassium carbonate, cesium carbonate.
  6. 6. according to the synthetic method described in claim 3-5, it is characterized in that often step reaction product is directly entered without isolation The one-step synthesis of reaction or enter the substep of reaction in next step after the product that every step is reacted is isolated and purified in next step Synthetic method.
  7. 7. 2- substitutions -3- azacyclo-s Thiochromone compound described in a kind of claim 1 is answered as agriculture and horticultural bactericides With.
  8. 8. application according to claim 7, contain active component 2- substitution -3- azepines it is characterized in that being removed in the bactericide Outside epithio chromone compounds, also containing pharmaceutically acceptable carrier, auxiliary agent and/or diluent, composition is formed.
CN201610450799.3A 2016-06-17 2016-06-17 A kind of 23 azacyclo- Thiochromone compounds of substitution and its synthetic method and the application in antifungal drug Pending CN107513059A (en)

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Cited By (1)

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CN109280051A (en) * 2018-09-20 2019-01-29 南京工业大学 A kind of preparation of chromone compounds and its application in dye-sensitized solar cells

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CN1147514A (en) * 1996-06-14 1997-04-16 沈阳药科大学 Thiochrome ketones as antifungal agent
CN1246118A (en) * 1997-01-28 2000-03-01 大塚化学株式会社 Chromone derivatives and bactericidal and herbicidal agent containing the same as active ingredient
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