CN114685495A - N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, antibacterial, herbicidal and anticancer effects, and preparation and application thereof - Google Patents

N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, antibacterial, herbicidal and anticancer effects, and preparation and application thereof Download PDF

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CN114685495A
CN114685495A CN202210330025.2A CN202210330025A CN114685495A CN 114685495 A CN114685495 A CN 114685495A CN 202210330025 A CN202210330025 A CN 202210330025A CN 114685495 A CN114685495 A CN 114685495A
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difluoromethyl
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汤日元
董丽
郭雪莹
黄子豪
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South China Agricultural University
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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Abstract

The invention provides an N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects, and a preparation method and an application thereof. Belongs to the field of medicine molecules. The N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers has a structure shown in a general formula (A). The N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers shows good biological activity on pests in agriculture, forestry and other fields, plant pathogenic bacteria in agriculture, weeds and harmful plants in the agricultural field; the N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects also have an inhibiting effect on human ovarian cancer cells A2780 and human breast cancer cells BT-20.

Description

N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, antibacterial, herbicidal and anticancer effects, and preparation and application thereof
Technical Field
The invention belongs to the field of drug molecules, and particularly relates to an N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects, and a preparation method and an application thereof.
Background
The prior inventor firstly develops a series of N-difluoroalkyl azole sulfur (selenium) urea derivatives and preparation methods and applications thereof (Chinese patent: ZL201810648408.8 an azole sulfur (selenium) ketone derivative, a preparation method and applications thereof; Chinese patent: ZL201811452050.8 an N-difluoromethyl azole sulfur (selenium) urea derivative and a preparation method thereof; Chinese patent application: CN202010743473.6 benzimidazolone derivatives or agriculturally and pharmaceutically acceptable salts and applications thereof; Chinese patent application: CN202011222204.1N-difluoromethyl azole selenium urea derivatives or agriculturally and pharmaceutically acceptable salts and applications thereof), wherein the N-difluoroalkyl azole sulfur (selenium) urea comprises N-difluoroalkyl benzimidazole sulfur (selenium) urea, N-difluoroalkyl imidazole sulfur (selenium) urea, N-difluoroalkyl triazole sulfur (selenium) urea and the like. Biological activity research shows that N-difluoromethyl benzimidazole selenouride and N-difluoromethyl imidazole selenouride compounds have insecticidal activity of different degrees on agricultural pests such as diamond back moth, meloidogyne incognita, prodenia litura and the like, but the total insecticidal activity is not ideal enough. The N-difluoromethyl benzimidazole selenourea and the N-difluoromethyl imidazole selenourea compounds have no obvious biological activity on plant germs and weeds at the concentration of 100 mg/L. Selenium is an important microelement essential to animals and plants, and the organic selenium compound is reasonably designed and prepared to be absorbed and transformed by the animals and plants, so that the immunity and the stress resistance of the animals and plants can be effectively improved. The inventor hopes to create an organic selenium molecule with multiple biological functions and high activity by means of the functional characteristics of selenium and combining the electronic characteristics of a heterocyclic skeleton, so that the organic selenium molecule can be better applied to agricultural production, and the problems that the prior N-difluoromethyl azole selenourea has single biological function and unsatisfactory activity are solved.
Disclosure of Invention
The invention aims to provide the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers. The N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing, inhibiting bacteria, weeding and resisting cancer is an N-difluoromethyl dinitrogen heterocyclic selenourea compound which can control various agricultural and forestry pests, sanitary pests, various plant pathogenic bacteria, various weeds and inhibit human cancer cells. The insecticidal activity of the N-difluoromethyl dinitrogen heterocyclic selenourea compound developed by the invention is obviously superior to that of N-difluoromethyl benzimidazole selenourea and N-difluoromethyl imidazole selenourea developed by the inventor in the earlier stage; particularly, the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects shows excellent bacteriostatic activity; it is worth pointing out that the N-difluoromethyl benzimidazole selenourea and the N-difluoromethyl benzimidazole selenourea compounds created by the inventor in the prior art do not have the functions of bacteriostasis and weeding under the same concentration (50 ppm). The N-difluoromethyl dinitrogen heterocyclic selenourea compound developed by the invention has biological functions of killing insects, inhibiting bacteria, weeding, resisting cancers and the like.
The invention also aims to provide a preparation method of the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects.
The invention also aims to provide application of the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects.
The purpose of the invention is realized by the following technical scheme:
an N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects has a structure shown as a general formula (A):
Figure BDA0003574916350000021
the preferred technical scheme of the invention is as follows:
x in the general formula (A) is selected from any one of C, N atoms.
In the general formula, the heterocyclic ring in the ring phase with the selenourea is a nitrogen-containing heterocyclic ring; including but not limited to any of the following rings: a pyrazine ring, a pyridine ring, a pyrimidine ring, a quinoline ring, a pyridazine ring, an isoquinoline ring, a triazine ring, an imidazole ring, an oxazole ring, a pyrazole ring, an isoxazole ring, a thiazole ring, a purine ring, an isothiazole ring, a pteridine ring, a piperidine ring, a tetrahydropyrazine ring.
When X is N, no R1Substituent, R2The substituent group on any position or any atom on the heterocycle can be mono-substituted, same or different groups of bi-substituted and tri-substituted. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C12An alkyl group;
when X ═ C, R1Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C12An alkyl group; r2The substituent group on any position or any atom on the heterocycle can be mono-substituted, same or different groups of bi-substituted and tri-substituted. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C12An alkyl group.
The further preferable technical scheme of the invention is as follows:
x in the general formula (A) is selected from any one of C, N atoms.
In the general formula, the heterocyclic ring in the ring phase with the selenourea is a nitrogen-containing heterocyclic ring; including but not limited to any of the following rings: a pyrazine ring, a pyridine ring, a pyrimidine ring, a quinoline ring, a pyridazine ring, an isoquinoline ring, a triazine ring, an imidazole ring, an oxazole ring, a pyrazole ring, an isoxazole ring, a thiazole ring, a purine ring, an isothiazole ring, a pteridine ring, a piperidine ring, a tetrahydropyrazine ring.
When X is N, no R1Substituent, R2The substituent group on any position or any atom on the heterocycle can be mono-substituted, same or different groups of bi-substituted and tri-substituted. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group;
when X ═ C, R1Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group; r2Is a substituent at any position or atom on the heterocycle, and can be mono-substituted, di-substituted and tri-substituted by the same or different groups. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group.
Still further preferred technical scheme of the invention is as follows:
x in the general formula (A) is selected from any one of C, N atoms.
In the general formula, the heterocyclic ring in the ring phase with the selenourea is a nitrogen-containing heterocyclic ring; including but not limited to any of the following rings: a pyrazine ring, a pyridine ring, a pyrimidine ring, a quinoline ring, a pyridazine ring, an isoquinoline ring, a triazine ring, an imidazole ring, an oxazole ring, a pyrazole ring, an isoxazole ring, a thiazole ring, a purine ring, an isothiazole ring, a pteridine ring, a piperidine ring, a tetrahydropyrazine ring.
When X is N, no R1Substituent, R2Is at any position or at any position on the heterocycleThe substituent on the meaning atom can be mono-substituted, same or double-substituted and tri-substituted of different groups. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group;
when X ═ C, R1Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group; r2Is a substituent at any position or atom on the heterocycle, and can be mono-substituted, di-substituted and tri-substituted by the same or different groups. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group.
The invention further preferably adopts the technical scheme that:
x in the general formula (A) is selected from any one of C, N atoms.
In the general formula, the heterocyclic ring in the ring phase with the selenourea is a nitrogen-containing heterocyclic ring; including but not limited to any of the following rings: a pyrazine ring, a pyridine ring, a pyrimidine ring, a quinoline ring, a pyridazine ring, an isoquinoline ring, a triazine ring, an imidazole ring, an oxazole ring, a pyrazole ring, an isoxazole ring, a thiazole ring, a purine ring, an isothiazole ring, a pteridine ring, a piperidine ring, or a tetrahydropyrazine ring.
When X is N, no R1Substituent, R2The substituent group on any position or any atom on the heterocycle can be mono-substituted, same or different groups of bi-substituted and tri-substituted. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C4An alkyl group.
When X ═ C, R1Selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C4An alkyl group; r2The substituent group on any position or any atom on the heterocycle can be mono-substituted, same or different groups of bi-substituted and tri-substituted. Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C4An alkyl group.
The N-difluoromethyl dinitrogen heterocyclic selenourea compounds with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers comprise but are not limited to compounds D-1-D-27, and the structures of the compounds are shown as follows:
Figure BDA0003574916350000041
the pharmaceutically acceptable salt of the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of disinsection, bacteriostasis, weeding and cancer resistance is formed by the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of disinsection, bacteriostasis, weeding and cancer resistance and acid; the acid includes, but is not limited to, at least one of hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, fumaric acid, sorbic acid, malic acid, and citric acid.
The preparation method of the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancer comprises the following steps:
dissolving dinitro heterocyclic compound, selenium powder and alkali with organic solvent, adding 2-bromo-2, 2-difluoroacetate BrCF2CO2Et, sealing, heating for reaction, cooling, extracting, drying and purifying to obtain the productN-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects; the reaction path is shown as formula (1):
Figure BDA0003574916350000051
the preparation method of the N-difluoromethyl dinitro heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancer comprises the following steps:
the base includes, but is not limited to, at least one of potassium carbonate and potassium tert-butoxide.
The dinitrogen heterocyclic compound, the selenium powder, the 2-bromo-2, 2-difluoroacetate and the alkali are preferably calculated according to a molar ratio of 0.10-0.30: 0.30-0.50: 0.4-0.6: 0.30-0.50; more preferably calculated as 0.20:0.40:0.5: 0.40.
The organic solvent includes but is not limited to at least one of N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, 1, 4-dioxane and acetone; more preferably acetonitrile.
The heating reaction conditions are preferably as follows: stirring and reacting in an oil bath kettle at the temperature of 40-120 ℃; more preferably: stirring and reacting for 24 hours in an oil bath kettle at 100 ℃.
The extraction reagent is preferably ethyl acetate.
The dried reagent is preferably anhydrous Na2SO4。
The purification is preferably carried out by column chromatography; when column chromatography is used for purification, the eluent used is preferably petroleum ether and ethyl acetate.
The N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers shows control effect on pests, plant pathogenic bacteria, agricultural weeds and human cancer cells in the technical field of agriculture. Therefore, another technical scheme of the invention relates to the application of the N-difluoromethyl dinitrogen heterocyclic selenourea compound or the agriculturally and pharmaceutically acceptable salt thereof with the functions of disinsection, bacteriostasis, weeding and cancer resistance in pesticides, bactericides, herbicides and preparations for treating and/or preventing cancers, namely the application of the N-difluoromethyl dinitrogen heterocyclic selenourea compound or the pharmaceutically acceptable salt thereof with the functions of disinsection, bacteriostasis, weeding and cancer resistance in preparing the medicines for disinsection, sterilization, weeding and cancer resistance.
Such insects include, but are not limited to, agricultural and/or forestry insects; the agricultural and/or forestry insects include, but are not limited to, at least one of Lepidoptera (Lepidoptera) insects, Coleoptera (Coleoptera) insects, Hemiptera (Hemiptera) insects, homoptera (Hcmoptera) insects, Orthoptera (Orthoptera) insects, Hymenoptera (Hymenoptera) insects, blattaria insects, Diptera (Diptera) insects, and plant parasitic nematodes.
The lepidopteran (Lepidoptera) insects include, but are not limited to: plutella xylostella (Plutella xylostella), Spodoptera frugiperda (Spodoptera frugiperda), Spodoptera exigua (s.exigua), Spodoptera litura (s.litura), gypsy moth (Lymantria dispar), trichosanthis tenuis (malacospora neosticea), Diaphania punctata (Diaphania persicae), gloea gigantea (Clania variegata), yellow spiny moth (cnidocapa flaccus), masson pine moth (Dendrolimus puncatus), archaea viridis (Orgyia antica), populus heteroptera (Paranthrene), Chilo suppressalis (Chilo supressalis), Ostrinia nubilalis (Ostrinia nubilalis), Ostrinia punctata (Hestia), Ostrinia punctata (Ostrinia nubilalis), Ostrinia nubilalis (Ostrinia nubilalis), Ostrinia nubila nubilalis (Ostrinia nubila, Ostrinia nubila, Ostrinia nubila litura (Ostrinia litura), Ostrinia nubila litura), Ostrinia nubila litura (Ostrinia nubila, Ostrinia litura), Ostrinia nubila (Ostrinia nubila (Ostrinia nubila, Ostrinia nubila (Ostrinia nubila, Ostrinia (Ostrinia nubila, Ostrinia litura), and Ostrinia litura (Ostrinia nubila (Ostrinia nubila, Ostrinia nubila (Ostrinia, Ostrinia nubila, Ostrinia nubila, and Ostrinia nubila (Ostrinia nubila, Ostrinia nubila (Ostrinia, Ostrinia nubila, Ostrinia, and Ostrinia nubila, Ostrinia nubila, and Ostrinia nubila, Ostrinia nubila, and Ostrinia nubila, Ostrinia nubila, Ostrinia nubila, and Ostrinia nubila (e).
The coleopteran (Coleoptera) insects include, but are not limited to: elephant of maize (Sitophilus zeamais), Tribophytes castanea (Tribolium castaneum), Harpagophyta japonica (Henospora virginiana), Harpagophyta dyphyllum (H.spaciana), Elaeagnus minutissima (Agriotes fusciparus), Rhynchophorus cantoniensis (Ancmala cupripipes), Rhynchophorus tetragonolobus (Popilia quadrata), Tolypocladium arborvita (Monolepis hieroglyphica), Sonchus arvensis (Monochamus altatus), Rhus oryzae (Echinocnemus squamosus), Ascophyllum robusta (Basipronota biosignata), Ascophyllum chinense (Anoplophora chinensis), Morus alba (Apriparia marina mariger), Abrus umbiliciformis minor scholar (Soclepiay) and Verticillium vularia (Agileria spp).
The Hemiptera (Hemiptera) insects include but are not limited to: at least one of Nezara viridula, Piperus brevicaulis (Poecilomis nashi), Piperus oryzophilus (Nezara viridula), Piperus europaeus (Poecilocoris latius), Piperus oryzae (Cletus punctiger), Piperus kawachii (Dimorphpterus japonica) and Piperus gossypii (Dysdercus cingulatus).
The homoptera (hcmpoptera) insects include, but are not limited to: at least one of Nephotettix cincticeps, arrowhead scales (Unaspis yanonensis), Myzus persicae (Myzus persicae), Aphis gossypii (Aphis gossypii), Bemisia tabaci (Bemisia tabaci), Laodelphax striatellus (Laodelphax striatellus), Nilaparvata lugens (Nilaparvata lugens) and Sogatella furcifera.
The Orthoptera (Orthoptera) insects include, but are not limited to: at least one of Gryllotalpa africana and locusta migratoria asiatica (Locus migratoria).
The Hymenoptera (Hymenoptera) insects include, but are not limited to: at least one of Solenopsis invicta and Vespa mandarinia.
Insects of the blattaria include, but are not limited to: at least one of German cockroach (Blattella germanica), American cockroach (Periplaneta americana), and Copottermes formosamus.
The Diptera (Diptera) insects include, but are not limited to: at least one of Musca dcmestica, Aedes aegypti (Aedes aegypti), seed fly (Delia platura), Culex (Culex fatigans), and Anopheles sinensis (Anopheles sinensis).
The plant parasitic nematodes include, but are not limited to: at least one of root-knot nematode, root-rot nematode, aphelenchoides besseyi and bursaphelenchus xylophilus; the root knot nematode includes, but is not limited to, Meloidogyne incognita (Kofold & White) Chitwood).
The insects also include pests that are harmful to the health of animals; such pests that are harmful to the health of animals include, but are not limited to: at least one of Boophilus microplus, Haemaphysalis longicornis, Hyalhyalomma glaucosum, Dermatophagus bovis (Hypoderma bovis), Fasciola hepatica (Fasciola hepatica), Monizzia beli (Moniezia blanchard), Protozoa (Trypanosoma enansi) and Babesia bigemina.
The bacteria include, but are not limited to, at least one of Deuteromycotina, Basidiomycotina, Ascomycotina, Hymenomycotina, and Trichuris subphylum.
The bacteria include but are not limited to the following bacteria of pathogenic origin: downy mildew, white rust, damping-off, soft rot, epidemic disease, late blight, root rot, damping-off, verticillium wilt, scab, gray mold, brown spot, black spot, spot blight, early blight, ring spot, leaf blight, stem rot, basidioidomycosis, smut, ascomycete, sclerotinia, scab and clubroot.
The downy mildew includes but is not limited to at least one of cucumber downy mildew, rape downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, towel gourd downy mildew, wax gourd downy mildew, melon downy mildew, Chinese cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew and onion downy mildew.
The white rust fungus includes but is not limited to at least one of white rust fungus of rape and white rust fungus of cabbage class.
The damping-off disease comprises but is not limited to at least one of rape damping-off disease, tobacco damping-off disease, tomato damping-off disease, pepper damping-off disease, eggplant damping-off disease, cucumber damping-off disease and cotton seedling damping-off disease.
The cotton rot includes but is not limited to at least one of pepper cotton rot, towel gourd cotton rot and wax gourd cotton rot.
The epidemic disease includes but is not limited to at least one of a broad bean epidemic disease, a cucumber epidemic disease, a wax gourd epidemic disease, a watermelon epidemic disease, a melon epidemic disease, a pepper epidemic disease, a leek epidemic disease, a garlic epidemic disease and a cotton epidemic disease.
The late blight includes but is not limited to at least one of potato late blight and tomato late blight.
The root rot disease includes but is not limited to at least one of pepper root rot, eggplant root rot, kidney bean root rot, cucumber root rot, bitter gourd root rot, cotton root rot and broad bean root rot.
The damping off includes but is not limited to at least one of cotton seedling damping off, sesame damping off, pepper damping off, cucumber damping off and cabbage damping off.
The verticillium wilt comprises but is not limited to at least one of cotton verticillium wilt, sunflower verticillium wilt, tomato verticillium wilt, pepper verticillium wilt and eggplant verticillium wilt.
The scab includes but is not limited to at least one of cucurbita pepo scab, wax gourd scab and melon scab.
The gray mold includes but is not limited to at least one of boll black gray mold, kenaf gray mold, tomato gray mold, pepper gray mold, bean gray mold, cucumber gray mold, soybean gray mold, kiwi fruit gray mold, grass duck gray mold, leek gray mold and spinach gray mold.
The brown spot includes, but is not limited to, at least one of cotton brown spot, jute brown spot, sugar beet brown spot, peanut brown spot, pepper brown spot, wax gourd brown spot, soybean brown spot, sunflower brown spot, pea brown spot and broad bean brown spot.
The black spot comprises but is not limited to at least one of pseudoblack spot of flax, black spot of rape, black spot of sesame, black spot of sunflower, black spot of castor-oil plant, black spot of tomato, black spot of hot pepper, black spot of eggplant, black spot of kidney bean, black spot of cucumber, black spot of celery, black spot of carrot, black spot of apple and black spot of peanut.
The spot blight disease comprises but is not limited to at least one of tomato spot blight disease, pepper spot blight disease and celery spot blight disease.
The early blight includes but is not limited to at least one of tomato early blight, pepper early blight, eggplant early blight, potato early blight and celery early blight.
The ring spot includes but is not limited to at least one of soybean ring spot, sesame ring spot and bean ring spot.
The leaf blight includes but is not limited to at least one of sesame leaf blight, sunflower leaf blight, watermelon leaf blight and melon leaf blight.
The basal stem rot disease comprises but is not limited to at least one of tomato basal stem rot disease and bean basal stem rot disease.
The basidiomycetous diseases include but are not limited to rust; the rust includes, but is not limited to, at least one of wheat stripe rust, wheat straw rust, wheat leaf rust, peanut rust, sunflower rust, red deer rust, leek rust, scallion rust, chestnut rust and soybean rust.
The smut disease includes, but is not limited to, at least one of corn head smut, corn smut, sorghum head smut, sorghum panicle disease, sorghum hard smut, sorghum column smut, millet black panicle disease, sugarcane black panicle disease and kidney bean rust disease.
The ascomycetes diseases include but are not limited to powdery mildew; the powdery mildew includes but is not limited to at least one of wheat powdery mildew, Shancai powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, towel gourd powdery mildew, pumpkin powdery mildew, wax gourd powdery mildew, melon powdery mildew, grape powdery mildew and broad bean powdery mildew.
The sclerotinia rot includes but is not limited to at least one of flax sclerotinia rot, rape sclerotinia rot, soybean sclerotinia rot, peanut sclerotinia rot, tobacco sclerotinia rot, pepper sclerotinia rot, eggplant sclerotinia rot, bean sclerotinia rot, pea sclerotinia rot, cucumber sclerotinia rot, bitter gourd sclerotinia rot, wax gourd sclerotinia rot, watermelon sclerotinia rot and celery sclerotinia rot.
The scab includes but is not limited to at least one of apple scab and pear scab.
The clubroot disease comprises but is not limited to at least one of clubroot disease of cabbage, clubroot disease of cauliflower, clubroot disease of radix isatidis, clubroot disease of mustard, clubroot disease of radish, clubroot disease of turnip and clubroot disease of rape.
The bacteria also comprise the following bacteria with pathogenic sources: corn leaf spot, red ramie waist break, rice blast, sheath blight, sugarcane eye spot, peanut crown rot, soybean stem rot, soybean black spot, melon northern leaf spot, peanut net spot, tea red leaf spot, pepper white spot, wax gourd leaf spot, sprout black rot, spinach heart rot, red ramie leaf mold, red ramie spot, jute stem spot, soybean purple spot, sesame leaf spot, castor gray spot, tea brown leaf spot, eggplant brown spot, red bean spot, bitter gourd white spot, watermelon spot, jute root rot, sunflower root stem rot, vegetable bean carbon rot, eggplant rod leaf spot, cucumber target spot, tomato leaf mold, eggplant leaf mold, broad bean red spot, citrus sphacelotheca (Phytobotrytis citricola), potato late blight (Phytophthora infens), Fusarium graminearum (Fusarium graminearum), Fusarium oxysporum (Fusarium), cucurbitella spinosum, etc., cucurbita scab, etc., and, At least one of Fusarium moniliforme (Fusarium moniliforme Sheldon), Fusarium solani (Mart.) Sacc.), Fusarium oxysporum (Fusarium oxysporum), Fusarium proliferatum (Fusarium proliferatum), Fusarium hutzeri (Colletotrichum higginsanum), Rhizoctonia solani (Rhizoctonia solani), and Magnaporthe oryzae (Pyricularia oryzae).
The grass includes but is not limited to at least one of broadleaf, georgette, cyperaceae, bolting genus, alismatis family, sedentaceae, scrophulariaceae, lythraceae, and broadleaf weeds; more preferably include, but are not limited to, Ageratum conyzoides L., Bidens pilosa L., Mikania micrantha Kunth, pseudobedstraw (Praxelis clevatia), R.M.King et H.Rob., Echinochloa cruris-galli, Digitaria digitata (Digitaria sanguinalis), Setaria viridis (Setaria viridis), Eleusine indica (Eleusines L.), Avena sativa L., Pseudosorghum halepense (Sorghum halepense), Iressay grass (Agropyron giralderiana), Alexanthera (Alexanthera paniculata), Brassica oleracea L., Sarcophylla (Sarcocephalus), Cysticta indica (Sarcophylla), Cysticta indica (Cysticta indica), Cysticta indica (Cysticta indica), Cysticta (Cysticta indica (Cysticta indica), Cysticta (Cysticta), Cysticta (Cysticta), Cysticta (Cysticta japonica), Cysticta (L), Cysticta (Cysticta), Cysticta (L.), Cysticta (Cysticta), Cysticta (, Narrow-leaf Alisma orientale (Alisma canadensis), Monochoria vaginalis (Monochoria vaginalis), Monochoria korsakowii), mirabilis procumbens (Lindernia pyindaria), gadfly eyes (Dopatrium Junceum), arthrodia (Rotala indica), Amaranthus multifida (amanini multiflora), Amaranthus retroflexus (Amaranthus retroflexus), Abutilon theopteris (Abutilon theopterus), morning glory (ipoea hederacea), Chenopodium quinoa (Chenopodium album), Sida tinctoria L., Portulaca oleracea L., Amaranthus viridans (Amaranthus flavus L.), garnetus sativus L., cassytha, setaria japonica (cassiopsis nigra L.), lycora sativa L., Polygonum sativum L., and Polygonum multiflorum (caraway), Polygonum fruticosum sativum L, Polygonum sativum L, and coides.
The anti-cancer drug is a drug capable of inhibiting growth, migration and/or reproduction of cancer cells and/or killing cancer cells; the cancer cells include but are not limited to at least one of human ovarian cancer cells A2780 and human breast cancer cells BT-20.
Particularly, the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects shows better poisoning effect on agricultural and sanitary pests such as plutella xylostella, spodoptera frugiperda, spodoptera exigua, prodenia litura, aedes aegypti, solenopsis invicta and Meloidogyne incognita (Kofold & White) Chitwood); the N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects of the present invention also exhibit better inhibitory effects on Photinus citricola (Phytolytica citricarpa), P6150 potato late blight (Phytophthora infestans), Fusarium graminearum (Fusarium graminearum Schwabe), Colletotrichum gloeosporioides, Fusarium moniliforme (Fusarium moniliforme Sheldon), Botrytis cinerea (Boytis cinerea), Fusarium solani (Mart.) Sacc.), Fusarium oxysporum (Fusarium oxysporum), Fusarium straticola (Fusarium proliferatum), Fusarium proliferatum), Fusarium chrysosporium (Collybum solanum (Mart.) and Rhizoctonia solani (Rhizoctonia solani) and the like; the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers has better killing and growth inhibition effects on barnyard grass, mikania micrantha, bidens pilosa, ageratum conyzoides, pseudo-rue bedstraw, eleusine indica and other agricultural weeds and harmful plants. The N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects also have good prevention effect on human ovarian cancer cells A2780 and human breast cancer cells BT-20.
The invention also provides a composition with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers, which comprises the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, killing weeds and resisting cancers or pharmaceutically acceptable salt thereof.
The N-difluoromethyl dinitrogen heterocyclic selenourea compound or the pharmaceutically acceptable salt thereof with the insecticidal, bacteriostatic, herbicidal and anticancer effects accounts for 0.01-99.99% of the weight of the composition with the insecticidal, bacteriostatic, herbicidal and anticancer effects.
The composition with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers further comprises a pharmaceutically acceptable carrier.
The carrier in the composition of the present invention is a substance satisfying the following conditions: it is formulated with active ingredients to facilitate application to the locus to be treated, which may be a plant, seed or soil; or to facilitate storage, transport or handling. The carrier may be a solid or a liquid, including materials which are normally gaseous but which have been compressed to form a liquid, and carriers which are normally used in formulating insecticidal compositions may be used.
The composition with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers can also comprise a surfactant.
The composition with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers is applied to the preparation of the drugs for killing insects, killing bacteria, weeding and resisting cancers.
The insecticidal, bactericidal, herbicidal and anticancer agents may be applied in the form of formulations. The preparation formulation comprises at least one of but not limited to powder, wettable powder, missible oil, concentrated emulsion and microemulsion, suspending emulsion, granules, oil solution, ultra-low volume spray, smoke type and sustained release agent.
The specific method of the application comprises the following steps: applying the pesticide to the pest or to a medium in which the pest is growing; the fungicide and herbicide are applied to a medium in which plants are grown.
For certain applications, for example, agricultural applications, one or more other types of insecticides, nematicides, acaricides, fungicides, herbicides, plant growth regulators, fertilizers, or the like can be added to the insecticide, fungicide, and herbicide compositions of the present invention, thereby providing additional advantages and benefits.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers shows good biological activity on pests in agriculture, forestry and other fields, plant pathogenic bacteria in agriculture, weeds and harmful plants in the agricultural field; the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers can be used as a pesticide and is used for preparing medicines for preventing and treating plant pathogenic bacteria and weeds in agriculture and forestry, and particularly the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers has better poisoning and killing effects on agricultural pests and sanitary pests such as plutella xylostella, spodoptera frugiperda, beet armyworm, prodenia litura, aedes aegypti, solenopsis invicta, meloidogyne incognita and the like; the N-difluoromethyl dinitroheterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects have better poisoning and growth-inhibiting effects on plant pathogenic bacteria such as phyllosticta citrullus, potato late blight bacteria, fusarium graminearum, botrytis cinerea, fusarium oxysporum, fusarium proliferatum, anthracnose of hujin, rhizoctonia solani and rice blast germs; the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers has better poisoning and growth inhibition effects on agricultural weeds and harmful plants such as barnyard grass, ageratum, bidens pilosa, mikania micrantha, pseudo-rue blumea herb, eleusine indica and the like. The N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects also has an inhibiting effect on human ovarian cancer cells A2780 and human breast cancer cells BT-20 generally.
(2) The inventor creatively discovers an N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects through a large number of experiments. The insecticidal activity of the compound is obviously superior to that of N-difluoromethyl benzimidazole selenourea compounds and N-difluoromethyl benzimidazole selenourea compounds discovered by the inventor in the earlier stage. In addition, the compounds have excellent antibacterial and herbicidal activities, and the functions are not possessed by N-difluoromethyl benzimidazole selenourea compounds and N-difluoromethyl benzimidazole selenourea compounds; in addition, the compound of the present invention also has a function of inhibiting cancer cells. The organic compound has a broad spectrum of biological activity in the pesticide and medicine fields, and the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers has important application value.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto. The raw materials related to the invention can be directly purchased from the market. For process parameters not specifically noted, reference may be made to conventional techniques.
Synthesis example 1: preparation of Compound D-1
Figure BDA0003574916350000111
Adding imidazo [1,5-A ] into a sealed tube]Pyridine (0.20mmol), selenium powder (0.40mmol), potassium carbonate (0.40mmol), and dissolved with 2mL acetonitrile (MeCN), followed by the addition of bromofluoroacetic acid ethyl ester (0.50 m)mol), sealing the reaction tube, and then placing the reaction tube in an oil bath kettle at 100 ℃ to stir and react for 24 hours. After TLC monitoring of the reaction, the reaction mixture was cooled to room temperature, extracted with ethyl acetate, and the combined organic phases were dried over anhydrous Na2SO4After drying, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluting with a mixed solvent of petroleum ether and ethyl acetate) to give a yellow solid product in 78.0% yield.
Preparation of Compound D-6
Figure BDA0003574916350000112
Adding imidazo [1,5-A ] into a sealed tube]Pyridine-1-carboxylic acid ethyl ester (0.20mmol), selenium powder (0.40mmol), potassium carbonate (0.40mmol), and dissolved with 2mL acetonitrile (MeCN), followed by the addition of bromofluoroacetic acid ethyl ester (0.50mmol), sealing the reaction tube and placing in a 100 ℃ oil bath for stirring reaction for 24 h. After TLC monitoring of the reaction, the reaction mixture was cooled to room temperature, extracted with ethyl acetate, and the combined organic phases were dried over anhydrous Na2SO4After drying, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluting with a mixed solvent of petroleum ether and ethyl acetate) to give a yellow solid product with a yield of 85.06%.
Preparation of Compound D-11
Figure BDA0003574916350000113
Adding [1,2,4 ] into a sealed tube]Triazolo [4,3-A]Pyridine (0.20mmol), selenium powder (0.40mmol), potassium carbonate (0.40mmol), and dissolved with 2mL acetonitrile (MeCN), followed by the addition of bromofluoroacetic acid ethyl ester (0.50mmol), the reaction tube was sealed and placed in a 100 ℃ oil bath and stirred for reaction for 24 h. After TLC monitoring of the reaction, the reaction mixture was cooled to room temperature, extracted with ethyl acetate, and the combined organic phases were dried over anhydrous Na2SO4After drying, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluting with a mixed solvent of petroleum ether and ethyl acetate) to give a yellow solid product with a yield of 86.0%.
Preparation of Compound D-12
Figure BDA0003574916350000121
Adding 8-fluoro- [1,2,4 ] to a sealed tube]Triazolo [4,3-A]Pyridine (0.20mmol), selenium powder (0.40mmol), potassium carbonate (0.40mmol), and dissolved with 2mL acetonitrile (MeCN), followed by the addition of bromofluoroacetic acid ethyl ester (0.50mmol), the reaction tube was sealed and placed in a 100 ℃ oil bath and stirred for reaction for 24 h. After TLC monitoring of the reaction, the reaction mixture was cooled to room temperature, extracted with ethyl acetate, and the combined organic phases were dried over anhydrous Na2SO4After drying, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluting with a mixed solvent of petroleum ether and ethyl acetate) to give a yellow solid product with a yield of 40.0%.
Preparation of Compound D-24
Figure BDA0003574916350000122
Adding 1,2, 4-triazolo [3,4-a ] into a sealed tube]Isoquinoline (0.20mmol), selenium powder (0.40mmol), potassium tert-butoxide (0.40mmol) and dissolved in 2mL acetonitrile (MeCN), followed by the addition of bromofluoroacetic acid ethyl ester (0.50mmol), the reaction tube was sealed and placed in a 100 ℃ oil bath and stirred for reaction for 24 h. After TLC monitoring of the reaction, the reaction mixture was cooled to room temperature, extracted with ethyl acetate, and the combined organic phases were dried over anhydrous Na2SO4After drying, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluting with a mixed solvent of petroleum ether and ethyl acetate) to give a yellow solid product with a yield of 32.67%.
Compounds D1-D27 were prepared with reference to the procedure for compound D-1.
Nuclear magnetic data for some compounds (other compounds except where noted:1H NMR,500MHz；13c NMR,126MHz, internal standard TMS, solvent: CDCl3) The following were used:
compound D-1: a pale yellow solid. DeltaH＝8.42(dd,J＝7.44Hz,0.90,1H),8.08(t,J＝59.41Hz,1H),7.44(s,1H),7.24(d,J＝9.41Hz,1H),6.89(dd,J＝9.34Hz,6.42,1H),6.74–6.57(m,1H)；δC＝148.72,130.26,126.05,124.52,117.74,114.14,110.42(t,JC-F＝253.90Hz,1C)103.76。
Compound D-2: yellow solid. DeltaH＝8.62(s,1H),8.03(t,J＝59.31Hz,1H),7.46(s,1H),7.15(d,J＝9.76Hz,1H),6.92(dd,J＝9.77Hz,1.40,1H)；δC＝149.13,128.69,128.47,125.78,118.45,110.31(t,JC-F＝254.67Hz,1C),110.11,104.91.
Compound D-3: a white solid. DeltaH＝7.63(t,J＝59.81Hz,1H),6.76(s,1H),3.75(t,J＝6.33Hz,2H),2.56(t,J＝6.34Hz,2H),1.82(dt,J＝12.19Hz,6.19,2H),1.71–1.60(m,2H)；δC＝155.48(t,JC-F＝3.46Hz,1C),129.93,109.38(t,JC-F＝250.49Hz,1C),108.71,45.37,21.86,20.52,19.00.
Compound D-4: yellow solid. DeltaH＝8.82(s,1H),8.07(dd,J＝86.96Hz,31.6,2H),7.74(s,1H),7.59(d,J＝5.22Hz,1H)；δC＝150.83,146.71,128.98,125.62,117.29,110.07(t,JC-F＝258.54Hz,1C),108.00.
Compound D-5: yellow solid. DeltaH＝10.09(s,1H),8.71(d,J＝7.2Hz,1H),8.41(t,J＝57.96Hz,1H),8.24(d,J＝9.23Hz,1H),7.52–7.43(m,1H),7.04(t,J＝6.90Hz,1H)；δC＝175.41,155.74,135.03,132.74,127.66,119.32,117.43,114.28(t,JC-F＝255.52Hz,1C),110.23.
Compound D-6: a red solid. DeltaH＝8.70(d,J＝7.28Hz,4H),8.70(d,J＝7.28Hz,4H),8.59(s,1H),8.48(s,2H),8.48(t,J＝57.87Hz,4H),8.36(s,1H),8.00(d,J＝9.42Hz,4H),8.00(d,J＝9.42Hz,4H),7.30–7.24(m,5H),7.31–7.23(m,5H),6.88(t,J＝6.91Hz,4H),6.88(t,J＝6.91Hz,4H),4.44(q,J＝7.13Hz,8H),1.43(t,J＝7.14Hz,13H)；δC＝157.18,155.96,135.42,130.04,127.44,119.19,115.31,111.91(t,JC-F＝259.43Hz,1C),109.71,61.55,14.16.
Compound D-7: a red solid. DeltaH＝8.48(d,J＝7.30Hz,1H),7.95(dd,J＝86.16Hz,32.0,2H),7.62(d,J＝6.774Hz,1H),6.64(t,J＝7.03Hz,1H),4.35(q,J＝7.06Hz,2H),1.35(t,J＝7.11Hz,3H)；δC＝162.32,149.81,130.16,129.69,126.90,120.80,112.70,110.09(t,JC-F＝254.26Hz,1C),106.33,61.65,13.87.
Compound D-8: a red solid. DeltaH＝8.54(d,J＝7.27Hz,1H),8.17–7.86(m,2H),7.66(d,J＝6.67Hz,1H),6.68(t,J＝7.04Hz,1H),3.92(s,3H)；δC＝162.98,150.02,130.52,130.04,126.99,120.73,112.81,110.23(t,JC-F＝254.44Hz,1C),106.60,52.61.
Compound D-9: a white solid. Delta. for the preparation of a coatingH＝8.05(t,J＝57.33Hz,1H),4.45(s,2H),3.99(s,2H),3.80(s,2H),1.48(s,9H)；δC＝159.60,153.62,126.00,111.32(t,JC-F＝255.01Hz,1C),92.34,81.80,45.39,40.15(d,JC-F＝261.59Hz,1C),29.61,28.20.
Compound D-10: a white solid. DeltaH＝7.81(t,J＝59.51Hz,1H),6.99(s,1H),4.58(s,2H),4.03(t,J＝5.51Hz,2H),3.82(t,J＝5.54Hz,2H),1.48(s,9H)；δC＝157.51,153.77,126.59,109.90(t,JC-F＝251.77Hz,1C),108.70,81.63,63.78,44.77,29.66,28.25.
Compound D-11: yellow solid. DeltaH＝8.49(d,J＝7.20Hz,1H),8.10(t,J＝57.56Hz,1H),7.54(d,J＝9.45Hz,1H),7.47(ddd,J＝9.43Hz,6.50,0.99,1H),7.01–6.91(m,1H)；δC＝157.91,147.96,133.16,126.92,115.86,114.74,108.53(t,JC-F＝255.91Hz,1C).
Compound D-12: yellow solid. DeltaH＝8.33(d,J＝7.14Hz,1H),8.06(t,J＝57.36Hz,1H),7.17(dd,J＝9.02Hz,7.91,1H),6.91(td,J＝7.33Hz,4.14,1H)；δC＝158.98,150.25,148.16,123.37(d,JC-F＝5.77Hz,1C),114.53(d,JC-F＝15.08Hz,1C),113.69(d,JC-F＝5.26Hz,1C),108.45(t,JC-F＝257.10Hz,1C).
Compound D-13: yellow solid. DeltaH＝8.43(dd,J＝7.14Hz,0.82,1H),8.07(t,J＝57.38Hz,1H),7.52(dd,J＝7.19Hz,0.78,1H),6.91(t,J＝7.17Hz,1H)；δC＝159.48,146.37,131.60,125.62,122.07,114.36,108.47(t,JC-F＝257.07Hz,1C).
Compound D-14: a white solid. DeltaH＝8.48(d,J＝7.11Hz,1H),8.07(t,J＝57.38Hz,1H),7.72(d,J＝7.07Hz,1H),6.85(t,J＝7.13Hz,1H)；δC＝159.51,146.89,135.30,126.19,114.80,109.25,108.49(t,JC-F＝257.08Hz,1C).
Compound D-15: yellow solid. DeltaH＝8.65(d,J＝7.16Hz,1H),8.06(t,J＝57.30Hz,1H),7.83(d,J＝6.90Hz,1H),7.03(t,J＝7.04Hz,1H)；δC＝159.09,143.80,132.43,130.38,122.09,119.92,113.01,108.47(t,JC-F＝257.47Hz,1C).
Compound D-16: yellow solid. DeltaH＝8.42(s,1H),8.04(t,J＝57.47Hz,1H),7.58(dd,J＝10.09Hz,4.50,1H),7.43(ddd,J＝9.83Hz,7.39,2.14,1H)；δC＝158.14,153.91(d,JC-F＝246.63Hz,1C),146.01,127.47(d,JC-F＝28.92Hz,1C),117.28(d,JC-F＝8.20Hz,1C),113.05(d,JC-F＝43.74Hz,1C),108.47(t,JC-F＝256.55Hz,1C).
Compound D-17: yellow solid. DeltaH＝8.53(s,1H),8.03(t,J＝57.46Hz,1H),7.51(d,J＝9.81Hz,1H),7.41(dd,J＝9.85Hz,1.70,1H)；δC＝157.73,146.38,135.37,124.39,123.84,116.50,108.43(t,JC-F＝259.58Hz,1C).
Compound D-18: yellow solid. DeltaH＝8.82(s,1H),8.03(t,J＝57.10Hz,1H),7.66(d,J＝9.78Hz,1H),7.54(d,J＝9.76Hz,1H)；δC＝160.10,147.30,128.91(d,JC-F＝2.28Hz,1C),126.59(q,JC-F＝6.03Hz,1C),122.18(q,JC-F＝271.87Hz,1C),119.45(q,JC-F＝35.42Hz,1C)，117.37,108.39(t,JC-F＝256.91Hz,1C).
Compound D-19; yellow solid. DeltaH＝8.26(d,J＝1.18Hz,1H),8.08(t,J＝57.60Hz,1H),7.45(d,J＝9.54Hz,1H),7.32(dd,J＝9.55Hz,1.41,1H),2.36(d,J＝1.10Hz,3H)；δC＝156.74,147.26,136.85,125.10,123.54,115.00,108.48(t,JC-F＝255.72Hz,1C),18.16.
Compound D-20: yellow solid. DeltaH＝8.27(d,J＝7.13Hz,1H),8.07(t,J＝57.60Hz,1H),7.18(d,J＝6.69Hz,1H),6.84(t,J＝6.93Hz,1H),2.49(s,3H)；δC＝157.83,148.61,130.67,126.35,124.18,114.99,108.41(t,JC-F＝255.47Hz,1C),15.88.
Compound D-21: a white solid. Delta. for the preparation of a coatingH＝7.75(t,J＝57.73Hz,1H),3.84(t,J＝6.15Hz,2H),2.84(t,J＝6.43Hz,2H),2.06–1.80(m,4H)；δC＝163.64,151.81,107.59(t,JC-F＝252.98Hz,1C),44.80,21.84,21.41,18.94.
Compound D-22: yellow solid. Delta. for the preparation of a coatingH＝9.18(d,J＝1.54Hz,1H),8.28(dd,J＝4.90Hz,1.65,1H),8.21–7.96(m,2H)；δC＝160.22,141.50,136.28,128.28(d,JC-F＝3.11Hz,1C),125.82,109.47(t,JC-F＝254.78Hz,1C).
Compound D-23: a pale yellow solid. DeltaH＝8.34(d,J＝7.29Hz,1H),8.05(t,J＝57.61Hz,1H),7.25(s,1H),6.75(d,J＝7.28Hz,1H),2.43(s,3H)；δC＝157.30,148.20,144.99,125.66,117.97,112.91,108.50(t,JC-F＝255.38Hz,1C),21.93.
Compound D-24: white solid. DeltaH＝10.94(d,J＝8.49Hz,1H),8.26(t,J＝57.84Hz,1H),7.69(dd,J＝12.77Hz,4.54,2H),7.66–7.57(m,2H),7.32(d,J＝9.65Hz,1H)；δC＝157.90,147.56,135.06,134.15,129.73,128.99,127.78,124.03,117.72,113.02,108.30(t,JC-F＝255.90Hz,1C).
Compound D-25: a white solid. DeltaH＝7.77(t,J＝57.52Hz,1H),4.72(s,2H),3.88(dd,J＝34.86Hz,5.11,4H),1.44(s,9H)；δC＝164.22,153.22,148.37,107.64(t,JC-F＝254.00Hz,1C),82.01,60.14,44.04,40.54,28.00.
Compound D-26, a yellow solid. DeltaH＝8.77(d,J＝1.21Hz,1H),8.02(t,J＝57.21Hz,1H),7.60(s,1H)；δC＝161.54,145.86,127.27(d,JC-F＝2.36Hz,1C),125.09(dd,JC-F＝6.16Hz,12.20Hz 1C),123.99,121.26(q,JC-F＝249.12Hz,1C),119.38(q,JC-F＝35.99Hz,1C),108.38(t,JC-F＝258.02Hz,1C).
Compound D-27, a yellow solid. DeltaH＝8.79(s,1H),8.01(t,J＝57.22Hz,1H),7.84(s,1H)；δC＝158.57,136.37(q,JC-F＝4.90Hz,1C),129.96,127.27(q,JC-F＝273.61Hz,1C),119.58(q,JC-F＝37.25Hz,1C),108.41(t,JC-F＝258.17Hz,1C),107.98,99.97.
The structural formula of the compound is as follows:
Figure BDA0003574916350000151
examples of biological Activity assays
Example 1: evaluation of in vitro Activity of partial Compounds on partial human cancer cells
Test cancer cell number: human ovarian cancer cell A2780 (cell catalog number: SNL-132, available from Wuhanshanshangen Biotech Co., Ltd.), and human breast cancer cell BT-20 (cell catalog number YS2191C, available from Yaji Biotech Co., Ltd., Shanghai).
The operation process is as follows: culturing the purchased cells, and taking out the cells for standby when the number of the cells is enough and the cell state is good. The concentration of the cell suspension was adjusted to 2.0X 104～5×104one/mL. The cell suspension was then seeded into 96-well plates (100. mu.L/well) and placed under saturated humidity 5% CO2And cultured in an incubator at 37 ℃ for 24 hours, the test compound is diluted with the medium to a corresponding concentration (1. mu.M), added to a 96-well plate inoculated with human tumor cells, cultured, and placed in the incubator to continue the culture. After 72 hours, MTT (20. mu.L/well) was added. Incubate for 4 hours in the incubator, aspirate the liquid from the discard well, add DMSO (150. mu.L/well), and shake on a shaker for 10 minutes. The absorbance at a wavelength of 570nm was then measured with a microplate reader, the absorbance at 630nm was used as a reference, and the corresponding solvent was used as a control. And (5) calculating the inhibition rate of the cells.
The experimental results are as follows: the inhibitory activity of each compound on cancer cells A2780 and BT-20 is shown in Table 1 below:
table 1:
Figure BDA0003574916350000161
Figure BDA0003574916350000171
the compound of the invention shows good activity to various pests in the agricultural field. The results of the insecticidal activity measurement are shown in the following examples.
Example 2: evaluation of insecticidal Activity of partial Compounds on Plutella xylostella
The tested insects are lepidoptera plutella xylostella and are bred indoors with sensitive strains. The 3 rd larva of diamondback moth is taken as a test object, and the test method is a leaf soaking method.
The operation process is as follows: each sample was accurately weighed, DMSO was added to prepare a 10g/L stock solution, and the stock solution was diluted to 50ppm with a 0.5% aqueous solution of Tween 80. Preparing clean leaf dish with 1.0cm diameter puncher, soaking in the medicinal liquid for 10s, taking out, air drying, and transferring into clean container. Inoculating 3-year-old larvae of diamondback moth with consistent growth into a vessel, inoculating 10 test insects for each treatment, and feeding at constant temperature of 28 ℃. Assuming 3 replicates, the control group was treated with an aqueous solution containing an equivalent amount of 0.5% tween 80 DMSO. After 96h the test results were observed and the mortality (%) was calculated according to the formula. The death rate (%) < dead insect number/test insect number x 100%. The test results are shown in Table 2.
Example 3: evaluation of insecticidal activity of partial compounds on Spodoptera frugiperda
The tested insects were Lepidoptera Spodoptera frugiperda, and the sensitive strains were raised indoors. The late stage 2 instar larvae of Spodoptera frugiperda are used as test objects, and the test method is a leaf soaking method.
The operation process is as follows: each sample was accurately weighed, DMSO was added to prepare a 10g/L stock solution, and the stock solution was diluted to 50ppm with a 0.5% aqueous solution of Tween 80. Making clean corn leaves into leaf disks by using a puncher with the diameter of 1.0cm, soaking the leaf disks into the liquid medicine, taking out the leaves after 10 seconds, naturally drying the leaves, and transferring the leaves into a clean vessel. Inoculating 2-instar late stage Spodoptera frugiperda larvae with consistent growth into a vessel, inoculating 10 test insects for each treatment, and feeding at constant temperature of 28 ℃. In 3 replicates, the control group was treated with an equal amount of 0.5% aqueous tween 80 DMSO. After 96h the test results were observed and the mortality (%) was calculated according to the formula. The death rate (%) < dead insect number/test insect number x 100%. The test results are shown in Table 2.
Example 4: evaluation of insecticidal Activity of partial Compounds on beet armyworm
The tested insects are lepidoptera spodoptera exigua, and sensitive strains are raised indoors. The 1 st-instar metaphase larva of beet armyworm is taken as a test object, and the test method is a leaf soaking method.
The operation process is as follows: each sample was accurately weighed, DMSO was added to prepare a 10g/L stock solution, and the stock solution was diluted to 50ppm with a 0.5% aqueous solution of Tween 80. Preparing clean leaf dish with 1.0cm diameter puncher, soaking in the medicinal liquid for 10s, taking out, air drying, and transferring into clean container. Inoculating 1-instar metaphase larva of beet armyworm with consistent growth into a vessel, inoculating 10 test insects for each treatment, and feeding in a constant temperature incubator at 28 ℃. In 3 replicates, the control group was treated with an equal amount of 0.5% aqueous tween 80 DMSO. After 96h the test results were observed and the mortality (%) was calculated according to the formula. The death rate (%) < dead insect number/test insect number x 100%. The test results are shown in Table 2.
Example 5: evaluation of insecticidal Activity of partial Compounds on Spodoptera litura
The tested insects are Lepidoptera prodenia litura, and sensitive strains are raised indoors. The final stage larva of the 1 st age of prodenia litura is taken as a test object, and the test method is a leaf soaking method.
The operation process is as follows: each sample was accurately weighed, DMSO was added to prepare a 10g/L stock solution, and the stock solution was diluted to 50ppm with a 0.5% aqueous solution of Tween 80. Preparing clean leaf dish with 1.0cm diameter puncher, soaking in the medicinal liquid for 10s, taking out, air drying, and transferring into clean container. Inoculating 1-th-instar late-stage spodoptera litura larvae with consistent growth into a vessel, inoculating 10 test insects for each treatment, and feeding at constant temperature of 28 ℃. In 3 replicates, the control group was treated with an equal amount of 0.5% aqueous tween 80 DMSO. After 96h the test results were observed and the mortality (%) was calculated according to the formula. The death rate (%) < dead insect number/test insect number x 100%. The test results are shown in Table 2.
Example 6: evaluation of insecticidal Activity of partial Compounds against Aedes aegypti
The tested insects were aedes aegypti, and the sensitive strains were raised indoors. The 3 rd larva of aedes aegypti was used as the test object.
The operation process is as follows: each sample was accurately weighed, DMSO was added to prepare a 10g/L mother liquor, and the mother liquor was diluted to 50ppm with distilled water. A plastic cup with the diameter of about 5cm and the height of 7cm is taken as a container, a preservative film with small holes is covered to prevent water from evaporating and losing and keep ventilation, and 10 aedes aegypti larvae of 3 th instar are inoculated into each small cup. The control group was treated with an equal volume of DMSO in distilled water (typically less than 1% treatment organic solvent), and each treatment was repeated 3 times. Treating the environment in a light incubator under the following conditions: 25 +/-2 ℃, 16h/8h (L/D) and 80 percent of relative humidity. After 48h the test results were observed and the mortality (%) was calculated according to the formula. The death rate (%) < dead insect number/test insect number x 100%. The test results are shown in Table 2.
Example 7: evaluation of insecticidal Activity of partial Compound against Solenopsis invicta
Dissolving the compound with acetone, diluting with acetone, water and Tween 80 to 50mg/L (i.e. 50ppm), wherein acetone content is 0.3% (v/v), Tween 80 content is 0.2% (v/v), and the control group comprises: acetone, water and Tween 80, wherein the acetone content is 0.3% (v/v), and the Tween 80 content is 0.2% (v/v). The diluted liquid medicine is added into a centrifugal tube with the volume of 2.0mL, and the opening of the tube is blocked by absorbent cotton, so that the liquid does not flow out when the absorbent cotton is wetted. Coating a layer of talcum powder at a position 2.5cm away from the cup opening on the inner side of a dry plastic cup, inserting 20 pieces of middle-sized fire ant workers with the same size into each cup, after hunger treatment for 5 hours, respectively placing a water test tube and a proper amount of fresh ham sausages into the corresponding plastic cups, and repeating the treatment for 3 times. After the treatment, the plastic cups are placed in an insect-raising room and raised at a constant temperature of 25 ℃. The results were recorded and corrected mortality was calculated after 48h of treatment. Corrected mortality-control mortality)/(1-control mortality) x 100%. The test results are shown in Table 2.
Example 8: evaluation of insecticidal Activity of partial Compounds on Meloidogyne incognita
Meloidogyne incognita is kept in the university of agriculture, south China research laboratory for plant pathogenic nematodes. The test insect source parasitized the tomato roots. The operation process is as follows: removing mud from the root of the damaged tomato, sterilizing with 0.5% sodium hypochlorite for 2min, selecting fresh oocysts from root knots generated by the damaged tomato under a stereomicroscope, placing the oocysts in a culture dish filled with sterile water and having a diameter of 90mm, culturing in an incubator at (25 +/-1) DEG C, and collecting nematodes for later use after 3d when eggs hatch to generate a large amount of 2-year larvae. The insecticidal activity is tested by adopting an immersion method: dissolving a compound to be detected by using acetone, preparing a medicament with the concentration of 50ppm, sucking 0.5mL of different liquid medicines, adding the liquid medicines into a 24-hole cell culture plate, picking about 30 heads of Meloidogyne incognita from each hole, and repeating the steps for 3 times. The death rate of the test insects is recorded at 48h, and the death rate (%) is calculated and the same amount of acetone aqueous solution is used as a control. The nematode worms are gently stirred by a needle under a stereomicroscope, and are considered to die when the worms are stiff and immobile, the body wall is not smooth, and the body is white and shiny; all insects moving in S, L or wave form are considered as live insects. The test results are shown in Table 2.
Table 2: insecticidal activity test of some of the compounds of the present invention against 4 lepidopteran pests and other pests
Figure BDA0003574916350000191
Note: the test concentration of the compound was 50 ppm.
LC with best insecticidal activity on three-instar diamondback moth in earlier developed N-difluoromethyl benzimidazole and N-difluoromethyl imidazole selenourea compounds50Is 33.2mg/L, LC of the inventive compound50LC of a majority of less than 25mg/L, a portion of the compounds50Less than 20 mg/L; LC of compound of the invention to two-instar plutella xylostella50Less than 4 mg/L. In general, the compound of the invention is obviously superior to the benzimidazole selenourea compound and the imidazole selenourea compound developed in the prior art in the aspect of insecticidal activity.
The compound of the invention has good activity to a plurality of plant pathogenic bacteria in the agricultural field, and the result of the antibacterial activity is shown in the following examples.
Example 9: evaluation of in vitro bacteriostatic activity of part of compounds on Phycomyces citricola (Phyllosticta citricarpa)
The operation process is as follows: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were cut on a growing fungal (Phyllosticta citricola) culture using a punch to grow and the hyphae were transferred to petri dishes containing the test compounds. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 5 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent (%) inhibition (average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Example 10: evaluation of partial compound on P6150 potato late blight bacterium in vitro antibacterial activity
The operation process is as follows: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were cut on a growing fungal (P6150 potato late blight) culture using a punch and grown and the hyphae were transferred to petri dishes containing the test compounds. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 6 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent inhibition (%) ═ average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Example 11: evaluation of partial compound on in-vitro bacteriostatic activity of fusarium graminearum
The operation process is as follows: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were cut on the growing fungal (fusarium graminearum) culture using a punch and grown and the hyphae were transferred to a petri dish containing the test compound. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 5 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent inhibition (%) ═ average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Example 12: evaluation of partial compounds on in-vitro bacteriostatic activity of fusarium oxysporum
The operation process comprises the following steps: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were cut on the growing fungal (fusarium oxysporum) culture using a punch and grown and the hyphae were transferred to petri dishes containing the test compounds. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 5 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent inhibition (%) ═ average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Example 13: evaluation of in vitro bacteriostatic activity of part of compounds on botrytis cinerea
The operation process is as follows: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were grown on the growing fungal (Botrytis cinerea) culture using a punch and transferred to a petri dish containing the test compound. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 7 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent inhibition (%) ═ average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Example 14: evaluation of partial compounds on in-vitro bacteriostatic activity of Higgins anthracnose bacteria
The operation process is as follows: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were cut on the growing fungal (anthrax Higgins) culture using a punch and grown and the hyphae were transferred to petri dishes containing the test compounds. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 7.5 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent inhibition (%) ═ average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Example 15: evaluation of partial compound on in-vitro bacteriostatic activity of rhizoctonia solani
The operation process is as follows: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were cut on the growing fungal (rhizoctonia solani) culture using a punch to grow and the hyphae were transferred to a petri dish containing the test compound. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 1.5 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent inhibition (%) ═ average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Example 16: evaluation of in vitro antibacterial activity of partial compounds on rice blast fungus
The operation process is as follows: each test compound was dissolved in an appropriate amount of acetone and diluted with water (containing 0.1% TW-80) to a concentration of 250 ppm. To each dish was added 1 ml of test solution and 9 ml of medium to give a concentration of 25ppm of test compound, while to the other dish was added 1 ml of distilled water containing 0.1% TW-80 and 9 ml of medium as a blank. Hyphae with a diameter of 9mm were cut on the growing fungal (Pyricularia oryzae) culture using a punch and grown, and the hyphae were transferred to a petri dish containing the test compound. Each assay was performed in triplicate. The petri dishes were stored in a controlled environment cabinet (28 ± 1 ℃) for 8 days, after which the diameter of hyphal growth was measured and the percentage inhibition was calculated using the following equation: percent inhibition (%) ═ average diameter of mycelium in blank-average diameter of mycelium in drug tablet)/(average diameter of mycelium in blank-9 mm) × 100%. The test results are shown in Table 3.
Table 3: bacteriostatic activity test of partial compounds of the invention on 8 plant pathogenic bacteria
Figure BDA0003574916350000221
Note: the test concentration of the compound was 25ppm, the test strain was introduced from the oceanic college of southern China agricultural university and deposited at the Material and energy college of southern China agricultural university, and the strain number is shown in Table 4.
Table 4: 8 Strain number of plant pathogenic bacteria
Figure BDA0003574916350000231
Note: in Table 4, Cijin anthrax and Botrytis cinerea were purchased from Beijing Beinanna Chuanglian Biotech research institute, Phoma citrifolia was purchased from Shanghai Ruiz Biotech Co., Ltd, and Magnaporthe grisea was purchased from Shanghai West Biotech Co., Ltd; the rest strains are purchased from a Chinese microbial strain inquiry network.
Part of the compounds EC against Rhizoctonia solani50The results are given in table 5 below:
table 5: EC of Rhizoctonia solani50
Compound (I) R2 EC50 Fang Cheng Confidence interval
D-23 10.388-78.544 17.418 Y＝2.84X-3.53 0.961
D-15 7.460-17.300 11.097 Y＝4.57X-4.61 0.973
D-20 7.545-52.256 13.494 Y＝1.45X-1.63 0.906
D-24 1.602-3.632 2.317 Y＝2.09X-0.79 0.952
D-18 6.463-14.410 9.313 Y＝2.73X-2.63 0.973
D-27 2.336-3.497 2.914 Y＝1.63X-0.76 0.960
D-26 5.014-12.327 7.636 Y＝2.8X-2.36 0.948
D-19 5.212-13.089 7.968 Y＝2.64X-2.227 0.941
D-5 9.966-20.798 13.418 Y＝1.32X-1.52 0.951
D-9 8.002-15.527 10.513 Y＝1.41X-1.41 0.960
D-13 8.708-41.917 14.486 Y＝1.95X-2.25 0.931
D-17 6.455-8.959 7.572 Y＝1.74X-1.52 0.975
D-12 7.883-25.712 12.274 Y＝1.67X-1.81 0.945
D-16 16.264-31.973 21.478 Y＝1.27X-1.7 0.954
The results of the antibacterial activity tests in tables 3 and 5 show that the N-difluoromethyl dinitroheterocyclic selenourea compound has excellent antibacterial activity. In particular, the half-inhibitory concentration of the D-27 compound to rhizoctonia solani reaches 2.317(Y is 1.63X-0.76, R20.960, confidence interval is: 2.336-3.497). The N-difluoromethyl benzimidazole selenourea and the N-difluoromethyl imidazole selenourea compounds synthesized by the inventor in the earlier stage have almost no bacteriostatic activity on the plant pathogenic bacteria at the concentration of 25 mg/L.
The compounds of the present invention exhibit excellent activity against various weeds and harmful plants in the agricultural field, and the results of the measurement of herbicidal activity are shown in the following examples.
Example 17: evaluation of herbicidal Activity of partial Compounds on ageratum conyzoides
Pre-treatment for pregermination: soaking weed seeds (ageratum conyzoides seeds) in 15% sodium hypochlorite for 15min, washing with tap water for several times, and washing with distilled water for 2-3 times. Soaking the seeds of ageratum conyzoides in 200 mg.L-1Taking out the seeds after 28h from the gibberellin aqueous solution, and washing the seeds for 2-3 times for later use by using distilled water. Qualitative filter paper with a diameter of 9.0cm was placed in a petri dish, and 3mL of distilled water was respectively sucked to uniformly wet the filter paper. 40-50 ageratum seeds (the number of the seeds is different according to the size of the seeds) are uniformly placed in each culture dish, distilled water is dripped again until the seeds do not float, and a preservative film with small holes is covered to ensure ventilation and prevent water evaporation. Placing the seeds in a light incubator at 25 +/-2 ℃ for 16h/8h (L/D) and relative humidity of 80 percent for 2-3D, and picking the seeds which just expose white for later use.
Experimental treatment: each test compound was dissolved in an appropriate amount of acetone, diluted with water (containing 0.1% TW-80) to a concentration of 10g/L, and further diluted with acetone + water + Tween 80 to 25 mg/L. A plastic cup with the diameter of about 5cm and the height of 7cm is used as a container, 3-4 layers of glass beads with the diameter of about 0.4cm are added into the cup, the glass beads are distributed in the plastic cup, a preservative film with small holes is covered on the plastic cup, the moisture evaporation and dissipation are prevented, the air permeability is kept, and 10-15 exposed and white ageratum seeds are placed in each small cup. The control group was treated with an equal volume of distilled water containing acetone (typically less than 1% of organic solvent), and each treatment was repeated 3 times. Treating the environment in a light incubator under the following conditions: 25 +/-2 ℃, 16h/8h (L/D) and 80 percent of relative humidity. And 7d, observing the growth condition of the roots and the overall condition of the plants, photographing, measuring the fresh weight, measuring the root length by using Image-Pro Plus 6.0 software, and calculating the root length and the fresh weight inhibition rate. Root length inhibition (%) - (control root length-treated root length)/control root length × 100%; fresh weight inhibition (%) - (control fresh weight-treated fresh weight)/control fresh weight × 100%. The test results are shown in tables 6 and 7.
Example 18: evaluation of herbicidal Activity of partial Compounds on Bidens pilosa
Pre-treatment for pregermination: soaking weed seeds (bidens pilosa L.) in 15% sodium hypochlorite for 15min, washing with tap water for several times, and washing with distilled water for 2-3 times. Soaking herba Bidentis Bipinnatae seed in 200 mg.L-1Taking out the seeds after 28h from the gibberellin aqueous solution, and washing the seeds for 2-3 times for later use by using distilled water. Qualitative filter paper with a diameter of 9.0cm was placed in a petri dish, and 3mL of distilled water was respectively sucked to uniformly wet the filter paper. 40-50 bidens pilosa seeds (different in quantity according to the size of the seeds) are evenly placed in each culture dish respectively, distilled water is dripped again until the seeds do not float, and a preservative film with small holes is covered to ensure ventilation and prevent water evaporation. The culture medium is placed in a light incubator with the temperature of 25 +/-2 ℃, the temperature of 16h/8h (L/D) and the relative humidity of 80 percent. And after 2-3 days, selecting the seeds which just expose white for later use.
Experimental treatment: each test compound was dissolved in an appropriate amount of acetone, diluted with water (containing 0.1% TW-80) to a concentration of 10g/L, and then diluted with acetone + water + Tween 80 to 25 mg/L. A plastic cup with the diameter of about 5cm and the height of 7cm is taken as a container, 3-4 layers of glass beads with the diameter of about 0.4cm are added into the cup, the glass beads are distributed in the plastic cup, a preservative film with small holes is covered, evaporation and dissipation of water are prevented, ventilation is kept, and 10-15 pieces of exposed bidens pilosa seeds are placed in each small cup. The control group was treated with an equal volume of distilled water containing acetone (typically less than 1% of organic solvent), and each treatment was repeated 3 times. Treating the environment in a light incubator under the following conditions: 25 +/-2 ℃, 16h/8h (L/D) and 80 percent of relative humidity. And 7d, observing the growth condition of the roots and the overall condition of the plants, photographing, measuring the fresh weight, measuring the root length by using Image-Pro Plus 6.0 software, and calculating the root length and the fresh weight inhibition rate. Root length inhibition (%) - (control root length-treated root length)/control root length × 100%; fresh weight inhibition (%) - (control fresh weight-treated fresh weight)/control fresh weight × 100%. The test results are shown in tables 6 and 7.
Example 19: evaluation of herbicidal Activity of partial Compound on Mikania micrantha
Pre-treatment for germination acceleration: soaking weed seeds (mikania micrantha seeds) in 15% sodium hypochlorite for 15min, washing with tap water for several times, and washing with distilled water for 2-3 times. Then soaking mikania micrantha seeds in 200 mg.L-1Taking out the seeds after 28h from the gibberellin aqueous solution, and washing the seeds for 2-3 times for later use by using distilled water. Qualitative filter paper with a diameter of 9.0cm was placed in a petri dish, and 3mL of distilled water was respectively sucked to uniformly wet the filter paper. 40 ~ 50 grains (place the quantity difference according to the size of seed) of mikania micrantha seed are evenly placed respectively to every culture dish, and the dropwise add distilled water again till the seed does not float, covers to prick the plastic wrap of aperture in order to guarantee ventilative and prevent the moisture evaporation. The culture medium is placed in a light incubator with the temperature of 25 +/-2 ℃, the temperature of 16h/8h (L/D) and the relative humidity of 80 percent. And after 2-3 days, selecting the seeds which just expose white for later use.
Experimental treatment: each test compound was dissolved in an appropriate amount of acetone, diluted with water (containing 0.1% TW-80) to a concentration of 10g/L, and further diluted with acetone + water + Tween 80 to 25 mg/L. A plastic cup with the diameter of about 5cm and the height of 7cm is used as a container, 3-4 layers of glass beads with the diameter of about 0.4cm are added into the cup, the glass beads are distributed in the plastic cup, a preservative film with small holes is covered on the plastic cup, the moisture is prevented from evaporating and losing, the air permeability is kept, and 10-15 whitish mikania micrantha seeds are placed into each small cup. The control group was treated with an equal volume of acetone in distilled water (typically less than 1% treatment organic solvent), and each treatment was repeated 3 times. Treating the environment in a light incubator under the following conditions: 25 +/-2 ℃, 16h/8h (L/D) and 80 percent of relative humidity. And 7d, observing the growth condition of the roots and the overall condition of the plants, photographing, measuring the fresh weight, measuring the root length by using Image-Pro Plus 6.0 software, and calculating the root length and the fresh weight inhibition rate. Root length inhibition (%) - (control root length-treated root length)/control root length × 100%; fresh weight inhibition (%) - (control fresh weight-treated fresh weight)/control fresh weight × 100%. The test results are shown in tables 6 and 7.
Example 20: evaluation of herbicidal Activity of some Compounds on Trifolium Pratense
Pre-treatment for pregermination: soaking weed seeds (pseudo-osmyl grass seeds) in 15% sodium hypochlorite for 15min, washing with tap water for several times, and washing with distilled water for 2-3 times. Soaking the seeds of herba Desmodii Styracifolii in 200 mg.L-1Taking out the seeds after 28h from the gibberellin aqueous solution, and washing the seeds for 2-3 times for later use by using distilled water. Qualitative filter paper with a diameter of 9.0cm was placed in a petri dish, and 3mL of distilled water was respectively sucked to uniformly wet the filter paper. 40 ~ 50 of false stinky grass seeds (place the quantity difference according to the size of seed) are evenly placed respectively in every culture dish, and the dropwise add distilled water again until the seed does not float, cover the plastic wrap that pricks the aperture in order to guarantee ventilative and prevent the moisture evaporation. The culture medium is placed in a light incubator with the temperature of 25 +/-2 ℃, the temperature of 16h/8h (L/D) and the relative humidity of 80 percent. And after 2-3 days, selecting the seeds which just expose white for later use.
Experimental treatment: each test compound was dissolved in an appropriate amount of acetone, diluted with water (containing 0.1% TW-80) to a concentration of 10g/L, and further diluted with acetone + water + Tween 80 to 25 mg/L. A plastic cup with the diameter of about 5cm and the height of 7cm is used as a container, 3-4 layers of glass beads with the diameter of about 0.4cm are added into the cup, the glass beads are distributed in the plastic cup, a preservative film with small holes is covered on the plastic cup, the moisture is prevented from evaporating and losing, the air permeability is kept, and 10-15 exposed and white pseudo-odorous grass seeds are placed in each small cup. The control group was treated with an equal volume of acetone in distilled water (typically less than 1% treatment organic solvent), and each treatment was repeated 3 times. Treating the environment in a light incubator under the following conditions: 25 +/-2 ℃, 16h/8h (L/D) and 80 percent of relative humidity. And 7d, observing the growth condition of the roots and the overall condition of the plants, photographing, measuring the fresh weight, measuring the root length by using Image-Pro Plus 6.0 software, and calculating the root length and the fresh weight inhibition rate. Root length inhibition (%) - (control root length-treated root length)/control root length × 100%; fresh weight inhibition (%) - (control fresh weight-treated fresh weight)/control fresh weight × 100%. The test results are shown in tables 6 and 7.
Example 21: evaluation of herbicidal Activity of some Compounds on Eleusine indica
Pre-treatment for germination acceleration: soaking weed seeds (Eleusine indica seeds) in 15% sodium hypochlorite for 15min, washing with tap water for several times, and washing with distilled water for 2-3 times. Soaking herba Eleusines Indicae seed in 200 mg.L-1Taking out the seeds after 28h from the gibberellin aqueous solution, and washing the seeds for 2-3 times for later use by using distilled water. Qualitative filter paper with a diameter of 9.0cm was placed in a petri dish, and 3mL of distilled water was respectively sucked to uniformly wet the filter paper. 40 ~ 50 of goosegrass seeds (place the quantity difference according to the size of seed) are evenly placed respectively to every culture dish, and the dropwise add distilled water again till the seed does not float, cover the plastic wrap that pricks the aperture in order to guarantee ventilative and prevent the evaporation of water. The culture medium is placed in a light incubator with the temperature of 25 +/-2 ℃, the temperature of 16h/8h (L/D) and the relative humidity of 80 percent. And after 2-3 days, selecting the seeds which just expose white for later use.
Experimental treatment: each test compound was dissolved in an appropriate amount of acetone, diluted with water (containing 0.1% TW-80) to a concentration of 10g/L, and further diluted with acetone + water + Tween 80 to 25 mg/L. A plastic cup with the diameter of about 5cm and the height of 7cm is used as a container, 3-4 layers of glass beads with the diameter of about 0.4cm are added into the cup, the glass beads are distributed in the plastic cup, a preservative film with small holes is covered, evaporation and dissipation of water are prevented, ventilation is kept, and 10-15 exposed and white goosegrass seeds are placed in each small cup. The control group was treated with an equal volume of acetone in distilled water (typically less than 1% treatment organic solvent), and each treatment was repeated 3 times. Treating the environment in a light incubator under the following conditions: 25 +/-2 ℃, 16h/8h (L/D) and 80 percent of relative humidity. And 7d, observing the growth condition of the roots and the overall condition of the plants, photographing, measuring the fresh weight, measuring the root length by using Image-Pro Plus 6.0 software, and calculating the root length and the fresh weight inhibition rate. Root length inhibition (%) - (control root length-treated root length)/control root length × 100%; fresh weight inhibition (%) - (control fresh weight-treated fresh weight)/control fresh weight × 100%. The test results are shown in tables 6 and 7.
Example 22: evaluation of herbicidal Activity of part of Compounds on Echinochloa crusgalli
Pre-treatment for pregermination: soaking weed seeds (barnyard grass seeds) in 15% sodium hypochlorite for 15min, washing with tap water for several times, and washing with distilled water for 2-3 times. Then soaking barnyard grass seeds in 200 mg.L-1Taking out the seeds after 28h from the gibberellin aqueous solution, and washing the seeds for 2-3 times for later use by using distilled water. Qualitative filter paper with a diameter of 9.0cm is placed in a culture dish, and 3mL of distilled water is respectively sucked to uniformly wet the filter paper. 40-50 barnyard grass seeds (different in quantity according to the size of the seeds) are uniformly placed in each culture dish respectively, distilled water is dripped again until the seeds do not float, and a preservative film with small holes is covered to ensure ventilation and prevent water evaporation. The culture medium is placed in a light incubator with the temperature of 25 +/-2 ℃, the temperature of 16h/8h (L/D) and the relative humidity of 80 percent. And after 2-3 days, selecting the seeds which just expose white for later use.
Experimental treatment: each test compound was dissolved in an appropriate amount of acetone, diluted with water (containing 0.1% TW-80) to a concentration of 10g/L, and then diluted with acetone + water + Tween 80 to 25 mg/L. A plastic cup with the diameter of about 5cm and the height of 7cm is used as a container, 3-4 layers of glass beads with the diameter of about 0.4cm are added into the cup, the glass beads are distributed in the plastic cup, a preservative film with small holes is covered on the plastic cup, the water is prevented from evaporating and losing, the air permeability is kept, and 10-15 cockspur grass seeds with dew are placed in each small cup. The control group was treated with an equal volume of distilled water containing acetone (typically less than 1% of organic solvent), and each treatment was repeated 3 times. Treating the environment in a light incubator under the following conditions: 25 +/-2 ℃, 16h/8h (L/D) and 80 percent of relative humidity. And 7d, observing the growth condition of the roots and the overall condition of the plants, photographing, measuring the fresh weight, measuring the root length by using Image-Pro Plus 6.0 software, and calculating the root length and the fresh weight inhibition rate. Root length inhibition (%) - (control root length-treated root length)/control root length × 100%; fresh weight inhibition (%) - (control fresh weight-treated fresh weight)/control fresh weight × 100%. The test results are shown in tables 6 and 7.
Table 6: fresh weight inhibition test of partial compounds of the invention on 6 weeds
Figure BDA0003574916350000261
Figure BDA0003574916350000271
Table 7: root length inhibition test of partial compounds of the invention on 6 weeds
Figure BDA0003574916350000272
Figure BDA0003574916350000281
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (10)

1. An N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects is characterized in that the structure is shown as a general formula (A):
Figure FDA0003574916340000011
wherein X is selected from any one of C, N atoms;
in the general formula, the heterocyclic ring which is in phase with the selenourea ring is a nitrogen-containing heterocyclic ring; including any of the following rings: a pyrazine ring, a pyridine ring, a pyrimidine ring, a quinoline ring, a pyridazine ring, an isoquinoline ring, a triazine ring, an imidazole ring, an oxazole ring, a pyrazole ring, an isoxazole ring, a thiazole ring, a purine ring, an isothiazole ring, a pteridine ring, a piperidine ring, a tetrahydropyrazine ring;
when X is N, no R1Substituent, R2Is a substituent group on any position or any atom on the heterocycle, and is mono-substituted, same or different groups of bi-substituted and tri-substituted;
when X ═ C, R1Can be selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C12An alkyl group; r is2Is substituent at any position or atom on the heterocycle, and is mono-substituted, same or different groups of bi-substituted and tri-substituted.
2. The N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects as claimed in claim 1, wherein,
when X is N, no R1Substituent, R2Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C12An alkyl group;
when X ═ C, R1Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C12An alkyl group; r2Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C12An alkyl group.
3. The N-difluoromethyl bis-nitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects as claimed in claim 2, wherein,
when X is N, there is no R1Substituent, R2Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group;
when X ═ C, R1Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group; r2Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C8An alkyl group;
further, the air conditioner is provided with a fan,
when X is N, no R1Substituent, R2Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C4An alkyl group;
when X ═ C, R1Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C4An alkyl group; r2Is hydrogen, fluorine, chlorine, bromine, iodine, methoxy formyl, ethoxy formyl, propoxy formyl, tert-butoxy formyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl or C1-C4An alkyl group.
4. The N-difluoromethyl dinitroheterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects according to claim 3, characterized in that the compounds are compounds D-1 to D-27, and the structures thereof are shown as follows:
Figure FDA0003574916340000021
5. a pharmaceutically acceptable salt of an N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects, which is formed by the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects according to any one of claims 1 to 4 and an acid;
the acid comprises at least one of hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, fumaric acid, sorbic acid, malic acid and citric acid.
6. The preparation method of the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects as claimed in any one of claims 1 to 4, characterized by comprising the following steps:
dissolving dinitrogen heterocyclic compound, selenium powder and alkali with organic solvent, adding 2-bromo-2, 2-difluoroacetate BrCF2CO2Et, sealing, heating for reaction, cooling, extracting, drying and purifying to obtain the N-difluoromethyl dinitrogen heterocyclic selenourea compound with the functions of killing insects, inhibiting bacteria, weeding and resisting cancers; the reaction path is shown as formula (1):
(1)
Figure FDA0003574916340000031
7. the preparation method of N-difluoromethyl dinitroselenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects as claimed in claim 6, wherein,
the alkali comprises at least one of potassium carbonate and potassium tert-butoxide;
the dinitrogen heterocyclic compound, the selenium powder, the 2-bromo-2, 2-difluoroacetate and the alkali are calculated according to a molar ratio of 0.10-0.30: 0.30-0.50: 0.4-0.6: 0.30-0.50;
the organic solvent includes but is not limited to at least one of N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, 1, 4-dioxane and acetone;
the heating reaction conditions are as follows: stirring and reacting in an oil bath kettle at the temperature of 40-120 ℃.
8. A composition with insecticidal, bacteriostatic, herbicidal and anticancer effects, which comprises the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects of any one of claims 1 to 4, and/or the pharmaceutically acceptable salt of the N-difluoromethyl dinitrogen heterocyclic selenourea compound with insecticidal, bacteriostatic, herbicidal and anticancer effects of claim 5.
9. The N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects of any one of claims 1 to 4, the pharmaceutically acceptable salts of the N-difluoromethyl dinitrogen heterocyclic selenourea compounds with insecticidal, bacteriostatic, herbicidal and anticancer effects of claim 5, or the composition with insecticidal, bacteriostatic, herbicidal and anticancer effects of claim 8, for use in preparing insecticidal, bactericidal, herbicidal and anticancer drugs.
10. Use according to claim 9,
the insects include agricultural and/or forestry insects;
the bacteria comprise at least one of deuteromycotina, basidiomycotina, ascomycotina, zygomycotina and flagellates;
the grass comprises at least one of broadleaf, arborescent, cyperaceae, bolting genus, alismatis family, monochoriaceae, scrophulariaceae, lythraceae, and broadleaf weeds;
the anti-cancer drug is a drug capable of inhibiting growth, migration and/or reproduction of cancer cells and/or killing cancer cells;
the cancer cells comprise at least one of human ovarian cancer cells A2780 and human breast cancer cells BT-20.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115650926A (en) * 2022-11-16 2023-01-31 华南农业大学 Azole selenone functional reagent and application thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109020897A (en) * 2018-06-22 2018-12-18 华南农业大学 A kind of azole sulphur (selenium) ketone derivatives and its preparation method and application
CN109369538A (en) * 2018-11-30 2019-02-22 华南农业大学 A kind of N- difluoromethyl azole sulphur (selenium) urea derivative and preparation method thereof
CN111978260A (en) * 2020-07-29 2020-11-24 华南农业大学 Benzimidazolone derivative or agriculturally and pharmaceutically acceptable salt and application thereof
CN112300079A (en) * 2020-11-05 2021-02-02 华南农业大学 N-difluoromethyl azole selenourea derivative or agriculturally and pharmaceutically acceptable salt and application thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109020897A (en) * 2018-06-22 2018-12-18 华南农业大学 A kind of azole sulphur (selenium) ketone derivatives and its preparation method and application
CN109369538A (en) * 2018-11-30 2019-02-22 华南农业大学 A kind of N- difluoromethyl azole sulphur (selenium) urea derivative and preparation method thereof
CN111978260A (en) * 2020-07-29 2020-11-24 华南农业大学 Benzimidazolone derivative or agriculturally and pharmaceutically acceptable salt and application thereof
CN112300079A (en) * 2020-11-05 2021-02-02 华南农业大学 N-difluoromethyl azole selenourea derivative or agriculturally and pharmaceutically acceptable salt and application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115650926A (en) * 2022-11-16 2023-01-31 华南农业大学 Azole selenone functional reagent and application thereof

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