CN102669121B - Application of triazolopyrimidine derivative in preparation of medicine for resisting agricultural fungi - Google Patents
Application of triazolopyrimidine derivative in preparation of medicine for resisting agricultural fungi Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000003814 drug Substances 0.000 title claims abstract description 14
- 241000233866 Fungi Species 0.000 title claims abstract description 8
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical class BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 title abstract 3
- -1 nitro, methoxyl Chemical group 0.000 claims abstract description 17
- 241000223221 Fusarium oxysporum Species 0.000 claims abstract description 11
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 150000008523 triazolopyridines Chemical class 0.000 claims description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 22
- 241000894006 Bacteria Species 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 230000001857 anti-mycotic effect Effects 0.000 claims description 8
- 239000002543 antimycotic Substances 0.000 claims description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 241000813090 Rhizoctonia solani Species 0.000 claims description 6
- 206010039509 Scab Diseases 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- XAYCTBDPZIKHCW-UHFFFAOYSA-N (3-chloropyridin-2-yl)hydrazine Chemical compound NNC1=NC=CC=C1Cl XAYCTBDPZIKHCW-UHFFFAOYSA-N 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 244000299906 Cucumis sativus var. sativus Species 0.000 claims 1
- 240000008067 Cucumis sativus Species 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 240000007594 Oryza sativa Species 0.000 abstract description 3
- 235000007164 Oryza sativa Nutrition 0.000 abstract description 3
- 241000221696 Sclerotinia sclerotiorum Species 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 235000009566 rice Nutrition 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract 4
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- 241000633856 Mycosphaerella pomi Species 0.000 abstract 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 abstract 1
- 238000012216 screening Methods 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 9
- 239000002609 medium Substances 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 238000011160 research Methods 0.000 description 6
- 150000003852 triazoles Chemical group 0.000 description 6
- 239000013641 positive control Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000575 pesticide Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000003905 agrochemical Substances 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000001965 potato dextrose agar Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000009333 weeding Methods 0.000 description 3
- ATCRIUVQKHMXSH-UHFFFAOYSA-N 2,4-dichlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1Cl ATCRIUVQKHMXSH-UHFFFAOYSA-N 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
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- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
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- 230000012010 growth Effects 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
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- 239000002054 inoculum Substances 0.000 description 2
- 239000006101 laboratory sample Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 2
- 235000010603 pastilles Nutrition 0.000 description 2
- UDEWPOVQBGFNGE-UHFFFAOYSA-N propyl benzoate Chemical compound CCCOC(=O)C1=CC=CC=C1 UDEWPOVQBGFNGE-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- SODPIMGUZLOIPE-UHFFFAOYSA-N (4-chlorophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1 SODPIMGUZLOIPE-UHFFFAOYSA-N 0.000 description 1
- 0 *c1nnc2[n]1cccc2Cl Chemical compound *c1nnc2[n]1cccc2Cl 0.000 description 1
- MXNBDFWNYRNIBH-UHFFFAOYSA-N 3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1 MXNBDFWNYRNIBH-UHFFFAOYSA-N 0.000 description 1
- AFPHTEQTJZKQAQ-UHFFFAOYSA-N 3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1 AFPHTEQTJZKQAQ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 1
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- KDVYCTOWXSLNNI-UHFFFAOYSA-N 4-t-Butylbenzoic acid Chemical compound CC(C)(C)C1=CC=C(C(O)=O)C=C1 KDVYCTOWXSLNNI-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000412366 Alternaria mali Species 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 241001225321 Aspergillus fumigatus Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- TWFZGCMQGLPBSX-UHFFFAOYSA-N Carbendazim Natural products C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical compound COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940091771 aspergillus fumigatus Drugs 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- JNPZQRQPIHJYNM-UHFFFAOYSA-N carbendazim Chemical compound C1=C[CH]C2=NC(NC(=O)OC)=NC2=C1 JNPZQRQPIHJYNM-UHFFFAOYSA-N 0.000 description 1
- 239000006013 carbendazim Substances 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- CCMGSHLZTIQYKA-UHFFFAOYSA-N formic acid pentylbenzene Chemical compound C(=O)O.C(CCCC)C1=CC=CC=C1 CCMGSHLZTIQYKA-UHFFFAOYSA-N 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
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- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses the application of triazolopyrimidine derivative shown in formula (I) in the preparation of medicine for resisting agricultural fungi. The triazolopyrimidine derivative has inhibitory action for cylindrosporium pomi brooks, cucumber sclerotinia sclerotiorum, rice sheath blight disease, fusarium nivale or fusarium oxysporum, wherein the inhibition ratio for the fusarium nivale reaches 49.8%, the inhibition ratio for the fusarium oxysporum reaches 66.7%, the inhibition ratio for the cylindrosporium pomi brooks or cucumber sclerotinia sclerotiorum reaches 100%; and the inhibition ratio for the rice sheath blight disease reaches 66.7%. The invention provides a new variety for screening the medicine for resisting fungi; and in the formula (I), R is C1-C4 alkyl or substituent phenyl, and the substituent group on the substituent phenyl is methyl, nitro, methoxyl, chloride ion or fluorine ion.
Description
(1) technical field
The present invention relates to the application of a kind of triazolopyridine derivatives in the anti-agriculture fungi-medicine of preparation.
(2) background technology
In agricultural chemical compound newly developed, nearly 90 percent pesticide species contains the compound of heterocycle, and nitrogen heterocyclic ring has occupied major part, and this has opened up wide development space for the development of agricultural chemicals.Nitrogen-containing heterocycle compound is very little to warm blooded animal toxicity, and especially the toxicity to birds and fish is very low, and has excellent biologically active, such as super-high-efficient activity of weeding, insecticidal activity, bactericidal activity etc.In numerous nitrogen-containing heterocycle compounds, triazole ring, pyridine rings etc. are because of its unique architectural feature, good biologically active and to characteristics such as human body low toxicities, and are significant in novel pesticide initiative research, become one of study hotspot of current environment friendly agricultural.
Pyridine is the biological isostere of phenyl ring, to phenyl ring similar structure and character is arranged, because pyridine ring has preferably interior absorption, and cyclosubstituted the significantly improving of the corresponding benzene of its biological activity ratio, and toxicity reduces greatly.Thereby pyridine farm chemical has had significant progress after entering the nineties, has been penetrated in each application branch and structure type of agricultural chemicals.The compound of 1,2,4-triazole has broad-spectrum biological activity equally, such as sterilization, weeding, coordinate plant growth, anticancer etc.Since first triazole type efficient germicide triazolone came out, triazole class compounds was one of hot subject of pesticide research always, had developed so far the triazole bactericidal agent of tens kinds of efficient, low toxicities.
A plurality ofly heterocyclic fusedly often can realize its bioactive stack and widen drug effect spectrum in a part, it is of common occurrence that this type of is reported in document.In Pesticide Science research, the triazole fused heterocyclic compound that contains pyridine structure is actually rare, simultaneously because unique physiologically active of triazole fused heterocyclic compound has obtained extensive concern, such as sterilization, weeding, anticancer etc.
(3) summary of the invention
The object of the invention provides the new application of a kind of triazolopyridine derivatives, i.e. application in the anti-agriculture fungi-medicine of preparation.
The technical solution used in the present invention is:
The application of triazolopyridine derivatives shown in a kind of formula (I) in the anti-agriculture fungi-medicine of preparation,
R is alkyl or the substituted-phenyl of C1～C4 in the formula (I), and the substituting group on the described substituted-phenyl is methyl, nitro, methoxyl group, chlorine atom or fluorine atom.
Further, it is one of following that described R is preferably: m-methyl benzoic acid, m-Nitrobenzoic Acid, m-fluorobenzoic acid, m-chlorobenzoic acid, o-methoxybenzoic acid, P-methoxybenzoic acid, to amylbenzene formic acid, p-tert-butyl benzoic acid, n-propyl benzoate, cumfrey, p-chlorophenoxyacetic acid, paranitrobenzoic acid, 2,4-dichlorobenzoic acid, o-toluic acid, p-methylbenzoic acid, 0-chloro-benzoic acid, parafluorobenzoic acid, formic acid, acetic acid, trifluoroacetic acid or propionic acid.
Further, described agriculture fungi is one of following or more than one combination: avenge that rotten reaping hook is mould, Fusarium oxysporum, apple scab bacterium, cucumber sclerotiorum or Rhizoctonia solani Kuhn.
Further, triazolopyridine derivatives of the present invention is preferably one of following:
Further, being applied as in the anti-agriculture fungi-medicine of preparation of triazolopyridine derivatives shown in the described formula (I): triazolopyridine derivatives shown in the formula (I) is dissolved in the organic solvent, make the antimycotic inhibitor of 10～50mol/L, the antimycotic inhibitor of preferred 20mol/L; Described organic solvent is dimethyl sulfoxide (DMSO) (DMSO) or dimethyl formamide (DMF), preferred DMSO.
Further, triazolopyridine derivatives prepares as follows shown in the formula (I): with the acid shown in the 2-diazanyl shown in the formula (II)-3-chloropyridine and the formula (III) at phosphorus oxychloride (POCl
3) in, under 140 ℃, 60W condition, carry out microwave ring closure reaction 15min, reaction finishes, reactant liquor is poured into water, and extracts with ethyl acetate again, merges organic layer, dry, concentrated, residue with known method column chromatography or recrystallization method separates and purifying for example, is obtained the target product triazolopyridine derivatives; Column chromatography or recrystallization solvent for use are one or more the mixed solution in benzinum, ethyl acetate, n-hexane or the ethanol; Described 2-diazanyl-3-chloropyridine: acid: the ratio of the amount of substance that feeds intake of phosphorus oxychloride is 1:1.0～1.5:2～20;
R is alkyl or the substituted-phenyl of C1～C4 in the formula (III), and the substituting group in the described substituted-phenyl on the phenyl is methyl, nitro, methoxyl group, chlorine atom or fluorine atom.
Above-mentioned preparation method's chemical equation is:
Compared with prior art, beneficial effect of the present invention is mainly reflected in: triazolopyridine derivatives of the present invention is mould or Fusarium oxysporum is inhibited to the rotten reaping hook of apple scab bacterium, cucumber sclerotiorum, Rhizoctonia solani Kuhn, snow, reach 49.8% to avenging the mould inhibiting rate of rotten reaping hook, the Fusarium oxysporum inhibiting rate is reached 66.76%, apple scab bacterium or cucumber sclerotiorum inhibiting rate are reached 100%, the Rhizoctonia solani Kuhn inhibiting rate is reached 66.7%, and the present invention provides new kind for the antifungal drug screening.
(4) description of drawings
Fig. 1 avenges mould active testing 96 orifice plates of the mould and sharp spore reaping hook of rotten reaping hook and adds master drawing, and B2 is the blank hole to D2, and E2 is to the negative control wells of G2, and B3 is to D3 positive control hole not, and one group in per three holes add sample from E3 to H11.
(5) embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
The preparation of triazolopyridine derivatives of the present invention (I-1)～(I-14) is referring to patent application 201110066188.6.
Embodiment 1
1) preparation of antimycotic inhibitor
Triazolopyridine derivatives (I-1)～(I-14) used respectively dimethyl sulfoxide (DMSO) (DMSO) dissolving, be mixed with respectively the reagent agent 1～14 of 20mol/L.
2) apple scab bacterium, cucumber sclerotiorum and rice sheath blight disease thalli growth rate determination method (mycelium growth rate test)
The reagent agent 1～14 of step 1) preparation is mixed with respectively 50 μ g/mL liquids 1～14 with DMSO respectively under aseptic condition, then respectively drawing the 1mL liquid injects in the culture dish, add respectively again the 9mL agar medium, make pastille flat board 1～14 after shaking up, do blank with the flat board that adds 1mL sterilization DMSO.
With apple scab bacterium (latin name Alternaria mali, Shandong Scientific Research Academy, source Institute of Micro-biology), cucumber sclerotiorum (latin name Sclerotinia sclerotiorum (Lib.) de Bary, Shandong Scientific Research Academy, source Institute of Micro-biology) and Rhizoctonia solani Kuhn (latin name Rhizoctonia solani, Shandong Scientific Research Academy, source Institute of Micro-biology) is inoculated in respectively on the agar medium flat board, cultivate 72h for 25 ℃, obtain to contain the flat board of mycelia.
Card punch with diameter 4mm cuts the bacterium dish along above-mentioned mycelia outer rim, moves to respectively on the pastille flat board 1～14.Every processing triplicate.Culture dish is placed on cultivation in 24 ± 1 ℃ of constant incubators.Measure after 72 hours and respectively process bacterium dish expansion diameter, average, relatively calculate relative bacteriostasis rate with blank, the results are shown in Table shown in 1.
3) the mould active testing of the mould and sharp spore reaping hook of the rotten reaping hook of snow adopts the antimycotic sensitivity experiments method of standardization of American National standard committee of clinical labororatory (NC-CLS) recommendation
Avenge rotten reaping hook mould (CGMCC3.2830) and take from Chinese common micro-organisms culture presevation administrative center (CGMCC), and grow at potato dextrose agar (PDA) medium; Fusarium oxysporum (FGSC A1100) is taken from genetic of fungi and learns the stock center, and cultivates at the RPMI1640 medium.Under 28 ℃, above-mentioned two kinds of target bacterial classifications (avenge rotten reaping hook is mould, Fusarium oxysporum) were being cultivated 48 hours in the culture fluid separately, and made fungal spore suspension finally reach 104 mycelia/milliliters.
A: material and method
Tested bacterial classification (fungi):
Avenge rotten reaping hook mould (CGMCC3.2830), Fusarium oxysporum (FGSC A1100)
Medium:
Detect medium (PDB): 200g potato, 20g glucose, 1000mL water
Equipment:
The aseptic round bottom microwell plate in 96 holes;
Multi-functional microplate reader TECAN GENios plus;
B: experimental technique:
1. the preparation of target bacterium bacteria suspension:
Avenge rotten reaping hook mould (CGMCC3.2830), Fusarium oxysporum (FGSC A1100)
28 ℃ of cultivation 7d cause the generation spore in the PDA plating medium.
2. the calculating of target bacterium inoculum density:
Use blood counting chamber to calculate cell number:
Cell concentration=every lattice cell number * 4 * 10
6Cfu/mL
Avenge rotten reaping hook mould (CGMCC3.2830), Fusarium oxysporum (FGSC A1100)
Inoculum density=0.5 – 2.5 * 10
4Cfu/mL
3. the preparation of test sample:
Accurately take by weighing 0.5mg triazolopyridine derivatives (I-1)～(I-14) and be transferred to the dried rear 50 μ gDMSO of adding of volatilization in the 96 hole shallow bore hole plates, be made into 10mg/mL solution.
4. positive control:
Respectively amphotericin B, carbendazim are dissolved in DMSO and are made into the 6.4mg/mL solvent.
5. detection wavelength:
Aspergillus fumigatus and Candida albicans adopt the utilizing emitted light of 544nm exciting light and 595nm to detect bacteriostatic activity.
6.96 the preparation of orifice plate:
By the table * * shown in mode in 96 orifice bores, add sample, medium, bacteria suspension and indicator.
The antimycotic laboratory sample concentration of table 1.
The anti-phytopathogen laboratory sample of table 2. volume
| ? | The blank hole | Negative control hole | The positive control hole | Sample well |
| Medium | 190μL | ? | ? | ? |
| Bacteria suspension | ? | 190μL | 190μL | 190μL |
| Sample | ? | ? | ? | 1μL |
| Positive control | ? | ? | 1μL | ? |
| Indicator | 10μL | 10μL | 10μL | 10μL |
7. active result's calculating is in judgement:
As shown in Figure 1, B2 is the blank hole to D2, and E2 is to the negative control wells of G2, and B3 is to D3 positive control hole not, and one group in per three holes add sample from E3 to H11, and active testing result is calculated by following formula, the results are shown in Table shown in 3:
Sample activity=[1 – (OD
Sample– OD
Background)/(OD
Negative– OD
Background)] * 100%
OD
SampleBe absorption of sample light (utilizing emitted light) value
OD
BackgroundFor blank absorbs light (utilizing emitted light) value
OD
NegativeNegative contrast absorbs light (utilizing emitted light) value
The antimycotic inhibitor of table 3 is to the inhibiting rate of fungi
Numerical value is not measured in "-" expression in the table 1.
Claims (6)
1. the application of triazolopyridine derivatives shown in the formula (I) in the anti-agriculture fungi-medicine of preparation,
R is substituted-phenyl in the formula (I), and the substituting group on the described substituted-phenyl is methyl, nitro, methoxyl group, chlorine atom or fluorine atom.
2. the application of triazolopyridine derivatives as claimed in claim 1 in the anti-agriculture fungi-medicine of preparation, it is characterized in that, described agriculture fungi is one of following or more than one combination: avenge that rotten reaping hook is mould, Fusarium oxysporum, apple scab bacterium, cucumber sclerotiorum or Rhizoctonia solani Kuhn.
3. triazolopyridine derivatives as claimed in claim 1 is in the application of preparation in the anti-agriculture fungi-medicine, it is characterized in that described triazolopyridine derivatives is one of following:
4. the application of triazolopyridine derivatives as claimed in claim 2 in the anti-agriculture fungi-medicine of preparation, it is characterized in that described being applied as: triazolopyridine derivatives shown in the formula (I) is dissolved in the organic solvent, makes the antimycotic inhibitor of 10～50mol/L; Described organic solvent is dimethyl sulfoxide (DMSO) or dimethyl formamide.
5. the application of triazolopyridine derivatives as claimed in claim 4 in the anti-agriculture fungi-medicine of preparation is characterized in that described antimycotic inhibitor concentration is 20mol/L.
6. the application of triazolopyridine derivatives as claimed in claim 1 in the anti-agriculture fungi-medicine of preparation, it is characterized in that triazolopyridine derivatives prepares as follows shown in the formula (I): with the acid shown in the 2-diazanyl shown in the formula (II)-3-chloropyridine and the formula (III) in phosphorus oxychloride, in 140 ℃, carry out microwave ring closure reaction 15min under the 60W condition, reaction finishes, reactant liquor is poured into water, extract with ethyl acetate again, merge organic layer, dry, concentrated, residue is separated and purifying with column chromatography or recrystallization method, obtain the target product triazolopyridine derivatives; Column chromatography or recrystallization solvent for use are one or more the mixed solution in benzinum, ethyl acetate, n-hexane or the ethanol; Described 2-diazanyl-3-chloropyridine: acid: the ratio of the amount of substance that feeds intake of phosphorus oxychloride is 1:1.0～1.5:2～20;
R is substituted-phenyl in the formula (III), and the substituting group in the described substituted-phenyl on the phenyl is methyl, nitro, methoxyl group, chlorine atom or fluorine atom.
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Application publication date: 20120919 Assignee: Hangzhou Guangyoujiu Enterprise Management Partnership (L.P.) Assignor: JIANG University OF TECHNOLOGY Contract record no.: X2023980033595 Denomination of invention: Application of a triazole pyridine derivative in the preparation of anti agricultural fungal drugs Granted publication date: 20131016 License type: Common License Record date: 20230316 Application publication date: 20120919 Assignee: Hangzhou Zhiguo Enterprise Service Co.,Ltd. Assignor: JIANG University OF TECHNOLOGY Contract record no.: X2023980033596 Denomination of invention: Application of a triazole pyridine derivative in the preparation of anti agricultural fungal drugs Granted publication date: 20131016 License type: Common License Record date: 20230316 Application publication date: 20120919 Assignee: Hangzhou baibeiyou Biotechnology Co.,Ltd. Assignor: JIANG University OF TECHNOLOGY Contract record no.: X2023980033594 Denomination of invention: Application of a triazole pyridine derivative in the preparation of anti agricultural fungal drugs Granted publication date: 20131016 License type: Common License Record date: 20230315 |
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