CN107459493A - Diclazuril derivative and its application and the bactericide containing the derivative - Google Patents

Diclazuril derivative and its application and the bactericide containing the derivative Download PDF

Info

Publication number
CN107459493A
CN107459493A CN201610387500.4A CN201610387500A CN107459493A CN 107459493 A CN107459493 A CN 107459493A CN 201610387500 A CN201610387500 A CN 201610387500A CN 107459493 A CN107459493 A CN 107459493A
Authority
CN
China
Prior art keywords
compound
formula
group
derivative
tert
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201610387500.4A
Other languages
Chinese (zh)
Other versions
CN107459493B (en
Inventor
杨光富
熊力
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huazhong Normal University
Original Assignee
Huazhong Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Huazhong Normal University filed Critical Huazhong Normal University
Priority to CN201910420685.8A priority Critical patent/CN110183386B/en
Priority to CN201610387500.4A priority patent/CN107459493B/en
Publication of CN107459493A publication Critical patent/CN107459493A/en
Application granted granted Critical
Publication of CN107459493B publication Critical patent/CN107459493B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/553—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention relates to pesticide field, a kind of diclazuril derivative and its application and the bactericide containing the derivative are disclosed, the derivative has formula (1) or the structure shown in formula (2).Foregoing diclazuril derivative provided by the invention can be employed as mitochondrial succinate dehydrogenase inhibitor, and there is plant epiphyte resisting disease, more specifically, the foregoing diclazuril derivative of the present invention can be used in preventing and treating rice sheath blight disease, gray mold of cucumber, cucumber downy mildew and powdery mildew of cucumber etc..

Description

Diclazuril derivative and its application and the bactericide containing the derivative
Technical field
The present invention relates to pesticide field, in particular it relates to which a kind of diclazuril derivative, diclazuril derivative are as line Application and one kind of the application, diclazuril derivative of plastochondria succinate dehydrogenase inhibitors in plant epiphyte resisting disease are used for The bactericide of plant epiphyte resisting disease.
Background technology
Global bactericide sales volume accounts for the 26.3% of global pesticide sales volume within 2012, has reached 140.1 hundred million dollars, wherein Bactericide using succinate dehydrogenase as target reached 20% in the growth rate of 2012, was the most fast a kind of sterilization of speedup Agent, account for the 5.4% of total bactericide market share.This series bactericidal agent has the efficient, bactericidal activity of wide spectrum and relatively low resistance The advantages that risk, it is one of current most promising bactericide.
But existing commercialization succinate dehydrogenase inhibitors series bactericidal agent belongs to amide-type, this series bactericidal agent Structurally and functionally in mechanism it is all similar, therefore this kind of compound is faced with higher resistance risk.So as to which searching has The succinate dehydrogenase inhibitors of brand-new skeleton have very important significance.
Diclazuril (Diclazuril) be by Belgian Yang Sen companies 1986 report coccidiostat, in structure On belong to triazine benzene acetonitrile class compound, the coccidiosis for birds.Diclazuril is mainly used in the preventing and treating of chicken coccidiasis, category In efficient coccidiostat, while also have the advantages that wide spectrum, low toxicity, drug resistance are low and dosage is small.Clinical test proves, ground Gram pearl profit has good effect to el pato worm and rabbit coccidia etc., at the same the coccidia that other medicines are produced with drug resistance also have it is non- Often good effect, has been had more than 40 countries and corresponding disease is prevented and treated using diclazuril in the world at present.
The current mechanism of action of diclazuril is still not clear, and the research to its mechanism of action at present is based only on cell and Asia Cellular level.Taylor etc. report diclazuril to infect lamb Eimeria the first generation and second generation segmenta and The gametophyte stage is effective, and it can also influence the synthesis of coccidia nucleic acid.
The content of the invention
According to the research to diclazuril, there is mitochondrial succinate dehydrogenase inhibitory action the invention provides a series of Diclazuril derivative, there is diclazuril derivative provided by the invention obvious mitochondrial succinate dehydrogenase to suppress The effect of activity and plant epiphyte resisting disease.
To achieve these goals, in a first aspect, the present invention provides a kind of diclazuril derivative, the derivative has formula (1) or the structure shown in formula (2),
Wherein, in formula (1) and formula (2),
R11And R12It is respectively selected from H, C1-4Alkyl, C1-4Alkoxy, halogen, nitro, cyano group, a bromomethyl, a chlorine For methyl, a fluoromethyl, trifluoromethyl and trifluoromethoxy；
R21、R22、R23And R24It is respectively selected from H, C1-4Alkyl, C1-4Alkoxy and halogen；
R3Selected from H, C1-6Alkyl, C1-6Haloalkyl, C1-6Alkoxy, C1-6Halogenated alkoxy, C1-6Alkane sulphur Base, C1-6At least one of halogenated alkylthio, nitro, cyano group and halogen；
And in formula (1), W be O orAnd
Work as R11、R21And R24For H, R22And R23For Cl, when W is O；R3It is not 4-Cl or 4-OCH3。
Second aspect, the present invention provide foregoing diclazuril derivative answering as mitochondrial succinate dehydrogenase inhibitor With.
The third aspect, the present invention provide application of the foregoing diclazuril derivative in plant epiphyte resisting disease.
Fourth aspect, the present invention provide a kind of bactericide for plant epiphyte resisting disease, and the active component of the bactericide is At least one of foregoing diclazuril derivative of the present invention, with the gross weight meter of the bactericide, the active component Content is 0.1-100 weight %.
The diclazuril derivative of the foregoing offer of the present invention can be used as mitochondrial succinate dehydrogenase inhibitor to be used to resist In plant mycosis.
Other features and advantages of the present invention will be described in detail in subsequent specific embodiment part.
Embodiment
The embodiment of the present invention is described in detail below.It is it should be appreciated that described herein specific Embodiment is merely to illustrate and explain the present invention, and is not intended to limit the invention.
The end points of disclosed scope and any value are not limited to the accurate scope or value herein, these scopes or Value should be understood to comprising the value close to these scopes or value.For number range, between the endpoint value of each scope, respectively It can be combined with each other between the endpoint value of individual scope and single point value, and individually between point value and obtain one or more New number range, these number ranges should be considered as specific open herein.
In a first aspect, the invention provides a kind of diclazuril derivative, the derivative has shown in formula (1) or formula (2) Structure,
Wherein, in formula (1) and formula (2),
R11And R12It is respectively selected from H, C1-4Alkyl, C1-4Alkoxy, halogen, nitro, cyano group, a bromomethyl, a chlorine For methyl, a fluoromethyl, trifluoromethyl and trifluoromethoxy；
R21、R22、R23And R24It is respectively selected from H, C1-4Alkyl, C1-4Alkoxy and halogen；
R3Selected from H, C1-6Alkyl, C1-6Haloalkyl, C1-6Alkoxy, C1-6Halogenated alkoxy, C1-6Alkane sulphur Base, C1-6At least one of halogenated alkylthio, nitro, cyano group and halogen；
And in formula (1), W be O orAnd
Work as R11、R21And R24For H, R22And R23For Cl, when W is O；R3It is not 4-Cl or 4-OCH3。
" the C1-4Alkyl " represent the total number of carbon atoms be 1-4 alkyl.
" the C1-4Alkoxy " represent the total number of carbon atoms be 1-4 alkoxy.
" the C1-6Alkyl " represent the total number of carbon atoms be 1-6 alkyl.
" the C1-6Haloalkyl " represent the alkyl that the total number of carbon atoms is 1-6, and at least one hydrogen atom quilt in alkyl Halogen atom substitutes.
" the C1-6Alkoxy " represent the total number of carbon atoms be 1-6 alkoxy.
" the C1-6Halogenated alkoxy " represent the alkoxy that the total number of carbon atoms is 1-6, and at least one hydrogen in alkoxy Atom is substituted by halogen atom.
" the C1-6Alkylthio group " represent the total number of carbon atoms be 1-6 alkylthio group.
" the C1-6Halogenated alkylthio " represent the alkylthio group that the total number of carbon atoms is 1-6, and at least one hydrogen in alkylthio group Atom is substituted by halogen atom.
" halogen " or " halogen atom " include any one or more in fluorine, chlorine, bromine and iodine.
Preferably, in formula (1) and formula (2), R11And R12It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, positive fourth Base, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, Fluorine, chlorine, bromine, nitro, cyano group, a bromomethyl, a chloromethyl, a fluoromethyl, trifluoromethyl and trifluoromethoxy；It is more excellent Choosing
R11And R12Be respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, Ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, fluorine, chlorine, bromine, trifluoromethyl and fluoroform Epoxide；Particularly preferably
R11And R12It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group and fluoroform Base.
Preferably, in formula (1) and formula (2), R21、R22、R23And R24It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl Base, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, uncle Butoxy, fluorine, chlorine and bromine；More preferably
R21、R22、R23And R24Be respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group and Chlorine；Particularly preferably
R21、R22、R23And R24It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl and chlorine.
Preferably, R3Selected from H, C1-4Alkyl, C1-4Haloalkyl, C1-4Alkoxy, C1-4Halogenated alkoxy, C1-4Alkylthio group, C1-4At least one of halogenated alkylthio, nitro, cyano group and halogen；More preferably
R3Selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, just Propoxyl group, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, methyl mercapto, ethylmercapto group, positive rosickyite base, isopropyisulfanyl, just At least one of butylthio, isobutylthio, tertiary butylthio, nitro, cyano group and halogen；Particularly preferably
R3Selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, just Propoxyl group, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, methyl mercapto, ethylmercapto group, positive rosickyite base, isopropyisulfanyl, just At least one of butylthio, isobutylthio, tertiary butylthio, nitro, cyano group and halogen.
For the diclazuril derivative of the structure shown in the formula (1) or formula (2) of the present invention, the present invention provides following several Specific embodiment：
Embodiment 1：In formula (1) and formula (2),
R11And R12Be respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, Ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, fluorine, chlorine, bromine, nitro, cyano group, a bromo Methyl, a chloromethyl, a fluoromethyl, trifluoromethyl and trifluoromethoxy；
R21、R22、R23And R24Be respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, Methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, fluorine, chlorine and bromine；
R3Selected from H, C1-4Alkyl, C1-4Haloalkyl, C1-4Alkoxy, C1-4Halogenated alkoxy, C1-4Alkane sulphur Base, C1-4At least one of halogenated alkylthio, nitro, cyano group and halogen；And work as R11、R21And R24For H, R22And R23For When Cl, W are O；R3It is not 4-Cl or 4-OCH3。
Embodiment 2：In formula (1) and formula (2),
R11And R12Be respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, Ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, fluorine, chlorine, bromine, trifluoromethyl and fluoroform Epoxide；
R21、R22、R23And R24Be respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group and Chlorine；
R3Selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, just Propoxyl group, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, methyl mercapto, ethylmercapto group, positive rosickyite base, isopropyisulfanyl, just At least one of butylthio, isobutylthio, tertiary butylthio, nitro, cyano group and halogen；And
Work as R11、R21And R24For H, R22And R23For Cl, when W is O；R3It is not 4-Cl or 4-OCH3。
Embodiment 3：In formula (1) and formula (2),
R11And R12It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group and fluoroform Base；
R21、R22、R23And R24It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl and chlorine；
R3Selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, just Propoxyl group, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, methyl mercapto, ethylmercapto group, positive rosickyite base, isopropyisulfanyl, just At least one of butylthio, isobutylthio, tertiary butylthio, nitro, cyano group and halogen；And
Work as R11、R21And R24For H, R22And R23For Cl, when W is O；R3It is not 4-Cl or 4-OCH3。
Embodiment 4：The diclazuril derivative is at least one of following compound；And compound A1- A28 and compound B-11-B16 has the structure shown in formula (1)；Compound C1-C12 has the structure shown in formula (2)；
Compound A1：R11、R21And R24For H；R22And R23For Cl；R3For 2-Cl；W is O；
Compound A2：R11、R21And R24For H；R22And R23For Cl；R3For 2-Br；W is O；
Compound A-13：R11、R21And R24For H；R22And R23For Cl；R3For 2-SCH3；W is O；
Compound A4：R11、R21And R24For H；R22And R23For Cl；R3For 3-C2H5；W is O；
Compound A-45：R11、R21And R24For H；R22And R23For Cl；R3For 4-F；W is O；
Compound A6：R11、R21And R24For H；R22And R23For Cl；R3For 4-tC4H9；W is O；
Compound A7：R11、R21And R24For H；R22And R23For Cl；R3For 2,4- (tC4H9)2；W is O；
Compound A-28：R11、R21And R24For H；R22And R23For Cl；R3For 2-Cl-4-tC4H9；W is O；
Compound A9：R11、R21And R24For H；R22And R23For Cl；R3For 2-Br-4-tC4H9；W is O；
Compound A10：R11、R21And R24For H；R22And R23For Cl；R3For 2-CH3-4-tC4H9；W is O；
Compound A11：R11、R21And R24For H；R22And R23For Cl；R3For 3,5- (CH3)2；W is O；
Compound A12：R11、R21And R24For H；R22And R23For Cl；R3For 2,6-Cl2；W is O；
Compound A13：R11、R21And R24For H；R22And R23For Cl；R3For 2,5-Cl2；W is O；
Compound A14：R11、R21And R24For H；R22And R23For Cl；R3For 2,4,6-Cl3；W is O；
Compound A15：R11、R21And R24For H；R22And R23For Cl；R3For 3,4- (CH3)2；W is O；
Compound A16：R11、R21And R24For H；R22And R23For Cl；R3For 2,3-F2；W is O；
Compound A17：R11、R21And R24For H；R22And R23For Cl；R3For 3-Br-4-F；W is O；
Compound A18：R11、R21And R24For H；R22And R23For Cl；R3For 2-CH3-5-F；W is O；
Compound A19：R11、R21And R24For H；R22And R23For Cl；R3For 2-Cl-4-CH3；W is O；
Compound A20：R11、R21And R24For H；R22And R23For Cl；R3For 3,4-Cl2；W is O；
Compound A21：R11For CH3；R21And R24For H；R22And R23For Cl；R3For 2-Cl；W is O；
Compound A22：R11FortC4H9；R21And R24For H；R22And R23For Cl；R3For 2-Br；W is O；
Compound A23：R11For CF3；R21And R24For H；R22For CH3；R23For Cl；R3For 2-SCH3；W is O；
Compound A24：R11For H；R21And R24For CH3；R22And R23For Cl；R3For 2-Cl；W is O；
Compound A25：R11And R23For H；R21For CH3；R22For Cl；R24ForiCH(CH3)2；R3For 2-Br；W is O；
Compound A26：R11、R21、R22And R24For H；R23For Cl；R3For 2-NO2；W is O；
Compound B-11：R11、R21、R23And R24For H；R22For Cl；R3For 4-Cl；W is
Compound B2：R11、R21、R23And R24For H；R22For Cl；R3For 2-Cl；W is
Compound B3：R11、R21、R23And R24For H；R22For Cl；R3For 3,5- (CH3)2；W is
Compound B4：R11、R21、R23And R24For H；R22For Cl；R3For 2-CH3-5-iCH(CH3)2；W is
Compound B5：R11、R21、R23And R24For H；R22For Cl；R3For 2-SCH3；W is
Compound B-26：R11、R21、R23And R24For H；R22For Cl；R3For 4-CH3；W is
Compound B7：R11、R21、R23And R24For H；R22For Cl；R3For 2-CH3-5-F；W is
Compound B8：R11、R21、R23And R24For H；R22For Cl；R3For 3,4- (CH3)2；W is
Compound B9：R11、R21、R23And R24For H；R22For Cl；R3For 2,5-Cl2；W is
Compound B-11 0：R11、R21、R23And R24For H；R22For Cl；R3For 2-Cl-4-F；W is
Compound B-11 1：R11For CH3；R21、R23And R24For H；R22For Cl；R3For 4-Cl；W is
Compound B-11 2：R11ForiCH(CH3)2；R21、R23And R24For H；R22For Cl；R3For 3,5- (CH3)2；W is
Compound B-11 3：R11For CF3；R21、R23And R24For H；R22For Cl；R3For 2-SCH3；W is
Compound B-11 4：R11And R23For H；R21And R24For CH3；R22For Cl；R3For 2-Cl；W is
Compound B-11 5：R11And R23For H；R21For CH3；R22For Cl；R24ForiCH(CH3)2；R3For 2-Br；W is
Compound B-11 6：R11、R21And R24For H；R22And R23For Cl；R3For 2-NO2；W is
Compound C1：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2-Cl-4-CH3；
Compound C2：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,5-Cl2；
Compound C3：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2-Cl；
Compound C4：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,3-F2；
Compound C5：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 3-CH3；
Compound C6：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,4- (tC4H9)2；
Compound C7：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,6-Cl2；
Compound C8：R11、R21And R24For H；R12For ClCH2；R22And R23For Cl；R3For 4-tC4H9；
Compound C9：R11For C2H5；R12、R22And R23For Cl；R21And R24For H；R3For 4-CN；
Compound C10：R11And R24For H；R12For CN；R21For CH3；R22And R23For Cl；R3For 2,4,6-Cl3；
Compound C11：R11、R21、R23And R24For H；R12For NO2；R22For Cl；R3For 2-Cl-4-tC4H9；
Compound C12：R11、R22And R24For H；R12And R21For CH3；R23For Cl；R3For 2-CH3-4-tC4H9。
It should be strongly noted that in above-claimed cpd, on R3Substituent, such as in compound A-28, " R3For 2, 4-(tC4H9)2" represent there is one on 2 and 4tC4H9Substituent；Such as in compound A9, " R3For 2-Cl-4-tC4H9" represent there is a chlorine atom substituent and one respectively on 2 and 4tC4H9Substituent, remaining is similarly.
Second aspect, the invention provides foregoing diclazuril derivative as mitochondrial succinate dehydrogenase inhibitor Using.
The third aspect, the invention provides application of the foregoing diclazuril derivative in plant epiphyte resisting disease.
In the second aspect of the present invention and the third aspect, involved diclazuril derivative and the first party of the present invention The structure of diclazuril derivative described in face is identical with optional scope, and in order to avoid repeating, the present invention is herein no longer Repeat, those skilled in the art should not be construed as limiting the invention.
Preferably, the plant mycosis is in rice sheath blight disease, gray mold of cucumber, cucumber downy mildew and powdery mildew of cucumber At least one.
Fourth aspect, the invention provides a kind of bactericide for plant epiphyte resisting disease, the active component of the bactericide For at least one of foregoing diclazuril derivative of the present invention, with the gross weight meter of the bactericide, the activity into The content divided is 0.1-100 weight %.
In the fourth aspect of the present invention, described in involved diclazuril derivative and the first aspect of the present invention The structure of diclazuril derivative is identical with optional scope, and in order to avoid repeating, the present invention will not be repeated here, this area Technical staff should not be construed as limiting the invention.
Preferably, in the bactericide, the content of active component is 1-98 weight %；More preferably 5-90 weight %.
Preferably, the formulation of the bactericide is selected from hydrating agents, pulvis, emulsion, suspending agent and granula.
The diclazuril derivative of structure shown in the previously described formula (1) and formula (2) of the present invention can be synthesized by laboratory It is made.The preparation method of classes of compounds is exemplarily provided in the example of the present invention, those skilled in the art should not be understood For limitation of the invention.
Below will the present invention will be described in detail by preparation example and test case.In following preparation example and test case, In the case of being not particularly illustrated, used various raw materials are all from commercially available.
Preparation example 1
Step 1：The preparation of formula H-2 compounds
The 7.14mmol chloro- 4- fluoronitrobenzenes of 3,5- bis- (H-1 compounds), 9.29mmol are added in 50mL round-bottomed flasks Substituted phenol is (according to R3Difference, the substituent in substituted phenol is different) and 9.29mmol potassium carbonate, add 100 DEG C are warming up to after 20mL DMF.Stop reaction after TLC monitoring raw material reactions completely, add after 50mL ether with 30mL's The 2M NaOH aqueous solution is washed 1 time with 50mL saturated common salt again after washing twice, and formula H-2 compounds are obtained after removal of solvent under reduced pressure.
Step 2：The preparation of formula H-3 compounds
3.1mmol formula H-2 compounds and 3.1mmol ammonium chloride are added in 100mL round-bottomed flask, adds 50mL Ethanol and 6mL water, be heated to backflow after add 9.3mmol reduced iron powders, TLC monitoring raw material stops after completion of the reaction instead Should, filtrate decompression is concentrated after diatomite filtering, the extraction of 50mL ethyl acetate, organic phase are added after most of solvent is removed under reduced pressure Anhydrous sodium sulfate drying is added after being washed with saturated common salt, formula H-3 compounds are obtained after removing solvent.
Step 3：The preparation of formula H-5 compounds
3.1mmol formula H-3 compounds, 10mL acetic acid and 1mL concentrated hydrochloric acids are added in 100mL round-bottomed flasks, controls temperature For 4 DEG C, the aqueous solution (including 3.4mmol natrium nitrosum and 1mL water) of natrium nitrosum is slowly added dropwise, continues after being added dropwise Half an hour is stirred, adds 0.635g NaOAc and 0.915g CH2(CONHCOOEt)2, reaction system is then moved into room temperature. 0.212g NaOAc is added after reaction half an hour, is warming up to backflow, TLC monitoring raw material reactions are finished, obtained containing formula H-4 The product of compound；Then 5mL concentrated hydrochloric acids are added thereto, continue to react, and stop reaction, decompression after TLC monitoring hydrolysis 50mL water is added after removing most of solvent, there are a large amount of solids to separate out, filters to obtain formula H-5 compounds, do not purify and directly carry out down Single step reaction.
Step 4：The preparation of formula H-6 compounds
Formula H-5 compounds and 5mL TGAs are added in 50mL round-bottomed flasks, is heated to 150 DEG C, TLC monitoring raw materials Stop reaction after reaction completely, NaHCO is added after cooling3With excessive TGA in the aqueous solution, a large amount of solids are separated out, are filtered Target compound crude product is obtained, column chromatography produces formula H-6 compounds after drying.
Specifically, the method for the invention according to preparation example 1 is by using different raw material prepare compound A1-A26.
The characterize data of each compound is as follows：
Compound A1：Fusing point is 189-192 DEG C of1H NMR(600MHz,CDCl3)δ9.37(s,1H),7.72(s,2H), 7.64 (s, 1H), 7.48 (d, J=7.9Hz, 1H), 7.13 (t, J=7.8Hz, 1H), 7.04 (t, J=7.7Hz, 1H), 6.51 (d, J=8.2Hz, 1H)13C NMR(151MHz,DMSO)δ157.32,151.75,148.02,145.37,138.76, 137.30,131.27,129.06,128.46,126.96,124.65,121.62,114.73. HRMS (ESI) theoretical value C15H8Cl3N3O3[M+H]+:383.9704. measured value：383.9702.
Compound A2：Fusing point is 170-173 DEG C of1H NMR(600MHz,DMSO)δ12.54(s,1H),7.88(s,2H), 7.75 (d, J=9.4Hz, 1H), 7.74 (s, 1H), 7.30 (t, J=7.8Hz, 1H), 7.07 (t, J=7.5Hz, 1H), 6.56 (d, J=8.2Hz, 1H)13C NMR(151MHz,CDCl3)δ155.55,152.77,146.77,136.76,136.45, 133.92,129.80,128.33,125.11,124.06,114.20,111.48.HRMS (ESI) theoretical value C15H8BrCl2N3O3 [M+H]+427.9199, measured value：427.9191.
Compound A-13：Fusing point is 174-175 DEG C of1H NMR(400MHz,CDCl3)δ9.69(s,1H),7.71(s,2H), 7.64 (s, 1H), 7.31 (d, J=5.6Hz, 1H), 7.07 (d, J=6.0Hz, 2H), 6.39 (d, J=7.2Hz, 1H), 2.54 (s,3H).13C NMR(101MHz,CDCl3)δ155.47,153.31,146.83,146.70,136.56,136.39,129.92, 127.59,126.98,125.98,125.09,123.37,112.31,15.18.HRMS (ESI) theoretical value C16H11Cl2N3O3S[M +H]+:395.9971. measured value：395.9971.
Compound A4：Fusing point is 148-150 DEG C of1H NMR(400MHz,CDCl3)δ10.38(s,1H),7.69(s,2H), 7.64 (s, 1H), 7.18 (t, J=7.5Hz, 1H), 6.91 (d, J=6.7Hz, 1H), 6.75 (s, 1H), 6.60 (d, J= 6.8Hz, 1H), 2.62 (d, J=7.2Hz, 2H), 1.21 (t, J=6.4Hz, 3H)13C NMR(101MHz,CDCl3)δ 156.37,155.96,147.02,146.92,146.33,136.39,136.30,130.04,129.34,125.11,122.38, 114.65,111.77,28.64,15.25.HRMS (ESI) theoretical value C17H13Cl2N3O3[M+H]+:378.0406. measured value： 378.0400。
Compound A-45：Fusing point is 107-108 DEG C of1H NMR(600MHz,DMSO)δ12.53(s,1H),7.85(s,2H), 7.73 (s, 1H), 7.20 (t, J=8.7Hz, 2H), 6.91 (dd, J=9.1,4.1Hz, 2H)13C NMR(151MHz,CDCl3)δ 159.18,157.58,155.67,152.43,147.05,146.88,136.57,136.49,130.07,125.26,116.31, 116.25,116.20,116.15.HRMS (ESI) theoretical value C15H8Cl2FN3O3[M+H]+:367.9999. measured value： 367.9992。
Compound A6：Fusing point is 185-186 DEG C of1H NMR(400MHz,CDCl3)δ10.12(s,1H),7.68(s,2H), 7.64 (s, 1H), 7.30 (d, J=7.9Hz, 2H), 6.78 (d, J=7.8Hz, 2H), 1.30 (s, 9H)13C NMR(101MHz, CDCl3)δ155.81,154.16,147.20,146.97,145.54,136.41,136.29,130.15,126.47,125.14, 114.38,34.17,31.42.HRMS (ESI) theoretical value C19H17Cl2N3O3[M+H]+:406.0719. measured value：406.0716.
Compound A7：Fusing point is 185-186 DEG C of1H NMR(600MHz,CDCl3)δ9.28(s,1H),7.75(s,2H), 7.65 (d, J=3.6Hz, 2H), 7.64 (s, 1H), 6.95 (d, J=8.4Hz, 2H)13C NMR(151MHz,DMSO)δ 159.56,157.30,148.01,144.57,138.98,137.34,135.32,128.50,126.93,118.87,116.29, 106.25.HRMS (ESI) theoretical value C16H8Cl2N4O3[M+H]+:375.0046. measured value 375.0042.
Compound A-28：Fusing point is 180-182 DEG C of1H NMR(600MHz,CDCl3)δ10.45(s,1H),7.70(s,2H), (7.65 s, 1H), 7.42 (s, 1H), 7.00 (d, J=8.4Hz, 1H), 6.20 (d, J=8.4Hz, 1H), 1.54 (s, 9H), 1.30 (s,9H).13C NMR(151MHz,DMSO)δ157.42,152.86,148.13,145.56,144.65,138.29,137.27, 135.86,128.92,127.05,124.60,124.29,111.80,40.40,40.27,40.13,35.23,34.55, (31.83,30.27.HRMS ESI) theoretical value C23H25Cl2N3O3[M+H]+:462.1346. measured value 462.1356.
Compound A9：Fusing point is 185-187 DEG C of1H NMR(600MHz,DMSO)δ12.54(s,1H),7.87(s,2H), 7.74 (s, 1H), 7.56 (d, J=2.1Hz, 1H), 7.26 (dd, J=8.7,2.1Hz, 1H), 6.49 (d, J=8.7Hz, 1H), 1.26(s,9H).13C NMR(101MHz,CDCl3)δ155.81,154.16,147.20,146.97,145.54,136.41, 136.29,130.15,126.47,125.14,114.38,34.17,31.42.HRMS (ESI) theoretical value C19H16Cl3N3O3[M+ H]+:439.0330. measured value 439.0341.
Compound A10：Fusing point is 177-178 DEG C of1H NMR(600MHz,DMSO)δ12.52(s,1H),7.86(s,2H), 7.74 (s, 1H), 7.69 (d, J=2.4Hz, 1H), 7.31 (dd, J=9.0,1.8Hz, 1H), 6.45 (d, J=9.0Hz, 1H), 1.26(s,9H).13C NMR(151MHz,CDCl3)δ155.46,150.51,147.36,147.06,146.72,136.67, 136.43,130.98,129.90,125.23,125.08,113.65,110.92,34.33,3 1.29.HRMS (ESI) theoretical value C19H16BrCl2N3O3[M+Na]+:505.9644. measured value 505.9648.
Compound A11：Fusing point is 172-173 DEG C of1H NMR(600MHz,DMSO)δ12.50(s,1H),7.83(s,1H), 7.72 (s, 1H), 7.33 (s, 1H), 7.09 (d, J=10.2Hz, 1H), 6.23 (d, J=9.0Hz, 1H), 2.39 (s, 3H), 1.25(s,9H).13C NMR(151MHz,DMSO)δ157.46,152.52,148.13,146.44,145.30,138.21, 137.21,128.86,128.75,126.84,125.40,124.06,111.84,34.28,31.69,16.58.HRMS(ESI) Theoretical value C20H19Cl2N3O3[M+H]+:420.0876. measured value 420.0879.
Compound A12：Fusing point is 231-233 DEG C of1H NMR(600MHz,DMSO)δ12.53(s,1H),7.83(s,2H), 7.73(s,1H),6.74(s,1H),6.45(s,2H),2.23(s,6H).13C NMR(151MHz,DMSO)δ156.88, 156.14,147.61,145.27,139.46,137.84,136.80,128.42,126.39,124.54,112.07, 20.90.HRMS (ESI) theoretical value C17H13Cl2N3O3[M+Na]+:400.0226. measured value 400.0223.
Compound A13：Fusing point is 171-173 DEG C of1H NMR(600MHz,DMSO)δ12.50(s,1H),7.75(s,2H), 7.71 (s, 1H), 7.58 (d, J=8.2Hz, 2H), 7.28 (t, J=8.1Hz, 1H)13C NMR(151MHz,DMSO)δ 157.32,148.02,147.60,146.95,137.18,137.04,130.24,126.90,125.97,125.25.HRMS (ESI) theoretical value C15H7Cl4N3O3[M+H]+:417.9314. measured value 417.9311.
Compound A14：Fusing point is 248-250 DEG C of1H NMR(600MHz,DMSO)δ12.46(s,1H),7.72(s,2H), 7.69 (s, 1H), 7.56 (d, J=8.4Hz, 2H), 7.24 (d, J=8.4Hz, 1H)13C NMR(151MHz,DMSO)δ 157.26,152.26,147.99,144.73,139.03,137.36,133.03,132.49,128.20,126.90,124.77, 120.77,114.74.HRMS (ESI) theoretical value C15H7Cl4N3O3[M+H]+:417.9314. measured value 417.9319.
Compound A15：Fusing point is 147-149 DEG C of1H NMR(600MHz,DMSO)δ12.50(s,1H),7.83(s,2H), 7.76(s,2H),7.71(s,1H).13C NMR(151MHz,CDCl3)δ155.66,147.65,147.08,146.76, 136.30,135.28,129.73,128.96,127.27,126.42,125.07.HRMS (ESI) theoretical value C15H6Cl5N3O3[M+ H]+:451.8925. measured value 451.8922.
Compound A16：Fusing point is 168-170 DEG C of13C NMR(151MHz,CDCl3)δ155.84,154.50,147.12, 146.96,138.24,136.40,136.28,130.94,130.44,130.15,125.14,116.18,111.75,19.98, 18.90.HRMS (ESI) theoretical value C17H13Cl2N3O3[M+Na]+:400.0226. measured value 400.0227.
Compound A17：Fusing point is 194-196 DEG C of1H NMR(600MHz,DMSO)δ12.54(s,1H),7.88(s,2H), 7.74 (s, 1H), 7.22 (d, J=7.2Hz, 1H), 7.14 (d, J=8.4Hz, 1H), 6.56 (t, J=7.8Hz, 1H)13C NMR (151MHz,DMSO)δ157.29,152.02,150.32,148.00,145.38,145.00,141.17,139.52,138.95, 137.33,128.36,126.90,125.04,112.23,111.44.HRMS (ESI) theoretical value C15H7Cl2F2N3O3[M+H]+: 385.9905. measured value 385.9909.
Compound A18：Fusing point is 161-163 DEG C of1H NMR(600MHz,DMSO)δ12.53(s,1H),7.86(s,2H), 7.74 (s, 1H), 7.38 (t, J=9.0Hz, 1H), 7.33 (dd, J=5.4,3.1Hz, 1H), 6.92 (dd, J=8.0,4.8Hz, 1H).13C NMR(151MHz,CDCl3)δ155.19,151.89,146.74,146.53,136.78,136.42,130.92, 129.85,127.62,125.12,123.72,122.75,114.40.HRMS (ESI) theoretical value C15H7BrCl2FN3O3[M+H]+: 444.9032. measured value：444.9035.
Compound A19：Fusing point is 200-202 DEG C of1H NMR(600MHz,CDCl3)δ9.09(s,1H),7.72(s,2H), 7.64 (s, 1H), 7.21-7.15 (m, 1H), 6.70 (td, J=8.4,2.4Hz, 1H), 6.11 (dd, J=9.6,2.4Hz, 1H), 2.41(s,3H).13C NMR(151MHz,CDCl3)δ162.25,160.63,155.59,154.93,154.87,146.89, 146.77,136.63,136.42,131.66,131.60,129.80,125.14,122.27,109.17,109.04,100.82, 100.65,15.53.HRMS (ESI) theoretical value C16H10Cl2FN3O3[M+H]+:382.0156. measured value 382.0148.
Compound A20：Fusing point is 177-179 DEG C of1H NMR(600MHz,CDCl3)δ9.00(s,1H),7.71(s,2H), 7.63 (s, 1H), 7.29 (s, 1H), 6.91 (d, J=8.4Hz, 1H), 6.39 (d, J=8.4Hz, 1H), 2.30 (s, 3H)13C NMR(151MHz,CDCl3)δ155.15,149.71,146.93,146.48,136.60,136.32,133.53,131.22, 129.80,127.98,125.04,122.18,114.09,20.35.HRMS (ESI) theoretical value C16H10Cl3N3O3[M+H]+: 397.9861. measured value 397.9863.
Compound A21：Fusing point is 203-205 DEG C of1H NMR(600MHz,DMSO)δ12.52(s,1H),7.84(s,2H), 7.73(s,1H),6.15(s,2H),3.69(s,6H),3.61(s,3H).13C NMR(151MHz,DMSO)δ157.33, 154.10,152.99,148.04,145.45,138.36,137.25,133.59,128.86,126.79,92.97,60.56, 56.45.HRMS (ESI) theoretical value C18H15Cl2N3O6[M+H]+:440.0411. measured value 440.0408.
Compound A22：Fusing point is 205-207 DEG C of1H NMR(600MHz,DMSO)δ12.50(s,1H),7.84(s,2H), 7.71 (s, 1H), 7.19 (d, J=7.2Hz, 1H), 7.10 (d, J=8.4Hz, 1H), 6.51 (t, J=7.8Hz, 1H)13C NMR (151MHz,DMSO)δ156.87,155.22,147.58,144.42,138.46,136.90,132.32,131.69,128.10, 126.52,125.31,117.19,115.05.HRMS (ESI) theoretical value C15H7Cl4N3O3[M+H]+:417.9314. measured value 417.9310。
Compound A23：Fusing point is 194-195 DEG C of1H NMR(600MHz,DMSO)δ12.51(s,1H),7.76(s,1H), 7.57 (s, 1H), 7.35 (d, J=7.8Hz, 1H), 7.17 (dd, J=7.2,4.8Hz, 1H), 7.07 (dd, J=8.4,4.2Hz, 1H), 7.04 (d, J=7.8Hz, 1H), 2.53 (s, 3H), 2.15 (s, 3H)13C NMR(151MHz,DMSO)δ160.11, 152.83,148.45,148.32,146.02,132.14,129.18,126.56,125.91,124.87,122.34,122.06, 119.76,119.13,118.79,113.96,15.15,14.33.HRMS (ESI) theoretical value C18H13F3ClN3O3S[M+H]+: 444.0318. measured value 444.0317.
Compound A24：Fusing point is 211-213 DEG C of1H NMR(600MHz,DMSO)δ12.51(s,1H),7.50(s,1H), 7.45 (d, J=7.2Hz, 1H), 7.29 (dd, J=8.4,4.8Hz, 1H), 7.11 (dd, J=7.8,4.2Hz, 1H), 7.08 (d, J=7.2Hz, 1H), 2.21 (s, 6H)13C NMR(151MHz,DMSO)δ157.16,151.95,148.34,142.12, 138.98,135.52,133.14,130.95,126.51,125.83,124.01,123.22,120.53,14.21.HRMS (ESI) theoretical value C17H12Cl3N3O3[M+H]+:411.9944. measured value 411.9946.
Compound A25：Fusing point is 198-199 DEG C of1H NMR (600MHz, DMSO) δ 12.48 (s, 1H), 7.56 (d, J= 7.2Hz, 1H), 7.51 (s, 1H), 7.35 (dd, J=7.2,4.8Hz, 1H), 7.06 (dd, J=8.4,4.2Hz, 1H), 7.03 (d, J=7.8Hz, 1H), 6.96 (s, 1H) 2.88-2.87 (m, 1H), 2.25 (s, 3H), 1.20 (d, J=7.2Hz, 6H)13C NMR(151MHz,DMSO)δ157.12,154.09,147.58,148.32,147.13,139.30,138.92,134.81, 132.56,127.42,124.02,122.83,114.75,112.05,111.84,28.36,23.36,14.28.HRMS(ESI) Theoretical value C19H17BrClN3O3[M+H]+:450.0142. measured value 450.0143.
Compound A26：Fusing point is 224-245 DEG C of1H NMR (600MHz, DMSO) δ 12.46 (s, 1H), 8.22 (d, J= 7.8Hz, 1H), 7.95 (s, 1H), 7.81 (d, J=7.2Hz, 1H), 7.80 (dd, J=9.0,4.8Hz, 1H), 7.78 (dd, J= 9.0,4.8Hz, 1H), 7.65 (s, 1H), 7.50 (s, 1H), 7.20 (s, 1H)13C NMR(151MHz,DMSO)δ157.12, 149.74,148.31,147.56,138.98,138.69,134.55,132.28,126.64,126.07,124.15,122.73, 121.76,119.13,117.45.HRMS (ESI) theoretical value C15H9ClN4O5[M+H]+:361.0261. measured value 361.0262.
Test case 1
Butanedioic acid cytochrome c oxidoreductase (Succinate-cytochrome c reductase, SCR) is compound Thing II and Complex II I mixture.The test of SQR activity is to use butanedioic acid and dichlorophenolindophenol in SCR (dichlorophenolindophenol, DCIP) determines as substrate, and the measure of Complex II I activity is to use decylubiquinol(DBH2) and cytochrome c (cytochrome c) be used as substrate, the test of SCR enzymatic activitys is to use amber Acid and cytochrome c are as substrate.According to compound enzyme inhibition activity method of testing, compound A1-A26 activity is tested, Active testing result is as shown in table 1.
Also, the active testing result of existing goods S- diclazurils is additionally provided in table 1.
Table 1
Numbering IC50(μM) Numbering IC50(μM)
A1 31.46±1.21 A15 16.23±1.09
A2 4.20±0.15 A16 22.96±1.14
A3 34.23±1.08 A17 0.61±0.12
A4 26.74±1.28 A18 19.06±1.13
A5 5.07±1.25 A19 6.30±0.11
A6 2.16±0.15 A20 23.77±1.03
A7 0.0116±0.00114 A21 1.36±0.11
A8 0.40±0.01 A22 1.51±0.12
A9 1.30±0.14 A23 1.25±0.18
A10 1.39±0.11 A24 2.18±0.19
A11 1.25±0.16 A25 5.23±1.05
A12 15.14±1.10 A26 4.26±0.14
A13 3.89±1.21 S- diclazurils 36.22±1.50
A14 0.18±0.01
As can be seen that the compound of the present invention is all shown to Pigs Hearts source SCR from enzyme inhibition activity test result Good inhibitory activity, and the effect of most compounds is better than the comparison medicament diclazuril of commercialization.
Test case 2
It is horizontal that live body is carried out to the partial target compound in synthesized compound A1-A26 using greenhouse pot culture experiment Bactericidal activity measure.Test result is as shown in table 2.
Table 2
From the results shown in Table 2, compound of the invention is white to rice sheath blight disease, cucumber under 200mg/L concentration Powder disease and gray mold of cucumber do not show significant activity all, but the above-claimed cpd of the present invention is in 200mg/L concentration Under preferable preventive effect is shown to cucumber downy mildew.
Preparation example 2
Step 1：The preparation of formula G-2 compounds
10mmol formula G-1 compounds are added in 100mL round-bottomed flasks (according to R3The difference of substituent, selection are different The raw material of species), the dichloromethane and 20mmol pyridine that 50mL is dried, the two of methylchloroformate is slowly added dropwise under condition of ice bath Chloromethanes solution (10mmol/20mL), react 1h after TLC monitoring raw material reaction finish, be neutralized to reaction system with 2M hydrochloric acid To neutrality, anhydrous sodium sulfate drying after saturated common salt water washing, removal of solvent under reduced pressure obtains formula G-2 compounds, straight without purification Row is tapped into react in next step.
Step 2：The preparation of formula G-3 compounds
5mmol formula G-2 compounds are added in 50mL round-bottomed flasks, the DMF that 30mL is dried, are added under ice bath 7.5mmol 60 weight % NaH, 5mmol formula G-4 compounds are dissolved in the DMF of 10mL dryings after reaction half an hour, delayed Slowly reaction system is added dropwise to, 120 DEG C is warming up to after rear normal-temperature reaction half an hour is added dropwise, TLC monitorings raw material after reacting 6 hours Reaction is complete, pours into 150mL frozen water system after stopping reaction, separates out a large amount of solids, will produce formula G-3ization after its column chromatography Compound.
Specifically, method prepare compound C1-C12 of the present invention by using corresponding raw material according to preparation example 2.
The characterize data of each compound is as follows：
Compound C1：Fusing point is 169-171 DEG C；1H NMR(600MHz,DMSO)δ12.73(s,1H),7.78(s,2H), 7.44 (s, 1H), 7.09 (d, J=7.8Hz, 1H), 6.45 (s, 1H), 6.40 (d, J=8.4Hz, 1H), 2.27 (s, 3H)13C NMR(151MHz,DMSO)δ161.78,151.74,150.55,145.30,139.87,139.64,139.38,134.17, 132.50,132.26,130.76,128.04,124.42,122.04,120.48,120.22,118.41,116.59,114.00, 100.62,21.21.HRMS (ESI) theoretical value C18H10Cl3F3N2O3[M+H]+:464.9782. measured value 464.9788.
Compound C2：Fusing point is 178-181 DEG C；1H NMR(600MHz,DMSO)δ12.76(s,1H),7.84(s,2H), 7.71 (d, J=8.4Hz, 1H), 7.28 (d, J=8.4Hz, 1H), 6.52 (d, J=1.8Hz, 1H), 6.46 (s, 1H)13C NMR (151MHz,DMSO)δ161.78,151.77,150.59,145.32,139.90,139.66,139.41,134.21,132.53, 132.30,130.79,128.07,124.45,122.08,120.51,120.26,118.43,116.61,114.03, 100.68.HRMS (ESI) theoretical value C17H7Cl4F3N2O3[M+H]+:484.9236. measured value 484.9226.
Compound C3：Fusing point is 192-193 DEG C；1H NMR(600MHz,DMSO)δ12.73(s,1H),7.81(s,2H), 7.62 (d, J=7.8Hz, 1H), 7.31 (t, J=7.8Hz, 1H), 7.15 (t, J=7.8Hz, 1H), 6.53 (d, J=8.4Hz, 1H),6.46(s,1H).13C NMR(151MHz,DMSO)δ161.77,151.27,150.59,145.86,139.82,139.58, 133.81,130.94,130.60,128.70,128.27,124.27,121.26,120.24,118.42,114.14, 100.68.HRMS (ESI) theoretical value C17H8Cl3F3N2O3[M+H]+:450.9625. measured value 450.9632.
Compound C4：Fusing point is 184-187 DEG C；1H NMR(600MHz,DMSO)δ12.74(s,1H),7.82(s,2H), 7.26-7.21 (m, 1H), 7.20-7.13 (m, 1H), 6.48 (t, J=7.8Hz, 1H), 6.46 (s, 1H)13C NMR(151MHz, DMSO)δ161.79,151.62,150.62,150.05,149.99,145.56,144.92,140.71,139.91,139.67, 139.17,134.08,130.66,128.19,124.76,120.26,118.44,111.92,111.81,110.93,109.58, 100.68.HRMS (ESI) theoretical value C17H7Cl2F5N2O3[M+H]+:452.9827. measured value 452.9820.
Compound C5：Fusing point is 159-161 DEG C；1H NMR(600MHz,DMSO)δ12.71(s,1H),7.76(s,2H), 7.25 (t, J=7.8Hz, 1H), 6.93 (d, J=7.8Hz, 1H), 6.72 (s, 1H), 6.57 (d, J=7.8Hz, 1H), 6.45 (s,1H),2.30(s,3H).13C NMR(151MHz,DMSO)δ161.81,156.07,150.62,146.11,139.93, 133.32,130.42,129.82,128.67,123.76,115.19,111.34,100.69 21.01.HRMS (ESI) theoretical value C18H11Cl2F3N2O3[M+H]+:431.0172. measured value 431.0179.
Compound C6：Fusing point is 188-191 DEG C；1H NMR(600MHz,DMSO)δ12.72(s,1H),7.77(s,2H), 7.40 (d, J=2.4Hz, 1H), 7.16 (dd, J=8.4,2.4Hz, 1H), 6.45 (s, 1H), 6.13 (d, J=8.5Hz, 1H), 1.54(s,9H),1.30(s,9H).13C NMR(151MHz,DMSO)δ160.61,152.32,151.11,145.99,144.29, 135.40,133.54,130.14,128.80,124.15,123.95,111.15,103.27,31.36,29.80.HRMS(ESI) Theoretical value C26H27Cl2F3N2O3[M+H]+:529.1267. measured value 529.1263.
Compound C7：Fusing point is 163-164 DEG C；13C NMR(151MHz,DMSO)δ161.76,150.58,147.31, 147.22,139.76,139.51,131.77,130.47,129.77,126.57,125.69,124.92,120.24,118.42, 100.63.HRMS (ESI) theoretical value C17H7Cl4F3N2O3[M+H]+:484.9236. measured value 484.9233.
Compound C8：Fusing point is 187-188 DEG C；1H NMR(600MHz,DMSO)δ12.61(s,1H),7.71(s,2H), 7.55 (d, J=2.4Hz, 2H), 7.25 (d, J=2.4Hz, 2H), 5.70 (s, 1H), 4.05 (s, 2H), 1.33 (s, 9H)13C NMR(151MHz,DMSO)δ165.61,153.92,153.71,149.83,144.42,142.34,128.62,127.44, 124.79,119.85,115.36,103.45,40.93,34.23,31.37.HRMS (ESI) theoretical value C21H19Cl3N2O3[M+H ]+:453.0461. measured value 453.0465.
Compound C9：Fusing point is 192-194 DEG C；1H NMR (600MHz, DMSO) δ 12.47 (s, 1H), 7.85 (d, J= 2.4Hz, 2H), 7.74 (s, 2H), 7.16 (d, J=2.4Hz, 2H), 2.44 (q, J=3.0Hz, 2H), 1.33 (t, J=2.4Hz, 3H).13C NMR(151MHz,DMSO)δ161.32,159.92,153.03,142.36,131.95,128.64,127.46, 119.87,118.62,118.21,108.23,105.74,24.23,21.37.HRMS (ESI) theoretical value C19H12Cl3N3O3[M+ H]+:435.9944. measured value 435.9945.
Compound C10：Fusing point is 178-180 DEG C；1H NMR(600MHz,DMSO)δ12.50(s,1H),7.66(s,1H), 7.33(s,2H),6.22(s,1H),2.24(s,3H).13C NMR(151MHz,DMSO)δ165.32,153.02,144.88, 142.25,133.29,131.45,130.22,130.02,128.23,127.06,125.13,124.47,119.71,115.23, 114.56,28.47.HRMS (ESI) theoretical value C18H8Cl5N3O3[M+H]+:489.9008. measured value 489.9006.
Compound C11：Fusing point is 203-204 DEG C；1H NMR(600MHz,DMSO)δ12.62(s,1H),7.83(s,1H), 7.45 (s, 1H), 7.38 (d, J=2.4Hz, 1H), 7.22 (d, J=3.0Hz, 1H), 7.03 (d, J=2.4Hz, 1H), 6.86 (d, J=2.4Hz, 1H), 6.77 (s, 1H), 1.32 (s, 9H)13C NMR(151MHz,DMSO)δ165.04,161.59, 153.06,148.87,147.56,144.52,127.89,127.21,126.04,125.63,124.56,123.18,122.84, 121.74,119.15,99.45,33.79,31.32.HRMS (ESI) theoretical value C20H17Cl2N3O5[M+H]+:450.0545. measure Value 450.0544.
Compound C12：Fusing point is 182-184 DEG C；1H NMR(600MHz,DMSO)δ12.48(s,1H),7.78(s,1H), 7.41 (s, 1H), 7.35 (d, J=2.4Hz, 1H), 7.25 (d, J=2.4Hz, 1H), 6.93 (s, 1H), 5.43 (s, 1H), 2.31 (s,3H),2.12(s,3H),2.08(s,3H),1.28(s,9H).13C NMR(151MHz,DMSO)δ166.04,151.49, 151.36,149.84,147.46,146.92,133.47,130.12,127.31,126.64,123.63,121.76,121.68, 117.94,117.05,102.14,34.52,19.21,18.65,17.85,17.29.HRMS (ESI) theoretical value C20H17Cl2N3O5 [M+H]+:450.0545. measured value 450.0544.
Test case 3
Using the enzyme inhibition activity with the identical method test compound C1-C12 of test case 1, in its Activity Results such as table 3 It is shown.
Table 3
From the results shown in Table 3, compound C1-C12 of the invention is shown well to the SCR in Pigs Hearts source Inhibitory activity, and the positive effect of compound be better than commercialization comparison medicament diclazuril.
Preparation example 3
Step 1：The preparation of formula K-2 compounds
The 3.1mmol chloro- PABAs of 2- (formula K-1 compounds), 10mL vinegar are added in 100mL round-bottomed flasks The aqueous solution (the natrium nitrosum containing 3.4mmol of natrium nitrosum is slowly added dropwise at 4 DEG C in the concentrated hydrochloric acid of acid and 1mL, control temperature With 1mL water), continue to stir half an hour after being added dropwise, add 0.635g NaOAc and 0.915g CH2 (CONHCOOEt)2, then reaction system is moved to and adds 0.212g NaOAc after room temperature reaction half an hour and is warming up to backflow, TLC monitoring raw materials add 5mL concentrated hydrochloric acids after completion of the reaction, continue to react, and stop reaction after TLC monitoring hydrolysis, decompression removes Go after most of solvent to add 50mL water, there are a large amount of solids to separate out, filter to obtain formula K-2 compounds, do not purify and directly carry out down Single step reaction.
Step 2：The preparation of formula K-4 compounds
Formula K-2 compounds and 5mL TGAs are added in 50mL round-bottomed flasks, is heated to 150 DEG C, TLC monitoring raw materials Stop reaction after completion of the reaction, obtain the product containing formula K-3 compounds, add NaHCO after cooling3It is in the aqueous solution and excessive TGA, separate out a large amount of solids, filter to obtain target compound crude product, formula K-4 compounds are produced after drying.
Step 3：The preparation of formula K-5 compounds
1.87mmol formula K-4 compounds and 10mL thionyl chlorides is added in 50mL round-bottomed flasks, is heated to flowing back, instead Answer to be evaporated under reduced pressure after 3h and remove excess thionyl chloride, the dichloromethane for adding 30mL dryings is dissolved, be slowly added dropwise to The phenol of 2.80mmol substitutions is (according to R3The difference of group, substituted starting phenol are different) and 5.7mmol triethylamine two In chloromethanes solution, reacted 2 hours after being added dropwise, TLC monitoring raw materials stop reacting after completion of the reaction, after saturated common salt washing Anhydrous sodium sulfate drying, column chromatography obtains formula K-5 compounds after removal of solvent under reduced pressure.
Specifically, method prepare compound B1-B16 of the present invention by using corresponding raw material according to preparation example 3.
The characterize data of each compound is as follows：
Compound B-11：Fusing point is 159-161 DEG C；1H NMR (600MHz, DMSO) δ 12.51 (s, 1H), 8.25 (d, J= 8.5Hz, 1H), 7.88 (d, J=1.4Hz, 1H), 7.80-7.69 (m, 2H), 7.57 (d, J=8.8Hz, 2H), 7.40 (d, J= 8.8Hz,2H).13C NMR(151MHz,DMSO)δ162.53,156.82,149.03,147.56,143.86,137.25, 132.86,132.49,130.50,129.61,126.81,126.69,123.84,123.43. HRMS (ESI) theoretical value C16H9Cl2N3O4[M+H]+:378.0043. measured value 378.0048.
Compound B2：Fusing point is 179-180 DEG C；1H NMR (600MHz, DMSO) δ 12.50 (s, 1H), 8.31 (d, J= 8.4Hz, 1H), 7.91 (s, 1H), 7.79 (d, J=7.8Hz, 1H), 7.77 (s, 1H), 7.67 (d, J=7.8Hz, 1H), 7.54 (d, J=8.4Hz, 1H), 7.49 (t, J=7.2Hz, 1H), 7.40 (t, J=7.8Hz, 1H)13C NMR(151MHz,DMSO)δ 161.63,156.81,147.56,146.27,144.14,137.31,133.15,132.57,130.28,128.71,128.13, 126.99,125.86,124.35,123.57.HRMS (ESI) theoretical value C16H9Cl2N3O4[M+H]+:378.0043. measured value 378.0040。
Compound B3：Fusing point is 176-178 DEG C；1H NMR (600MHz, DMSO) δ 12.51 (s, 1H), 8.19 (d, J= 8.4Hz, 1H), 7.87 (d, J=1.Hz, 1H), 7.76 (s, 1H), 7.74 (dd, J=8.4,1.8Hz, 1H), 6.97 (s, 1H), 6.94(s,2H),2.32(s,6H).13C NMR(151MHz,DMSO)δ162.96,156.82,150.19,147.56,143.65, 139.10,137.20,132.48,132.10,127.71,127.42,126.78,123.52,119.20,20.77.HRMS (ESI) theoretical value C18H14ClN3O4[M+H]+:372.0746. measured value 372.0759.
Compound B4：Fusing point is 180-182 DEG C；1H NMR (600MHz, dmso) δ 12.51 (s, 1H), 8.27 (d, J= 8.4Hz, 1H), 7.89 (d, J=1.8Hz, 1H), 7.79-7.74 (m, 2H), 7.27 (d, J=7.8Hz, 1H), 7.13 (d, J= 7.8Hz, 2H), 2.91 (m, 1H), 2.17 (s, 3H), 1.21 (d, J=6.6Hz, 6H)13C NMR(151MHz,DMSO)δ 162.87,156.57,150.23,147.59,143.73,139.31,137.45,132.44,132.30,127.67,127.75, 126.91,123.58,117.35,35.31,30.12,20.19.HRMS (ESI) theoretical value C20H18ClN3O4[M+H]+: 400.1059. measured value 400.1054.
Compound B5：Fusing point is 193-196 DEG C；1H NMR (600MHz, dmso) δ 12.52 (s, 1H), 8.29 (d, J= 8.4Hz 1H), 7.90 (d, J=1.8Hz, 1H), 7.79 (dd, J=8.4,1.8Hz, 1H), 7.77 (s, 1H), 7.44 (d, J= 7.8Hz 1H), 7.37 (t, J=7.2Hz, 1H), 7.31 (m, 2H), 2.46 (s, 3H)13C NMR(151MHz,DMSO)δ 161.94,156.82,147.57,146.97,143.96,137.27,133.04,132.33,131.43,127.26,127.00, 126.75,126.41,125.90,123.58,122.59,14.12.HRMS (ESI) theoretical value C17H12ClN3O4S[M+H]+: 390.0310. measured value 390.0298.
Compound B-26：Fusing point is 182-184 DEG C；1H NMR (600MHz, dmso) δ 12.51 (s, 1H), 8.21 (d, J= 8.4Hz 1H), 7.87 (s, 1H), 7.75 (d, J=8.4Hz, 2H), 7.29 (d, J=7.2Hz, 2H), 7.21 (d, J=7.8Hz, 2H),2.34(s,3H).13C NMR(151MHz,DMSO)δ163.45,161.57,159.12,156.45,150.22,149.42, 147.81,144.11,137.85,132.99,127.23,126.98,126.33,123.88,113.75,110.67, 17.49.HRMS (ESI) theoretical value C17H12ClN3O4[M+H]+:358.0589. measured value 358.0593.
Compound B7：Fusing point is 212-214 DEG C；1H NMR (600MHz, dmso) δ 12.51 (s, 1H), 8.29 (d, J= 8.4Hz, 1H), 7.89 (d, J=2.4Hz, 1H), 7.77 (t, J=7.2Hz, 2H), 7.45-7.39 (m, 1H), 7.31 (dd, J= 9.0,2.4Hz 1H), 7.14 (td, J=9.8,7.2Hz, 1H), 2.19 (s, 3H)13C NMR(151MHz,DMSO)δ162.11, 161.27,159.65,156.83,149.27,149.19,147.57,143.92,137.26,132.82,132.42,132.01, 126.92,126.61,126.15,123.58,113.37,113.23,110.07,109.91 15.28.HRMS (ESI) theoretical value C17H11ClFN3O4[M+H]+:376.0495. measured value 376.0490.
Compound B8：Fusing point is 223-224 DEG C；1H NMR (600MHz, dmso) δ 12.51 (s, 1H), 8.33 (d, J= 9.0Hz, 1H), 7.93 (d, J=1.8Hz, 1H), 7.84 (d, J=2.4Hz, 1H), 7.80 (dd, J=8.4,1.8Hz, 1H), 7.76 (s, 1H), 7.75 (d, J=9.0Hz, 1H), 7.53 (dd, J=8.4,2.4Hz, 1H), 2.18 (s, 6H)13C NMR (151MHz,DMSO)δ163.06,156.83,148.18,147.56,143.63,137.84,137.20,134.28,132.45, 132.12,130.29,127.46,126.81,123.56,122.42,118.75,18.84.H RMS (ESI) theoretical value C18H14ClN3O4[M+H]+:372.0746. measured value 372.0746.
Compound B9：Fusing point is 192-194 DEG C；1H NMR (600MHz, dmso) δ 12.52 (s, 1H), 8.32 (d, J= 9.0Hz, 1H), 7.92 (d, J=1.8Hz, 1H), 7.82 (d, J=2.4Hz, 1H), 7.80 (dd, J=8.4,1.8Hz, 1H), 7.78 (s, 1H), 7.72 (d, J=9.0Hz, 1H), 7.51 (dd, J=8.4,2.4Hz, 1H)13C NMR(151MHz,DMSO)δ 161.21,156.79,147.55,146.84,144.29,137.34,133.37,132.77,132.34,131.39,128.12, 126.99,125.40,125.06,124.67,123.52.HRMS (ESI) theoretical value C16H8Cl3N3O4[M+H]+:411.9653. Measured value 411.9652.
Compound B-11 0：Fusing point is 205-207 DEG C；1H NMR (600MHz, dmso) δ 12.52 (s, 1H), 8.32 (d, J= 8.4Hz, 1H), 7.91 (d, J=2.4Hz, 1H), 7.79 (dd, J=8.4,24Hz, 1H), 7.77 (s, 1H), 7.72 (dd, J= 8.4,3.0Hz, 1H), 7.63 (dd, J=9.0,5.4Hz, 1H), 7.40 (td, J=8.4,3.0Hz, 1H)13C NMR (151MHz,DMSO)δ163.11,157.71,148.59,146.84,143.45,138.74,135.58,134.34,132.53, 131.42,129.41,128.21,126.21,125.76,125.67,124.10.HRMS (ESI) theoretical value C16H8Cl2FN3O4[M +H]+:395.9949. measured value 395.9943.
Compound B-11 1：Fusing point is 209-210 DEG C；1H NMR (600MHz, dmso) δ 12.51 (s, 1H), 8.42 (d, J= 8.4Hz, 1H), 7.87 (s, 1H), 7.53 (d, J=8.4,1H), 7.48 (d, J=8.4Hz, 2H), 7.46 (d, J=8.4,2H), 2.07(s,3H).13C NMR(151MHz,DMSO)δ165.21,160.14,148.39,147.53,146.03,144.38, 135.21,131.98,131.15,130.36,128.34,127.45,121.92,119.61 18.74.HRMS (ESI) theoretical value C17H11Cl2N3O4[M+H]+:392.0127. measured value 392.0125.
Compound B-11 2：Fusing point is 195-197 DEG C；1H NMR (600MHz, dmso) δ 12.54 (s, 1H), 8.42 (d, J= 8.4Hz, 1H), 7.87 (s, 1H), 7.53 (d, J=8.4,1H), 7.24 (s, 1H)), 7.23 (s, 2H), 2.27 (s, 6H), 1.69-1.68 (m, 1H), 1.21 (d, J=8.4Hz, 6H)13C NMR(151MHz,DMSO)δ165.21,160.42,158.35, 148.39,146.53,144.39,140.68,135.21,131.98,127.74,127.43,121.96,119.61,119.36, (29.25,21.63,18.24.HRMS ESI) theoretical value C21H20ClN3O4[M+H]+:314.1142. measured value 314.1145.
Compound B-11 3：Fusing point is 211-212 DEG C；1H NMR (600MHz, dmso) δ 12.52 (s, 1H), 8.45 (d, J= 8.4Hz, 1H), 7.86 (s, 1H), 7.56 (d, J=8.4,1H), 7.43 (d, J=8.4,1H), 7.23 (dd, J=8.4, 2.4Hz, 1H), 7.22 (dd, J=8.4,2.4Hz, 1H), 7.13 (d, J=8.4,1H), 2.46 (s, 3H)13C NMR (151MHz,DMSO)δ165.31,160.12,148.35,146.09,144.53,135.91,135.28,131.95,127.43, 127.21,126.47,125.7,125.5,121.95,121.86,119.71,119.66,16 .24.HRMS (ESI) theoretical value C21H20ClN3O4[M+H]+:314.1142. measured value 314.1145.
Compound B-11 4：Fusing point is 198-200 DEG C；1H NMR(600MHz,dmso)δ12.46(s,1H),7.66(s,1H), 7.56 (d, J=8.4,1H), 7.50 (s, 1H), 7.40 (dd, J=8.4,3.0Hz, 1H), 7.31 (d, J=8.4,1H), 7.29 (dd, J=8.4,3.0Hz, 1H), 2.21 (s, 3H), 2.12 (s, 3H)13C NMR(151MHz,DMSO)δ165.29,157.14, 148.39,147.53,146.39,138.93,135.21,132.28,131.65,131.08,129.14,127.33,127.26, 127.21,126.95,124.17,21.63,18.24.HRMS (ESI) theoretical value C18H13Cl2N3O4[M+H]+:406.0238. survey Obtain value 406.0240.
Compound B-11 5：Fusing point is 178-179 DEG C；1H NMR(600MHz,dmso)δ12.43(s,1H),7.76(s,1H), 7.66 (d, J=8.4,1H), 7.51 (s, 1H), 7.46 (dd, J=8.4,3.0Hz, 1H), 7.26 (d, J=8.4,1H), 7.24 (dd, J=8.4,3.0Hz, 1H), 2.87-2.86 (m, 1H), 1.2 (d, J=8.4,6H)13C NMR(151MHz,DMSO)δ 165.27,157.14,148.89,148.33,143.39,139.53,138.91,135.28,133.25,131.28,128.14, 127.73,127.06,126.21,123.81,116.43,28.09,23.63,18.74.HRM S (ESI) is theoretical C20H17BrClN3O4[M+H]+:478.0091. measured value 478.0079.
Compound B-11 6：Fusing point is 194-196 DEG C；1H NMR (600MHz, dmso) δ 12.47 (s, 1H), 8.33 (d, J= 8.4,1H), 8.02 (s, 2H), 7.96 (dd, J=8.4,3.0Hz, 1H), 7.91 (dd, J=8.4,3.0Hz, 1H), 7.63 (d, J =8.4,1H), 7.51 (s, 1H)13C NMR(151MHz,DMSO)δ165.23,157.54,148.39,145.33,140.39, 138.97,136.91,136.68,135.25,128.74,127.73,126.21,124.81 120.43.HRMS (ESI) is theoretical C16H8Cl2N4O6[M+H]+:422.9821. measured value 422.9826.
Test case 4
Using the enzyme inhibition activity with the identical method test compound B1-B16 of test case 1, in its Activity Results such as table 4 It is shown.
Table 4
Numbering IC50(μM)
B1 >100
B2 >100
B3 >100
B4 4.13±1.44
B5 10.55±1.13
B6 >100
B7 >100
B8 18.01±1.27
B9 >100
B10 >100
B11 4.36±1.41
B12 5.26±1.12
B13 1.25±1.36
B14 5.89±1.10
B15 1.29±1.41
B16 1.87±1.25
As can be seen that the majority of compounds of the present invention is to Pigs Hearts source SCR all tables from enzyme inhibition activity test result Good inhibitory activity is revealed, and the effect of most compounds is better than the comparison medicament diclazuril of commercialization.
Test case 5
Using the bactericidal activity with the part of compounds in the identical method test compound B1-B16 of test case 2, it is lived Property result is as shown in table 5.
Table 5
From the results shown in Table 5, compound of the invention is white to rice sheath blight disease, cucumber under 200mg/L concentration Powder disease and gray mold of cucumber do not show significant activity all, but the above-claimed cpd of the present invention is in 200mg/L concentration Under preferable preventive effect is shown to cucumber downy mildew.
The preferred embodiment of the present invention described in detail above, still, the present invention are not limited in above-mentioned embodiment Detail, in the range of the technology design of the present invention, a variety of simple variants can be carried out to technical scheme, this A little simple variants belong to protection scope of the present invention.
It is further to note that each particular technique feature described in above-mentioned embodiment, in not lance In the case of shield, can be combined by any suitable means, in order to avoid unnecessary repetition, the present invention to it is various can The combination of energy no longer separately illustrates.
In addition, various embodiments of the present invention can be combined randomly, as long as it is without prejudice to originally The thought of invention, it should equally be considered as content disclosed in this invention.

Claims (10)

1. a kind of diclazuril derivative, the derivative has formula (1) or the structure shown in formula (2),
Wherein, in formula (1) and formula (2),
R11And R12It is respectively selected from H, C1-4Alkyl, C1-4Alkoxy, halogen, nitro, cyano group, a bromomethyl, a chloro first Base, a fluoromethyl, trifluoromethyl and trifluoromethoxy；
R21、R22、R23And R24It is respectively selected from H, C1-4Alkyl, C1-4Alkoxy and halogen；
R3Selected from H, C1-6Alkyl, C1-6Haloalkyl, C1-6Alkoxy, C1-6Halogenated alkoxy, C1-6Alkylthio group, C1-6At least one of halogenated alkylthio, nitro, cyano group and halogen；
In formula (1), W be O orAnd
Work as R11、R21And R24For H, R22And R23For Cl, when W is O；R3It is not 4-Cl or 4-OCH3。
2. derivative according to claim 1, wherein, in formula (1) and formula (2),
R11And R12It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethoxy Base, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, fluorine, chlorine, bromine, nitro, cyano group, a bromo first Base, a chloromethyl, a fluoromethyl, trifluoromethyl and trifluoromethoxy；Preferably
R11And R12It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethoxy Base, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, fluorine, chlorine, bromine, trifluoromethyl and trifluoro methoxy Base；More preferably
R11And R12It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group and trifluoromethyl.
3. derivative according to claim 1, wherein, in formula (1) and formula (2),
R21、R22、R23And R24It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxy Base, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, fluorine, chlorine and bromine；Preferably
R21、R22、R23And R24It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group and chlorine； More preferably
R21、R22、R23And R24It is respectively selected from H, methyl, ethyl, n-propyl, isopropyl and chlorine.
4. derivative according to claim 1, wherein, in formula (1) and formula (2),
R3Selected from H, C1-4Alkyl, C1-4Haloalkyl, C1-4Alkoxy, C1-4Halogenated alkoxy, C1-4Alkylthio group, C1-4At least one of halogenated alkylthio, nitro, cyano group and halogen；
R3Selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, positive third oxygen Base, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, methyl mercapto, ethylmercapto group, positive rosickyite base, isopropyisulfanyl, positive fourth sulphur At least one of base, isobutylthio, tertiary butylthio, nitro, cyano group and halogen；More preferably
R3Selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, methoxyl group, ethyoxyl, positive third oxygen Base, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, methyl mercapto, ethylmercapto group, positive rosickyite base, isopropyisulfanyl, positive fourth sulphur At least one of base, isobutylthio, tertiary butylthio, nitro, cyano group and halogen.
5. derivative according to claim 1, wherein, the diclazuril derivative is at least one in following compound Kind；And compound A1-A28 and compound B-11-B16 have the structure shown in formula (1)；Compound C1-C12 has formula (2) institute The structure shown；
Compound A1：R11、R21And R24For H；R22And R23For Cl；R3For 2-Cl；W is O；
Compound A2：R11、R21And R24For H；R22And R23For Cl；R3For 2-Br；W is O；
Compound A-13：R11、R21And R24For H；R22And R23For Cl；R3For 2-SCH3；W is O；
Compound A4：R11、R21And R24For H；R22And R23For Cl；R3For 3-C2H5；W is O；
Compound A-45：R11、R21And R24For H；R22And R23For Cl；R3For 4-F；W is O；
Compound A6：R11、R21And R24For H；R22And R23For Cl；R3For 4-tC4H9；W is O；
Compound A7：R11、R21And R24For H；R22And R23For Cl；R3For 2,4- (tC4H9)2；W is O；
Compound A-28：R11、R21And R24For H；R22And R23For Cl；R3For 2-Cl-4-tC4H9；W is O；
Compound A9：R11、R21And R24For H；R22And R23For Cl；R3For 2-Br-4-tC4H9；W is O；
Compound A10：R11、R21And R24For H；R22And R23For Cl；R3For 2-CH3-4-tC4H9；W is O；
Compound A11：R11、R21And R24For H；R22And R23For Cl；R3For 3,5- (CH3)2；W is O；
Compound A12：R11、R21And R24For H；R22And R23For Cl；R3For 2,6-Cl2；W is O；
Compound A13：R11、R21And R24For H；R22And R23For Cl；R3For 2,5-Cl2；W is O；
Compound A14：R11、R21And R24For H；R22And R23For Cl；R3For 2,4,6-Cl3；W is O；
Compound A15：R11、R21And R24For H；R22And R23For Cl；R3For 3,4- (CH3)2；W is O；
Compound A16：R11、R21And R24For H；R22And R23For Cl；R3For 2,3-F2；W is O；
Compound A17：R11、R21And R24For H；R22And R23For Cl；R3For 3-Br-4-F；W is O；
Compound A18：R11、R21And R24For H；R22And R23For Cl；R3For 2-CH3-5-F；W is O；
Compound A19：R11、R21And R24For H；R22And R23For Cl；R3For 2-Cl-4-CH3；W is O；
Compound A20：R11、R21And R24For H；R22And R23For Cl；R3For 3,4-Cl2；W is O；
Compound A21：R11For CH3；R21And R24For H；R22And R23For Cl；R3For 2-Cl；W is O；
Compound A22：R11FortC4H9；R21And R24For H；R22And R23For Cl；R3For 2-Br；W is O；
Compound A23：R11For CF3；R21And R24For H；R22For CH3；R23For Cl；R3For 2-SCH3；W is O；
Compound A24：R11For H；R21And R24For CH3；R22And R23For Cl；R3For 2-Cl；W is O；
Compound A25：R11And R23For H；R21For CH3；R22For Cl；R24ForiCH(CH3)2；R3For 2-Br；W is O；
Compound A26：R11、R21、R22And R24For H；R23For Cl；R3For 2-NO2；W is O；
Compound B-11：R11、R21、R23And R24For H；R22For Cl；R3For 4-Cl；W is
Compound B2：R11、R21、R23And R24For H；R22For Cl；R3For 2-Cl；W is
Compound B3：R11、R21、R23And R24For H；R22For Cl；R3For 3,5- (CH3)2；W is
Compound B4：R11、R21、R23And R24For H；R22For Cl；R3For 2-CH3-5-iCH(CH3)2；W is
Compound B5：R11、R21、R23And R24For H；R22For Cl；R3For 2-SCH3；W is
Compound B-26：R11、R21、R23And R24For H；R22For Cl；R3For 4-CH3；W is
Compound B7：R11、R21、R23And R24For H；R22For Cl；R3For 2-CH3-5-F；W is
Compound B8：R11、R21、R23And R24For H；R22For Cl；R3For 3,4- (CH3)2；W is
Compound B9：R11、R21、R23And R24For H；R22For Cl；R3For 2,5-Cl2；W is
Compound B-11 0：R11、R21、R23And R24For H；R22For Cl；R3For 2-Cl-4-F；W is
Compound B-11 1：R11For CH3；R21、R23And R24For H；R22For Cl；R3For 4-Cl；W is
Compound B-11 2：R11ForiCH(CH3)2；R21、R23And R24For H；R22For Cl；R3For 3,5- (CH3)2；W is
Compound B-11 3：R11For CF3；R21、R23And R24For H；R22For Cl；R3For 2-SCH3；W is
Compound B-11 4：R11And R23For H；R21And R24For CH3；R22For Cl；R3For 2-Cl；W is
Compound B-11 5：R11And R23For H；R21For CH3；R22For Cl；R24ForiCH(CH3)2；R3For 2-Br；W is
Compound B-11 6：R11、R21And R24For H；R22And R23For Cl；R3For 2-NO2；W is
Compound C1：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2-Cl-4-CH3；
Compound C2：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,5-Cl2；
Compound C3：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2-Cl；
Compound C4：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,3-F2；
Compound C5：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 3-CH3；
Compound C6：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,4- (tC4H9)2；
Compound C7：R11、R21And R24For H；R12For CF3；R22And R23For Cl；R3For 2,6-Cl2；
Compound C8：R11、R21And R24For H；R12For ClCH2；R22And R23For Cl；R3For 4-tC4H9；
Compound C9：R11For C2H5；R12、R22And R23For Cl；R21And R24For H；R3For 4-CN；
Compound C10：R11And R24For H；R12For CN；R21For CH3；R22And R23For Cl；R3For 2,4,6-Cl3；
Compound C11：R11、R21、R23And R24For H；R12For NO2；R22For Cl；R3For 2-Cl-4-tC4H9；
Compound C12：R11、R22And R24For H；R12And R21For CH3；R23For Cl；R3For 2-CH3-4-tC4H9。
6. the diclazuril derivative in claim 1-5 described in any one is as mitochondrial succinate dehydrogenase inhibitor Using.
7. application of the diclazuril derivative in plant epiphyte resisting disease in claim 1-5 described in any one；Preferably
The plant mycosis is at least one of rice sheath blight disease, gray mold of cucumber, cucumber downy mildew and powdery mildew of cucumber.
8. a kind of bactericide for plant epiphyte resisting disease, it is characterised in that the active component of the bactericide is claim 1-5 At least one of diclazuril derivative described in middle any one, with the gross weight meter of the bactericide, it is described activity into The content divided is 0.1-100 weight %.
9. bactericide according to claim 8, wherein, the content of the active component is 1-98 weight %；Preferably 5- 90 weight %.
10. bactericide according to claim 8 or claim 9, wherein, the formulation of the bactericide is selected from hydrating agents, pulvis, breast Agent, suspending agent and granula.
CN201610387500.4A 2016-06-02 2016-06-02 Diclazuril derivative and its application and the fungicide containing the derivative Active CN107459493B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201910420685.8A CN110183386B (en) 2016-06-02 2016-06-02 Diclazuril derivative, application thereof and bactericide containing diclazuril derivative
CN201610387500.4A CN107459493B (en) 2016-06-02 2016-06-02 Diclazuril derivative and its application and the fungicide containing the derivative

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610387500.4A CN107459493B (en) 2016-06-02 2016-06-02 Diclazuril derivative and its application and the fungicide containing the derivative

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201910420685.8A Division CN110183386B (en) 2016-06-02 2016-06-02 Diclazuril derivative, application thereof and bactericide containing diclazuril derivative

Publications (2)

Publication Number Publication Date
CN107459493A true CN107459493A (en) 2017-12-12
CN107459493B CN107459493B (en) 2019-11-01

Family

ID=60544815

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201610387500.4A Active CN107459493B (en) 2016-06-02 2016-06-02 Diclazuril derivative and its application and the fungicide containing the derivative
CN201910420685.8A Active CN110183386B (en) 2016-06-02 2016-06-02 Diclazuril derivative, application thereof and bactericide containing diclazuril derivative

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201910420685.8A Active CN110183386B (en) 2016-06-02 2016-06-02 Diclazuril derivative, application thereof and bactericide containing diclazuril derivative

Country Status (1)

Country Link
CN (2) CN107459493B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113527221A (en) * 2020-04-20 2021-10-22 江苏中旗科技股份有限公司 Diclazuril derivative, application thereof and bactericide for resisting plant mycosis
CN114656415A (en) * 2021-03-23 2022-06-24 江苏中旗科技股份有限公司 Diclazuril derivative, application thereof and bactericide for resisting plant mycosis
CN115477623A (en) * 2021-06-16 2022-12-16 江苏中旗科技股份有限公司 Diclazuril derivative, application thereof and bactericide for resisting plant diseases

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4198407A (en) * 1977-05-18 1980-04-15 Hoechst Aktiengesellschaft Substituted 2-phenyl-1,2,4-triazine-3,5(2H,4H)-diones, and coccidiostatic agents containing same
US4640917A (en) * 1984-03-12 1987-02-03 Hoechst Aktiengesellschaft 2-phenyl-hexahydro-1,2,4-triazine-3,5-diones
US5256631A (en) * 1991-06-19 1993-10-26 Bayer Aktiengesellschaft Substituted 1,2,4-triazinediones, and their use
CN103554046A (en) * 2013-11-08 2014-02-05 中国农业科学院上海兽医研究所 Chicken coccidiosis preventing triazine compound

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0438209B1 (en) * 1990-01-18 1994-09-21 Nissan Chemical Industries, Limited Uracil derivatives and pesticides containing the same as active ingredient
JPH0539272A (en) * 1991-01-09 1993-02-19 Nissan Chem Ind Ltd Pyrimidinedione derivative and herbicide
JPH0525142A (en) * 1991-07-12 1993-02-02 Nissan Chem Ind Ltd Uracil derivative and noxious organism controlling agent
JP4600620B2 (en) * 1998-11-12 2010-12-15 公益財団法人相模中央化学研究所 2-anilino-4 (3H) -pyrimidinone derivatives and production intermediates, production methods thereof, and pest control agents containing them as active ingredients

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4198407A (en) * 1977-05-18 1980-04-15 Hoechst Aktiengesellschaft Substituted 2-phenyl-1,2,4-triazine-3,5(2H,4H)-diones, and coccidiostatic agents containing same
US4640917A (en) * 1984-03-12 1987-02-03 Hoechst Aktiengesellschaft 2-phenyl-hexahydro-1,2,4-triazine-3,5-diones
US5256631A (en) * 1991-06-19 1993-10-26 Bayer Aktiengesellschaft Substituted 1,2,4-triazinediones, and their use
CN103554046A (en) * 2013-11-08 2014-02-05 中国农业科学院上海兽医研究所 Chicken coccidiosis preventing triazine compound

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113527221A (en) * 2020-04-20 2021-10-22 江苏中旗科技股份有限公司 Diclazuril derivative, application thereof and bactericide for resisting plant mycosis
CN113527221B (en) * 2020-04-20 2023-06-23 江苏中旗科技股份有限公司 Dekkolii derivative, application thereof and bactericide for resisting plant mycosis
CN114656415A (en) * 2021-03-23 2022-06-24 江苏中旗科技股份有限公司 Diclazuril derivative, application thereof and bactericide for resisting plant mycosis
CN114656415B (en) * 2021-03-23 2024-01-12 江苏中旗科技股份有限公司 Dekkolii derivative, application thereof and bactericide for resisting plant mycosis
CN115477623A (en) * 2021-06-16 2022-12-16 江苏中旗科技股份有限公司 Diclazuril derivative, application thereof and bactericide for resisting plant diseases
WO2022262821A1 (en) * 2021-06-16 2022-12-22 江苏中旗科技股份有限公司 Diclazuril derivative and application thereof, and fungicide for combating plant diseases
CN115477623B (en) * 2021-06-16 2023-09-26 江苏中旗科技股份有限公司 Dekknii derivative, application thereof and bactericide for resisting plant diseases

Also Published As

Publication number Publication date
CN107459493B (en) 2019-11-01
CN110183386A (en) 2019-08-30
CN110183386B (en) 2022-07-29

Similar Documents

Publication Publication Date Title
CN102367240B (en) 1,2,3-thiadiazole mother ring-contained iminothiazolone compounds, intermediate thereof, and preparation methods and applications of compound and intermediate
WO2015074614A1 (en) Pyrazole amide compound and use thereof
CN107459493B (en) Diclazuril derivative and its application and the fungicide containing the derivative
CN104412985A (en) Phenanthrene-containing heterocycle compound and preparation method and application in resisting plant virus
CN107501169A (en) A kind of trans diarylethene LSD1 inhibitor, its preparation method and application
Yang et al. Design, synthesis, and structure–activity relationship of novel spiropyrimidinamines as fungicides against Pseudoperonospora cubensis
CN108570018B (en) Amide compound and preparation method and application thereof
CN111592533A (en) 1,2, 4-oxadiazole bipyridyl substituted benzamide compound and preparation method and application thereof
Jiang et al. Design, synthesis and antifungal activity of novel paeonol derivatives linked with 1, 2, 3-triazole moiety by the click reaction
CN102993185A (en) Preparation method and bactericidal activity of 2-methyl-4-amino-5-(substituted-1H-1,2,3-triazolyl) methylpyrimidine derivative
CN110606828A (en) Trifluoromethyl pyridine amide derivative containing chiral thioether structure and application thereof
Liu et al. Design, synthesis, and fungicidal activity of novel imidazo [4, 5‐b] pyridine derivatives
CN102285979B (en) N-(2-(substituted benzothiazol-2-aminobenzoyl)-phenyl)-substituted pyrazolecarboxamide compounds and preparation method and use thereof
Zhang et al. Copper (I)‐Catalyzed Intramolecular N‐N Coupling of Cyclopropyl O‐Acyl Ketoximes: Synthesis of Spiro‐fused Pyrazolin‐5‐ones
CN108976214B (en) Pyruvic acid dehydrogenase inhibitor and preparation method and application thereof
CN108069915A (en) A kind of pyrazinamide class compound and its preparation method and application and a kind of fungicide
Kumar et al. Synthesis of novel triazole functionalized pyridine derivatives as potential antimicrobial and anti-biofilm agents
Guan et al. Design, synthesis and antifungal activity of new substituted difluoromethylpyrimidinamine derivatives
CN112624969B (en) Quinoline derivative, preparation method thereof and application thereof in preventing and treating plant viruses and killing bacteria
PT86964B (en) 1,10-PHENANTROLINES COMPOSITION FOR THE PREPARATION OF FUNGICIDE COMPOSITION
CN105418518B (en) A kind of azophenlyene carboxylic acid ester compound and application thereof
CN110804019A (en) Amide compound and preparation method and application thereof
RU2591206C1 (en) Substituted 1-(1-tert-butyl-1h-imidazol-4-yl)-1h-1,2,3-triazoles, method for production thereof and fungicide composition based thereon
CN110903227B (en) Nitroguanidine compound and preparation and application thereof
Winfield et al. A preliminary assessment of the structure-activity relationship of benzimidazole-based anti-proliferative agents

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant