CN101652354A - insecticidal aryl isoxazoline derivatives - Google Patents
insecticidal aryl isoxazoline derivatives Download PDFInfo
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- CN101652354A CN101652354A CN200880011571A CN200880011571A CN101652354A CN 101652354 A CN101652354 A CN 101652354A CN 200880011571 A CN200880011571 A CN 200880011571A CN 200880011571 A CN200880011571 A CN 200880011571A CN 101652354 A CN101652354 A CN 101652354A
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Abstract
The present invention relates to novel aryl isoxazoline derivatives having excellent insecticidal activity as insecticides and represented by the formula ( I ): and their use as insecticides and acarizides.
Description
The present invention relates to new aryl isoxazoline derivatives and as the purposes of insecticide and miticide (acarizide).
The known pest control agent that can be used as of benzamide compounds that isoxazoline replaces is described in WO2005/085216.
Be have the more more broad spectrum new compound of effective active of exploitation as sterilant, the extensive studies by going deep into, the contriver has now found that new aryl isoxazoline derivatives, it has more remarkable activity, wide spectrum and have security more, in addition, it is also to obtaining the insect performance drug effect to the resistance of organophosphorus medicament and amino formate medicament.
The compounds of this invention is represented by following formula (I):
Wherein
A represents C or N;
R represents alkyl or haloalkyl;
X can be identical or different, and it represents Cl, Br, F, I, haloalkyl, nitro, alkyl, alkoxyl group, cyano group, halogenated alkoxy, alkyl sulphinyl, alkyl sulfenyl (alkylsulfenyl), alkyl sulphonyl, haloalkyl sulfinyl, haloalkyl sulfenyl, halogenated alkyl sulfonyl, amino, amido, alkoxycarbonyl amino, halogenated alkyl carbonyl amino, halo alkoxy carbonyl amino, alkyl sulfonyl-amino, halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Y can be identical or different, and it represents halogen, haloalkyl, nitro, alkyl, alkoxyl group, cyano group, halogenated alkoxy, alkyl sulphinyl, alkyl sulfenyl, alkyl sulphonyl, haloalkyl sulfinyl, haloalkyl sulfenyl, halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, amido, alkoxycarbonyl amino, halogenated alkyl carbonyl amino, halo alkoxy carbonyl amino, alkyl sulfonyl-amino or halogenated alkyl sulfonyl amino; Or two adjacent Y form an optional substituted ring with the carbon atom that they connected;
L represents 0,1,2,3,4 or 5;
M represents 0,1,2,3 or 4;
N represents 1,2 or 3;
R
1And R
2Represent hydrogen, alkyl, optional substituted cycloalkyl, haloalkyl, cyano group, alkoxy carbonyl, alkenyl or alkynyl, perhaps R independently of one another
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, alkyl, optional substituted cycloalkyl, haloalkyl, cyano group, thiazolinyl, alkynyl, alkyl-carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, alkyl-carbonyl, alkylthio carbonyl, halogenated alkyl carbonyl, halogenated alkylthio carbonyl, alkyl amino-carbonyl, alkylamino thiocarbonyl, dialkyl amino carbonyl, dialkyl amido thiocarbonyl, alkoxy amino carbonyl, alkoxyl group thiocarbonyl, alkoxy amino thiocarbonyl, alkoxy carbonyl, thio alkoxy carbonyl, thio alkoxy thiocarbonyl,
Alkyl sulphonyl or halogenated alkyl sulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form 3 yuan to 6 yuan rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
In one embodiment, formula (I) compound is contained in the present invention, wherein
A represents C,
R represents haloalkyl,
R
3Represent CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical that is selected from following group: furyl, thienyl, pyrryl, isoxazolyl, pyrazolyl, oxazolyl, Evil thiazolyl (oxathiazolyl), imidazolyl, triazolyl, oxadiazole base, thiadiazolyl group, tetrazyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, indyl, benzoxazolyl, quinolyl; And
X, Y, l, m, n, R
1, R
2, R
4As defined above, define in one of perhaps preferred as defined herein or particularly preferred embodiment.
In another embodiment, formula (I) compound is contained in the present invention, wherein
A represents C,
R represents haloalkyl,
L represents 3,
X, Y, l, m, n, R
1, R
2, R
3, R
4As defined above, define in one of perhaps preferred as defined herein or particularly preferred embodiment, condition is:
(1) identical and when representing F, Cl or Br, as two X if the 3rd X then do not represent F, CH at 4-position bonding
3, CF
3, OH, NH
2, NO
2, CN, OCH
3, OCH
2CH
3, O-n-propyl, O-CHF
2Or OCF
3,
Or (2) work as R
4When representing another substituting group except that the methyl carbonyl, if X at 5-position bonding, does not then represent CF
3,
Or (3) when on behalf of the X of Br and another 3-position, the X of a 5-position represent F or Cl, and then the 3rd X in the 4-position do not represent OCH
3
In one embodiment of the present invention, each compound is represented by formula (Ia)
Wherein
A represents C or N, and it all can be substituted basic Y separately and replace;
R represents alkyl or haloalkyl;
X can be identical or different, and it represents halogen, haloalkyl, nitro, alkyl, alkoxyl group, cyano group, halogenated alkoxy, alkyl sulphinyl, alkyl sulfenyl, alkyl sulphonyl, haloalkyl sulfinyl, haloalkyl sulfenyl, halogenated alkyl sulfonyl, amino, amido, alkoxycarbonyl amino, halogenated alkyl carbonyl amino, halo alkoxy carbonyl amino, alkyl sulfonyl-amino, halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Z or Y can be identical or different, and it represents halogen, haloalkyl, nitro, alkyl, alkoxyl group, cyano group, halogenated alkoxy, alkyl sulphinyl, alkyl sulfenyl, alkyl sulphonyl, haloalkyl sulfinyl, haloalkyl sulfenyl, halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, amido, alkoxycarbonyl amino, halogenated alkyl carbonyl amino, halo alkoxy carbonyl amino, alkyl sulfonyl-amino or halogenated alkyl sulfonyl amino;
L represents 0,1,2,3,4 or 5;
M represents 0,1 or 2;
N represents 1,2 or 3;
P represents 0,1,2,3 or 4;
R
1And R
2Represent hydrogen, alkyl, optional substituted cycloalkyl, haloalkyl, cyano group, alkoxy carbonyl, alkenyl or alkynyl, perhaps R independently of one another
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, alkyl, optional substituted cycloalkyl, haloalkyl, cyano group, thiazolinyl, alkynyl, alkyl-carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, alkyl-carbonyl, alkylthio carbonyl, halogenated alkyl carbonyl, halogenated alkylthio carbonyl, alkyl amino-carbonyl, alkylamino thiocarbonyl, dialkyl amino carbonyl, dialkyl amido thiocarbonyl, alkoxy amino carbonyl, alkoxyl group thiocarbonyl, alkoxy amino thiocarbonyl, alkoxy carbonyl, thio alkoxy carbonyl, thio alkoxy thiocarbonyl,
Alkyl sulphonyl or halogenated alkyl sulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form 3 yuan to 6 yuan rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
Formula (I) compound can obtain by the following stated preparation method (a) to (d).
Preparation method (a):
A kind of method for preparing The compounds of this invention, this method comprise the step of formula (II) compound and the reaction of formula (III) compound:
Wherein A, Y, m, n, R
1, R
2, R
3And R
4Definition as above, and Hal represents halogen,
Wherein R, X and l definition as above.
Preparation method (b):
A kind of method for preparing The compounds of this invention, this method comprise the step of formula (IV) compound and the reaction of formula V compound:
Wherein A, R, X, l, Y, m, n, R
1, R
2And R
3Define as above,
R
4-L?(V)
R wherein
4Define as above, and L represents halogen, alkylsulfonyloxy, aryl-sulfonyl oxygen or alkyl carbon acyloxy.
Preparation method (c)
A kind of method for preparing The compounds of this invention, this method comprise the step of formula (IV) compound and the reaction of formula (VII) compound:
Wherein A, R, X, l, Y, m, n, R
1, R
2And R
4Define as above,
R
3-L??(VII)
R wherein
3Define as above, and L represents halogen, alkylsulfonyloxy, aryl-sulfonyl oxygen or alkyl carbon acyloxy.
Preparation method (d)
A kind of method for preparing The compounds of this invention, this method comprise the step of formula (VIII) compound and the reaction of formula (IX) compound:
Wherein A, R, X, l, Y, m, n and L define as above,
R
3-NH-R
4????(IX)
R wherein
3And R
4Definition as above.
According to the present invention, the aryl isoxazoline derivatives of above-mentioned formula (I) has effectively insect and acarid activity extremely extremely.
Term used herein " alkyl " is meant the C of straight or branched
1-12Alkyl comprises for example ethyl, methyl, n-propyl or sec.-propyl, normal-butyl, isobutyl-, sec-butyl or the tertiary butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, positive decyl, n-undecane base and dodecyl, and preferably refers to C
1-6Alkyl.In the group that has as the alkyl of its molecular formula part, this moieties can have and above-mentioned " alkyl " described identical implication.Described alkyl can be unsubstituted or is replaced by at least one suitable substituents.
Term " amido " is meant for example alkyl-carbonyl-amino, cycloalkyl amino carbonyl and benzamido, and wherein moieties can have and above-mentioned " alkyl " described identical implication, and cycloalkyl moiety can have and following identical implication.Amido can be unsubstituted or is replaced by at least one suitable substituents.
Halogen in term " halogen " and the group that replaced by halogen is partly represented fluorine, chlorine, bromine and iodine.Preferred halogen is fluorine, chlorine and bromine.
Term " cycloalkyl " is meant C
3-8Cycloalkyl comprises for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl and ring octyl group, and preferably refers to C
3-7Cycloalkyl.Described group of naphthene base can be unsubstituted or is replaced by at least one suitable substituents.
Term " thiazolinyl " is meant C
2-5Thiazolinyl comprises for example vinyl, allyl group, 1-propenyl, 1-(or 2-or 3-) butenyl and 1-pentenyl, and preferably refers to C
2-4Thiazolinyl.Described thiazolinyl can be unsubstituted or is replaced by at least one suitable substituents.
" cyclic group " preferably refers to contain the ring of 3-6 carbon atom.This group is preferably aromatic ring, most preferably is phenyl ring.Described cyclic group can be unsubstituted or is replaced by at least one suitable substituents.
" heterocyclic radical " preferably refers to contain heteroatomic 5 yuan or 6 yuan of heterocyclic radicals that at least one is selected from N, O or S, and described heterocyclic radical also refer to can be by benzo-fused annelated heterocycles base.Described heterocyclic radical can be unsubstituted or is replaced by at least one suitable substituents.
The specific examples of " heterocyclic radical " comprises furyl, thienyl, pyrryl, isoxazolyl, pyrazolyl, oxazolyl, Evil thiazolyl, imidazolyl, triazolyl, oxadiazole base, thiadiazolyl group, tetrazyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, indyl, benzoxazolyl, quinolyl etc.
Suitable substituents comprises for example following chemical group; promptly amino; hydroxyl; halogen; nitro; cyano group; isocyano-; sulfydryl; isothiocyano; carboxyl; carboxamide (carbonamide); SF5; amino-sulfonyl; alkyl; cycloalkyl; thiazolinyl; cycloalkenyl group; alkynyl; monoalkyl-amino; dialkyl-7-amino; N-alkyloyl-amino; alkoxyl group; alkene oxygen base; alkynyloxy group; cycloalkyloxy; cyclenes oxygen base; alkoxyl group-carbonyl; alkene oxygen base-carbonyl; alkynyloxy group-carbonyl; aryloxycarbonyl; alkyloyl; thiazolinyl-carbonyl; alkynyl-carbonyl; aryl-carbonyl; alkylthio; cycloalkylthio; alkenylthio group; the cyclenes sulfenyl; the alkynes sulfenyl; the alkyl sulfenyl; alkyl sulphinyl (two kinds of enantiomeric forms that comprise alkyl sulphinyl); alkyl sulphonyl; monoalkyl-amino-sulfonyl; the dialkyl-7-amino alkylsulfonyl; the alkylphosphine oxide base; alkylphosphines acyl group (two kinds of enantiomeric forms that comprise alkylphosphine oxide base and alkylphosphines acyl group respectively); N-alkyl-aminocarboxyl; N, N-dialkyl-7-amino carbonyl; N-alkyloyl-aminocarboxyl; N-alkyloyl-N-alkyl-aminocarboxyl; aryl; aryloxy; phenmethyl; benzyloxy; benzylthio-; arylthio; virtue is amino; benzyl amino; heterocyclic radical and trialkylsilkl.Also comprise further substituted substituting group, for example alkoxyalkyl, alkylthio alkyl, alkylthio alkoxyl group, alkoxyl group alkoxyl group, styroyl, benzyloxy, haloalkyl, halogenated alkoxy, halogenated alkylthio, haloalkane acyl group, halogenated alkyl carbonyl, halo alkoxy carbonyl, halogenated alkoxy alkoxyl group, halogenated alkoxy alkylthio, halogenated alkoxy alkyloyl, halogenated alkoxy alkyl.
In formula of the present invention (I) compound, the preferred wherein compound of each group as giving a definition
A represents C or N;
R represents C
1-6Alkyl or C
1-6Haloalkyl;
X can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, amino, C
1-6Alkyl-carbonyl, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino, C
1-6Halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Y can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, C
1-4Alkyl-carbonyl-amino, benzoyl-amido, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino or C
1-6Halogenated alkyl sulfonyl amino;
L represents 0,1,2 or 3;
M represents 0,1 or 2;
N represents 1;
R
1And R
2Represent hydrogen, C independently of one another
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
1-6Alkoxy carbonyl, C
2-4Thiazolinyl or C
2-4Alkynyl, perhaps R
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, C
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
2-4Thiazolinyl, C
2-4Alkynyl, C
1-6Alkynyl carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, C
1-6Alkyl-carbonyl, C
1-6Alkylthio carbonyl, C
1-6Halogenated alkyl carbonyl, C
1-6Halogenated alkylthio carbonyl, C
1-6Alkyl amino-carbonyl, C
1-6Alkylamino thiocarbonyl, C
2-8(sum of carbon) dialkyl amino carbonyl, C
2-8(sum of carbon) dialkyl amido thiocarbonyl, C
1-6Alkoxy amino carbonyl, C
1-6Alkoxyl group thiocarbonyl, C
1-6Alkoxy amino thiocarbonyl, C
1-6Alkoxy carbonyl, sulfo--C
1-6Alkoxy carbonyl, sulfo--C
1-6The alkoxyl group thiocarbonyl,
C
1-6Alkyl sulphonyl or C
1-6Haloalkyl-alkylsulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form one 4 yuan or 5 yuan of rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
In another preferred embodiment of the present invention, this compound is by wherein formula (Ia) expression of each group as giving a definition
The A representative can be substituted the C that basic Y replaces;
R represents C
1-6Alkyl or C
1-6Haloalkyl;
X can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl-sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, amino, C
1-6Alkyl-carbonyl, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino, C
1-6Haloalkyl-sulfuryl amino, hydroxyl or sulfydryl;
Z or Y can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, C
1-4Alkyl-carbonyl-amino, benzoyl-amido, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino or C
1-6Halogenated alkyl sulfonyl amino;
L represents 0,1,2 or 3;
M represents 0,1 or 2;
N represents 1;
P represents 0,1,2,3 or 4;
R
1And R
2Represent hydrogen, C independently of one another
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
1-6Alkoxy carbonyl, C
2-4Thiazolinyl or C
2-4Alkynyl, perhaps R
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, C
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
2-4Thiazolinyl, C
2-4Alkynyl, C
1-6Alkynyl carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, C
1-6Alkyl-carbonyl, C
1-6Alkylthio carbonyl, C
1-6Halogenated alkyl carbonyl, C
1-6Halogenated alkylthio carbonyl, C
1-6Alkyl amino-carbonyl, C
1-6Alkylamino thiocarbonyl, C
2-8(sum of carbon) dialkyl amino carbonyl, C
2-8(sum of carbon) dialkyl amido thiocarbonyl, C
1-6Alkoxy amino carbonyl, C
1-6Alkoxyl group thiocarbonyl, C
1-6Alkoxy amino thiocarbonyl, C
1-6Alkoxy carbonyl, sulfo--C
1-6Alkoxy carbonyl, sulfo--C
1-6The alkoxyl group thiocarbonyl,
C
1-6Alkyl sulphonyl or C
1-6Haloalkyl-alkylsulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form one 4 yuan or 5 yuan of rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
In another kind of preferred embodiment of the present invention, this compound is by wherein formula (Ia) expression of each group as giving a definition
The A representative can be substituted the N that basic Y replaces;
R represents C
1-6Alkyl or C
1-6Haloalkyl;
X can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl-sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, amino, C
1-6Alkyl-carbonyl, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino, C
1-6Haloalkyl-sulfuryl amino, hydroxyl or sulfydryl;
Z or Y can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, C
1-4Alkyl-carbonyl-amino, benzoyl-amido, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino or C
1-6Halogenated alkyl sulfonyl amino;
L represents 0,1,2 or 3;
M represents 0,1 or 2;
N represents 1;
P represents 0,1,2,3 or 4;
R
1And R
2Represent hydrogen, C independently of one another
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
1-6Alkoxy carbonyl, C
2-4Thiazolinyl or C
2-4Alkynyl, perhaps R
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, C
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
2-4Thiazolinyl, C
2-4Alkynyl, C
1-6Alkynyl carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, C
1-6Alkyl-carbonyl, C
1-6Alkylthio carbonyl, C
1-6Halogenated alkyl carbonyl, C
1-6Halogenated alkylthio carbonyl, C
1-6Alkyl amino-carbonyl, C
1-6Alkylamino thiocarbonyl, C
2-8(sum of carbon) dialkyl amino carbonyl, C
2-8(sum of carbon) dialkyl amido thiocarbonyl, C
1-6Alkoxy amino carbonyl, C
1-6Alkoxyl group thiocarbonyl, C
1-6Alkoxy amino thiocarbonyl, C
1-6Alkoxy carbonyl, sulfo--C
1-6Alkoxy carbonyl, sulfo--C
1-6The alkoxyl group thiocarbonyl,
C
1-6Alkyl sulphonyl or C
1-6Haloalkyl-alkylsulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form one 4 yuan or 5 yuan of rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
In those formulas (I) compound, the preferred especially wherein compound of each group as giving a definition
A represents C or N;
R represents C
1-4Alkyl or C
1-4Haloalkyl;
X can be identical or different, and it represents halogen, C
1-4Haloalkyl, nitro, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group, C
1-4Halogenated alkoxy, C
1-4Alkyl sulphinyl, C
1-4Alkyl sulfenyl, C
1-4Alkyl sulphonyl, C
1-4Haloalkyl sulfinyl, C
1-4Haloalkyl sulfenyl, C
1-4Halogenated alkyl sulfonyl, amino, C
1-4Alkyl-carbonyl, C
1-4Alkoxycarbonyl amino, C
1-4Halogenated alkyl carbonyl amino, C
1-4Halo alkoxy carbonyl amino, C
1-4Alkyl sulfonyl-amino, C
1-4Halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Y can be identical or different, and it represents halogen, C
1-4Haloalkyl, nitro, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group, C
1-4Halogenated alkoxy, C
1-4Alkyl sulphinyl, C
1-4Alkyl sulfenyl, C
1-4Alkyl sulphonyl, C
1-4Haloalkyl sulfinyl, C
1-4Haloalkyl sulfenyl, C
1-4Halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, C
1-4Alkyl-carbonyl-amino, benzoyl-amido, C
1-4Alkoxycarbonyl amino, C
1-4Halogenated alkyl carbonyl amino, C
1-4Halo alkoxy carbonyl amino, C
1-4Alkyl sulfonyl-amino or C
1-4Halogenated alkyl sulfonyl amino;
L represents 0,1,2 or 3;
M represents 1;
N represents 1;
R
1And R
2Represent hydrogen, C independently of one another
1-4Alkyl, optional substituted C
3-6Cycloalkyl, C
1-4Haloalkyl, cyano group, C
1-4Alkoxy carbonyl, C
2-3Thiazolinyl or C
2-3Alkynyl, perhaps R
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, C
1-4Alkyl, optional substituted C
3-6Cycloalkyl, C
1-4Haloalkyl, cyano group, C
2-3Thiazolinyl, C
2-3Alkynyl, C
1-4Alkyl-carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, C
1-4Alkyl-carbonyl, C
1-4Alkylthio carbonyl, C
1-4Halogenated alkyl carbonyl, C
1-4Halogenated alkylthio carbonyl, C
1-4Alkyl amino-carbonyl, C
1-4Alkylamino thiocarbonyl, C
2-6(sum of carbon) dialkyl amino carbonyl, C
2-6(sum of carbon) dialkyl amido thiocarbonyl, C
1-4Alkoxy amino carbonyl, C
1-4Alkoxyl group thiocarbonyl, C
1-4Alkoxy amino thiocarbonyl, C
1-4Alkoxy carbonyl, sulfo--C
1-4Alkoxy carbonyl, sulfo--C
1-4The alkoxyl group thiocarbonyl,
C
1-4Alkyl sulphonyl or C
1-4Haloalkyl-alkylsulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form one 4 yuan or 5 yuan of rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
In another particularly preferred embodiment of the present invention, this compound is by wherein formula (Ia) expression of each group as giving a definition
The A representative can be substituted the C that basic Y replaces;
R represents C
1-4Alkyl or C
1-4Haloalkyl;
X can be identical or different, and it represents halogen, C
1-4Haloalkyl, nitro, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group, C
1-4Halogenated alkoxy, C
1-4Alkyl sulphinyl, C
1-4Alkyl sulfenyl, C
1-4Alkyl sulphonyl, C
1-4Haloalkyl sulfinyl, C
1-4Haloalkyl sulfenyl, C
1-4Halogenated alkyl sulfonyl, amino, C
1-4Alkyl-carbonyl, C
1-4Alkoxycarbonyl amino, C
1-4Halogenated alkyl carbonyl amino, C
1-4Halo alkoxy carbonyl amino, C
1-4Alkyl sulfonyl-amino, C
1-4Halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Z or Y can be identical or different, and it represents halogen, C
1-4Haloalkyl, nitro, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group, C
1-4Halogenated alkoxy, C
1-4Alkyl sulphinyl, C
1-4Alkyl sulfenyl, C
1-4Alkyl sulphonyl, C
1-4Haloalkyl sulfinyl, C
1-4Haloalkyl sulfenyl, C
1-4Halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, C
1-4Alkyl-carbonyl-amino, benzoyl-amido, C
1-4Alkoxycarbonyl amino, C
1-4Halogenated alkyl carbonyl amino, C
1-4Halo alkoxy carbonyl amino, C
1-4Alkyl sulfonyl-amino or C
1-4Halogenated alkyl sulfonyl amino;
L represents 0,1,2 or 3;
M is 0 or 1;
N is 1;
P represents 0,1 or 3;
R
1And R
2Represent hydrogen, C independently of one another
1-4Alkyl, optional substituted C
3-6Cycloalkyl, C
1-4Haloalkyl, cyano group, C
1-4Alkoxy carbonyl, C
2-3Thiazolinyl or C
2-3Alkynyl, perhaps R
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, C
1-4Alkyl, optional substituted C
3-6Cycloalkyl, C
1-4Haloalkyl, cyano group, C
2-3Thiazolinyl, C
2-3Alkynyl, C
1-4Alkyl-carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, C
1-4Alkyl-carbonyl, C
1-4Alkylthio carbonyl, C
1-4Halogenated alkyl carbonyl, C
1-4Halogenated alkylthio carbonyl, C
1-4Alkyl amino-carbonyl, C
1-4Alkylamino thiocarbonyl, C
2-6(sum of carbon) dialkyl amino carbonyl, C
2-6(sum of carbon) dialkyl amido thiocarbonyl, C
1-4Alkoxy amino carbonyl, C
1-4Alkoxyl group thiocarbonyl, C
1-4Alkoxy amino thiocarbonyl, C
1-4Alkoxy carbonyl, sulfo--C
1-4Alkoxy carbonyl, sulfo--C
1-4The alkoxyl group thiocarbonyl,
C
1-4Alkyl sulphonyl or C
1-4Haloalkyl-alkylsulfonyl, wherein R
5Definition as above; Perhaps
R
3And R
4Can form one 4 yuan or 5 yuan of rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
In a kind of equal preferred embodiment of the present invention, this compound is by wherein formula (I) expression of each group as giving a definition
A represents C;
R represents CF
3
X can be identical or different, and it represents Cl, F, I, Br, CF
3, NO
2, C
1-4Alkoxyl group, cyano group, C
1-4Fluoroalkyloxy, C
1-4Alkyl sulphonyl, amino, C
1-4Alkyl-carbonyl, hydroxyl or sulfydryl;
Y can be identical or different, and it represents Cl, F, I, Br, CF
3, NO
2, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group, C
1-4Halogenated alkoxy, hydroxyl, amino;
L represents 1,2 or 3;
M represents 1;
N represents 1;
R
1And R
2Represent hydrogen or C independently of one another
1-4Alkyl;
R
3Represent hydrogen, C
1-4Alkyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical, described heterocyclic radical is selected from furyl, thienyl, pyrryl, isoxazolyl, pyrazolyl, oxazolyl, Evil thiazolyl, imidazolyl, triazolyl, oxadiazole base, thiadiazolyl group, tetrazyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, indyl, benzoxazolyl, quinolyl; And
R
4Represent C
1-4Alkyl-carbonyl, vinyl carbonyl, C
1-4Alkylthio carbonyl, C
1-4Halogenated alkyl carbonyl, C
1-4Alkyl amino-carbonyl, two-(C
1-C
2) alkyl amino-carbonyl, C
1-4Alkoxy amino carbonyl, C
1-4Alkoxy carbonyl, sulfo--C
1-4Alkoxy carbonyl, C
1-4Alkyl sulphonyl ,-C (O) R
5, C (S) R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical that is selected from following group: furyl, thienyl, pyrryl, isoxazolyl, pyrazolyl, oxazolyl, Evil thiazolyl, imidazolyl, triazolyl, oxadiazole base, thiadiazolyl group, tetrazyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, indyl, benzoxazolyl, quinolyl.
In another kind of particularly preferred embodiment of the present invention, this compound is by wherein formula (Ia) expression of each group as giving a definition
The A representative can be substituted the N that basic Y replaces;
R represents C
1-4Alkyl or C
1-4Haloalkyl;
X can be identical or different, and it represents halogen, C
1-4Haloalkyl, nitro, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group, C
1-4Halogenated alkoxy, C
1-4Alkyl sulphinyl, C
1-4Alkyl sulfenyl, C
1-4Alkyl sulphonyl, C
1-4Haloalkyl sulfinyl, C
1-4Haloalkyl sulfenyl, C
1-4Halogenated alkyl sulfonyl, amino, C
1-4Alkyl-carbonyl, C
1-4Alkoxycarbonyl amino, C
1-4Halogenated alkyl carbonyl amino, C
1-4Halo alkoxy carbonyl amino, C
1-4Alkyl sulfonyl-amino, C
1-4Halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Z or Y can be identical or different, and it represents halogen, C
1-4Haloalkyl, nitro, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group, C
1-4Halogenated alkoxy, C
1-4Alkyl sulphinyl, C
1-4Alkyl sulfenyl, C
1-4Alkyl sulphonyl, C
1-4Haloalkyl sulfinyl, C
1-4Haloalkyl sulfenyl, C
1-4Halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, C
1-4Alkyl-carbonyl-amino, benzoyl-amido, C
1-4Alkoxycarbonyl amino, C
1-4Halogenated alkyl carbonyl amino, C
1-4Halo alkoxy carbonyl amino, C
1-4Alkyl sulfonyl-amino or C
1-4Halogenated alkyl sulfonyl amino;
L represents 0,1,2 or 3;
M is 0 or 1;
N is 1;
P represents 0,1 or 3
R
1And R
2Represent hydrogen, C independently of one another
1-4Alkyl, optional substituted C
3-6Cycloalkyl, C
1-4Haloalkyl, cyano group, C
1-4Alkoxy carbonyl, C
2-3Thiazolinyl or C
2-3Alkynyl, perhaps R
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, C
1-4Alkyl, optional substituted C
3-6Cycloalkyl, C
1-4Haloalkyl, cyano group, C
2-3Thiazolinyl, C
2-3Alkynyl, C
1-4Alkyl-carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, C
1-4Alkyl-carbonyl, C
1-4Alkylthio carbonyl, C
1-4Halogenated alkyl carbonyl, C
1-4Halogenated alkylthio carbonyl, C
1-4Alkyl amino-carbonyl, C
1-4Alkylamino thiocarbonyl, C
2-6(sum of carbon) dialkyl amino carbonyl, C
2-6(sum of carbon) dialkyl amido thiocarbonyl, C
1-4Alkoxy amino carbonyl, C
1-4Alkoxyl group thiocarbonyl, C
1-4Alkoxy amino thiocarbonyl, C
1-4Alkoxy carbonyl, sulfo--C
1-4Alkoxy carbonyl, sulfo--C
1-4The alkoxyl group thiocarbonyl,
C
1-4Alkyl sulphonyl or C
1-4Haloalkyl-alkylsulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form one 4 yuan or 5 yuan of rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and the carbon atom that wherein constitutes this ring can be replaced by ketone group or thioketones base.
Another aspect of the present invention relates to a kind of like this pharmaceutical composition, this pharmaceutical composition contains at least a The compounds of this invention, the compound of one of embodiment that preferred at least a this paper limited, the more preferably compound of the preferred embodiment that at least a this paper limited, and the compound of the particularly preferred embodiment that at least a this paper limited most preferably, this pharmaceutical composition can be used for resisting zooparasite.
Formula (I) compound has asymmetric carbon, and thereby contains optically active isomer.In addition, the polymorphic form that The compounds of this invention can be different or as the mixture of different polymorphic forms and exist.The invention provides two kinds in pure polymorphic form and polymorphic form mixture, and it can be used according to the invention.
When using for example 4-(acetylamino methyl)-N-hydroxybenzene carboxylic imino-chlorine and 1,3-two chloro-5-[1-(trifluoromethyl) vinyl] benzene is during as raw material, and above-mentioned preparation method (a) can be represented by following reaction scheme.
When using for example 1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl }-methylamine and Acetyl Chloride 98Min. are during as raw material, and above-mentioned preparation method (b) can be represented by following reaction scheme.
When using for example N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } ethanamide and methyl iodide are during as raw material, and above-mentioned preparation method (c) can be represented by following reaction scheme.
When using for example 3-[3-bromo-4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole and thioacetamide are during as raw material, and above-mentioned preparation method (d) can be represented by following reaction scheme.
Formula (II) compound that is used as raw material among the preparation method (a) is new compound and can obtains by compound and the reaction of a kind of halogenating agent that is expressed from the next:
Wherein A, Y, m, n, R
1, R
2, R
3And R
4Definition as above.
Many above-mentioned formulas (X) compound is new compound and can obtains by the compound that is expressed from the next and oxyamine or its reactant salt:
Wherein A, Y, m, n, R
1, R
2, R
3And R
4Definition as above.
Many above-mentioned formulas (XI) compound is new compound and can obtains according to for example method described in the WO 2004/067522.
Typical reaction method is represented by following scheme:
Wherein A, Y and m definition as above.
The example that is used as the 4-cyanobenzaldehyde of above-mentioned reaction scheme raw material comprises 4-cyanobenzaldehyde, 4-cyano group-2-fluorobenzaldehyde, 2-chloro-4-cyanobenzaldehyde, 2-bromo-4-cyanobenzaldehyde, 4-cyano group-2-benzaldehyde iodine and 5-formyl radical pyridine-2-formonitrile HCN.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of the starting compound of above-mentioned reaction method scheme is 4-formyl radical naphthalene-1-formonitrile HCN.
Above-mentioned formula (XI) compound also can synthesize by the alternative approach of being represented by following reaction scheme:
Wherein A, Y and m definition as above.
Be used as the example of the 4-tolyl aldehyde of above-mentioned reaction scheme raw material, comprise 3-fluoro-4-tolyl aldehyde, 3-chloro-4-tolyl aldehyde, 3-bromo-4-tolyl aldehyde, 4-methyl-3-benzaldehyde iodine, 3-methoxyl group-4-tolyl aldehyde, 4-methyl-3-nitro phenyl aldehyde and 6-methyl nicotine aldehyde.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of the starting compound of above-mentioned reaction method scheme is 4-methylnaphthalene-1-formaldehyde.
The example for preparing the halogenating agent in above-mentioned formula (II) compound comprises, for example chlorine, bromine, iodine, N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, 1,3-two chloro-5,5-T10,1,3-two bromo-5,5-T10, benzyltrimethylammon.um tetrachloro iodide (benzyltrimethylammonium tetrachloroiodate), clorox etc.
The representative instance that is used as formula (II) compound of raw material among the preparation method (a) comprises 4-(acetylamino methyl)-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-N-hydroxy-3-methyl benzene carboxylic imino-chlorine, 4-(acetylamino methyl)-3-fluoro-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-3-chloro-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-3-bromo-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-N-hydroxyl-3-iodobenzene carboxylic imino-chlorine and 4-(acetylamino methyl)-N-hydroxyl-3-oil of mirbane carboxylic imino-chlorine.
When two adjacent Y form a randomly substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (II) compound is N-({ 4-[(oxyimino) methyl] naphthalene-1-yl } methyl) ethanamide.
Formula (III) compound as another raw material among the preparation method (a) is contained the known compound described in for example following document: Journal of Organic Chemistry, 1991, the 56 volumes, 7336-7340 page or leaf and 1994, the 59th volume, the 2898-2901 page or leaf; Journal of FluorineChemistry, 1999, the 95 volumes, 167-170 page or leaf; With WO 2005/05085216.Described compound can synthesize by the method for describing in these publications.The representative instance of formula (III) compound comprises [1-(trifluoromethyl) vinyl] benzene, 1,3-two fluoro-5-[1-(trifluoromethyl) vinyl] benzene, 1-chloro-3-[1-(trifluoromethyl) vinyl] benzene, 1,3-two chloro-5-[1-(trifluoromethyl) vinyl] benzene, 1-trifluoromethyl-3-[1-(trifluoromethyl) vinyl] benzene, 1-trifluoromethyl-4-[1-(trifluoromethyl) vinyl] benzene, 1, two (trifluoromethyl)-5-[1-(trifluoromethyl) vinyl of 3-] benzene, 1,3-two bromo-5-[1-(trifluoromethyl) vinyl] benzene, 1,2,3-three chloro-5-[1-(trifluoromethyl) vinyl] benzene and 1-fluoro-2-(trifluoromethyl)-4-[1-(trifluoromethyl) vinyl] benzene.
Preparation method (a) can be according to WO 2004/018410, WO 2005/085216, Tetrahedron (2000), the 56th volume, and method described in the 1057-1064 page or leaf is implemented.
Preparation method's (a) reaction can be carried out in a kind of suitable diluent, the example of the described thinner that can use in the method for example comprises, aliphatic hydrocrbon (hexane for example, hexanaphthene, heptane), aromatic hydrocarbon (benzene for example, toluene, dimethylbenzene, chlorobenzene), alcohol (methyl alcohol for example, ethanol, Virahol), ether (diethyl ether for example, dibutyl ether, glycol dimethyl ether (DME), tetrahydrofuran (THF), dioxane), acid amides (dimethyl formamide (DMF) for example, N,N-DIMETHYLACETAMIDE (DMA), N-Methyl pyrrolidone), nitrile (acetonitrile for example, propionitrile), methyl-sulphoxide (DMSO), water, or its mixture.
Preparation method's (a) reaction can use a kind of following alkali to carry out: alkali metal base comprises for example yellow soda ash, salt of wormwood, sodium bicarbonate, saleratus, sodium acetate, potassium acetate, sodium methylate, sodium ethylate and potassium tert.-butoxide; And organic bases, comprise triethylamine, diisopropylethylamine, Tributylamine, N-methylmorpholine, N, accelerine, N, N-Diethyl Aniline, the 4-tertiary butyl-N, accelerine, pyridine, picoline, lutidine, diazabicyclo undecylene, diazabicyclo octane and imidazoles.
Preparation method's (a) reaction can be carried out in the temperature range of non-constant width.Usually, this reaction can be carried out under about-78 ℃ to 200 ℃ temperature, preferred-10 ℃ to about 150 ℃.This reaction is preferably carried out under normal pressure, but it also can carry out under the pressure that improves or reduce.Reaction times can be 0.1-72 hour, preferred 1-24 hour.
In implementing preparation method (a), for example, 1 mole of formula (II) compound and 1-2 mole formula (III) compound and 1 mole or excessive slightly a kind of alkali for example can be reacted among the DMF at thinner, obtain the target compound of formula (I).
Formula (IV) compound as raw material among the preparation method (b) is a new compound, and (e) to (k) obtains by the following method.
Preparation method (e) (R in formula (IV)
3Representing hydrogen and n is 1 o'clock):
Described method is: make the reaction of formula (XII) compound and halogenating agent to obtain formula (XIII) compound, gained compound and potassium phthalimide react and obtain formula (XIV) compound, and hydrolysis gained compound,
Wherein A, R, X, l, Y, m, R
1And R
2Define as above,
Wherein A, R, X, l, Y, m, R
1And R
2Definition as above, and Hal represents halogen,
Wherein A, R, X, l, Y, m, R
1And R
2Definition as above.
Preparation method (f)
Described method is: make the reaction of above-mentioned formula (XIII) compound and formula (XV) compound:
R
3-NH
2??(XV)
R wherein
3Definition as above.
(n represents 1 and R to preparation method (g) in formula (IV)
1And R
2When representing hydrogen):
Described method is: the reduction of formula (XVI) compound is obtained formula (XVII) compound, and gained compound and methylsulfonyl chloride or halogenating agent react and obtain formula (XVIII) compound, make the reaction of gained compound and above-mentioned formula (XV) compound subsequently,
Wherein A, R, X, l, Y and m as above define, and R
5Represent alkyl,
Wherein A, R, X, l, Y and m define as above,
Wherein A, R, X, l, Y, m and L definition are as above.
Preparation method (h) (R in formula (IV)
3When representing hydrogen):
Described method is: reduction-type (XIX) compound,
Wherein A, R, X, l, Y, m, n, R
1And R
2Definition as above.
Some compounds of above-mentioned formula (XII) are the compound described in the WO 2005/085216 among the preparation method (e), and can obtain according to for example following preparation method (i) to (k).
Preparation method (i)
Described method is: make the reaction of above-mentioned formula (III) compound and formula (XX) compound,
Wherein A, Y, m, n, R
1, R
2Define as above with Hal.
Preparation method (j)
Described method is: make formula (XXI) compound molecule intramolecular cyclization,
Wherein A, R, X, l, Y, m, R
1And R
2Definition as above.
Preparation method (k)
Described method is: make the reaction of formula (XXII) compound and hydroxy amine hydrochloric acid salt,
Wherein A, R, X, l, Y, m, R
1And R
2Definition as above.
Some compounds of above-mentioned preparation method (i) Chinese style (XX) are new compound, and can obtain by the preparation method who for example is similar to above-mentioned preparation method (a) Chinese style (II) compound.
The representative instance of formula (XX) compound comprises:
N-hydroxy-4-methyl benzene carboxylic imino-chlorine, 3-fluoro-N-hydroxy-4-methyl benzene carboxylic imino-chlorine, 3-chloro-N-hydroxy-4-methyl benzene carboxylic imino-chlorine, 3-bromo-N-hydroxy-4-methyl benzene carboxylic imino-chlorine, N-hydroxyl-3-iodo-4-methylbenzene carboxylic imino-chlorine and N-hydroxy-4-methyl-3-oil of mirbane carboxylic imino-chlorine.When two adjacent Y form a randomly substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XX) compound is N-hydroxy-4-methyl naphthalene-1-carboxylic imino-chlorine.
Above-mentioned preparation method (j) can be according to for example J.Chem.Soc.Chem.Commun., the 16th volume, 1983, the 873-875 pages or leaves; Chem Pharm.Bull., the 12nd volume, method described in 1964, the 1189-1192 pages or leaves is implemented.
The chemical compound lot of above-mentioned formula (XXI) is new compound and can obtains by following formula (XXIII) compound and oxyamine or its reactant salt:
Wherein A, R, X, l, Y, m, R
1And R
2Definition as above.
The chemical compound lot of above-mentioned formula (XXIII) is a new compound and can be according to for example ZhurnalOrganicheskoi Khimii, the 28th volume (No.3), and method described in the 518-526 page or leaf is synthetic.That is, the compound of formula (XXIII) can obtain by making the reaction of formula (XXIV) compound and formula (XXV) compound:
Wherein X, l and R define as above,
Wherein A, Y, m, n, R
1And R
2Definition as above.
The representative instance of above-mentioned formula (XXIV) compound comprises trifluoroacetophenone, 3 ', 5 '-two chloro-2,2, the 2-trifluoroacetophenone, 3 ', 4 '-two chloro-2,2, the 2-trifluoroacetophenone, 3 ', 4 ', 5 '-three chloro-2,2, the 2-trifluoroacetophenone, 3 '-fluoro-2,2, the 2-trifluoroacetophenone, 3 '-chloro-2,2, the 2-trifluoroacetophenone, 3 '-bromo-2,2, the 2-trifluoroacetophenone, 3 '-iodo-2,2, the 2-trifluoroacetophenone, 3 '-nitro-2,2, the 2-trifluoroacetophenone, 3 '-cyano group-2,2, the 2-trifluoroacetophenone, 3 '-(trifluoromethyl)-2,2,2-trifluoroacetophenone and 3 ', 5 '-two (trifluoromethyl)-2,2, the 2-trifluoroacetophenone.
The representative instance of above-mentioned formula (XXV) compound comprises 4-methyl acetophenone, 2-fluoro-4-methyl acetophenone, 2-chloro-4-methyl acetophenone, 2-bromo-4-methyl acetophenone, 2-iodo-4-methyl acetophenone, 4-methyl-2-nitro-acetophenone, 4-acetylbenzoic acid methyl esters, 4-ethanoyl-2-nitrobenzoic acid methyl esters, 4-ethanoyl-2-iodo-benzoic acid methyl esters and 4-ethanoyl benzonitrile.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XXV) compound is 1-(4-methylnaphthalene-1-yl) ethyl ketone.
The representative instance of above-mentioned formula (XXIII) compound comprises:
3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl) fourth-1-ketone, 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-1-(3-fluoro-4-aminomethyl phenyl)-3-hydroxyl fourth-1-ketone, 1-(3-chloro-4-aminomethyl phenyl)-3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-3-hydroxyl fourth-1-ketone, 1-(3-bromo-4-aminomethyl phenyl)-3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-3-hydroxyl fourth-1-ketone, 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-3-hydroxyl-1-(3-iodo-4-aminomethyl phenyl) fourth-1-ketone, 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-3-hydroxyl-1-(4-methyl-3-nitro phenyl) fourth-1-ketone and 4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl)-3-[3-(trifluoromethyl) phenyl] fourth-1-ketone.When two adjacent Y form a ring that randomly replaces for example during phenyl ring with the carbon atom that they connected, an example of formula (XXIII) compound is 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-3-hydroxyl-1-(4-methylnaphthalene-1-yl) fourth-1-ketone.
Formula (XXII) compound among the above-mentioned preparation method (k) is a new compound, and can react by above-mentioned formula (XXIII) compound and thionyl chloride and obtain.
The representative instance of formula (XXII) compound comprises: 4,4,4-three fluoro-1-(4-aminomethyl phenyl)-3-[3-(three fluoro-methyl) phenyl] but-2-ene-1-ketone, 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-1-(4-aminomethyl phenyl) but-2-ene-1-ketone, 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-1-(3-fluoro-4-aminomethyl phenyl) but-2-ene-1-ketone, 1-(3-chloro-4-aminomethyl phenyl)-3-(3, the 5-dichlorophenyl)-4,4,4-trifluoro but-2-ene-1-ketone, 1-(3-bromo-4-aminomethyl phenyl)-3-(3, the 5-dichlorophenyl)-4,4,4-trifluoro but-2-ene-1-ketone, 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-1-(3-iodo-4-aminomethyl phenyl) but-2-ene-1-ketone and 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-1-(4-methyl-3-nitro phenyl) but-2-ene-1-ketone.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XXII) compound is 3-(3, the 5-dichlorophenyl)-4,4,4-three fluoro-1-(4-methylnaphthalene-1-yl) but-2-ene-1-ketone.
Above-mentioned formula (XV) compound among the preparation method (f) is a known compound, and comprises for example ammoniacal liquor, methylamine, ethamine, Tri N-Propyl Amine, Isopropylamine, cyclopropylamine, allylamine, propargylamine, benzylamine, 1-pyridine-2-base methylamine, 1-pyridin-3-yl methylamine, 1-pyridin-4-yl methylamine.
Above-mentioned formula (XVI) compound among the preparation method (g) is (l) or (m) obtain by the following method.
Preparation method (l)
Described method is: make the reaction of above-mentioned formula (III) compound and formula (XXVI) compound,
Wherein A, Y, m, Hal and R
5Definition as above.
Preparation method (m)
Described method is: make (XXVII) compound molecule intramolecular cyclization,
Wherein A, R, X, l, Y, m and R
5Definition as above.
Some compounds of above-mentioned preparation method (l) Chinese style (XXVI) are new compound and can use the preparation method who for example is similar to above-mentioned preparation method (a) Chinese style (II) compound to obtain.
The representative instance of formula (XXVI) compound comprises: 4-[chlorine (oxyimino) methyl] methyl benzoate, 4-[chlorine (oxyimino) methyl]-the 2-methyl-toluate, 4-[chlorine (oxyimino) methyl]-the 2-fluorophenyl carbamate, 2-chloro-4-[chlorine (oxyimino) methyl] methyl benzoate, 2-bromo-4-[chlorine (oxyimino) methyl] methyl benzoate, 4-[chlorine (oxyimino) methyl]-2-iodo-benzoic acid methyl esters and 4-[chlorine (oxyimino) methyl]-2-nitrobenzoic acid methyl esters.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XXVI) compound be 4-[chlorine ((oxyimino) methyl] naphthalene-1-carboxylate methyl ester.
Above-mentioned preparation method (m) can implement according to the method that is similar to above-mentioned preparation method (j).The compound of above-mentioned formula (XXVII) can obtain by making following formula: compound and oxyamine or its reactant salt:
Wherein A, R, X, l, Y, m and R
5Definition as above.
The compound of above-mentioned formula (XXVIII) is new compound and can obtains by making the reaction of above-mentioned formula (XXIV) compound and following formula: compound:
Wherein A, Y, m and R
5Definition as above.
The compound of above-mentioned formula (XXIX) is a known compound; and for example comprise 4-acetylbenzoic acid methyl esters, 4-ethanoyl-2-methyl-toluate, 4-ethanoyl-2-fluorophenyl carbamate, 4-ethanoyl-2-chloro benzoic ether, 4-ethanoyl-2-methyl-bromobenzoate, 4-ethanoyl-2-iodo-benzoic acid methyl esters and 4-ethanoyl-2-nitrobenzoic acid methyl esters.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XXIX) compound is 4-ethanoyl naphthalene-1-carboxylate methyl ester.
Above-mentioned preparation method (h) Chinese style (XIX) compound comprises known compound and can be according to for example J.Org.Chem., 1999, the 64 volumes, and method is synthesized described in the 3171-3177 page or leaf.
The representative instance of above-mentioned preparation method (e) Chinese style (XII) compound comprises, for example 5-(3, the 5-dichlorophenyl)-3-(4-aminomethyl phenyl)-5-(trifluoromethyl)-4, the 5-dihydro-isoxazole, 5-(3, the 5-dichlorophenyl)-3-(3-fluoro-4-aminomethyl phenyl)-5-(trifluoromethyl)-4, the 5-dihydro-isoxazole, 3-(3-chloro-4-aminomethyl phenyl)-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4, the 5-dihydro-isoxazole, 3-(3-bromo-4-aminomethyl phenyl)-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4, the 5-dihydro-isoxazole, 5-(3, the 5-dichlorophenyl)-3-(3-iodo-4-aminomethyl phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole and 5-(3, the 5-dichlorophenyl)-3-(4-methyl-3-nitro phenyl)-5-(trifluoromethyl)-4, the 5-dihydro-isoxazole.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XII) compound is 5-(3, the 5-dichlorophenyl)-and 3-(4-methylnaphthalene-1-yl)-5-(trifluoromethyl)-4, the 5-dihydro-isoxazole.
The representative instance of preparation method (g) Chinese style (XVI) compound comprises:
4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] methyl benzoate, 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-methyl-toluate, 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] the 2-fluorophenyl carbamate, 2-chloro-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] methyl benzoate, 2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] methyl benzoate, 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-iodo-benzoic acid methyl esters, and 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-nitrobenzoic acid methyl esters.When two adjacent Y form a randomly substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XVI) compound is 4-[5-(3, the 5-dichlorophenyl)-and 5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] naphthalene-1-carboxylicesters.
The representative instance of preparation method (h) Chinese style (XIX) compound comprises:
4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzonitrile, 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-methyl benzonitrile, 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-fluorine benzonitrile, 2-chloro-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzonitrile, 2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzonitrile, 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-iodine benzonitrile, 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-nitrobenzonitrile, { 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } acetonitrile and { 2-bromo-4-[5-(3, the 5-dichlorophenyl)-and 5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } acetonitrile.When two adjacent Y form an optional substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XIX) compound is 4-[5-(3, the 5-dichlorophenyl)-and 5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] naphthalene-1-formonitrile HCN.
Formula V compound as raw material among the preparation method (b) is the known compound in the organic chemistry filed and comprises for example Acetyl Chloride 98Min., propionyl chloride, pivalyl chloride, acryloyl chloride, methyl-chloroformate, N, N-dimethyl carbamyl chloride, cyclopropyl carbonyl chloride, N, the N-dimethyl sulphide is for carbamyl chloride, Benzoyl chloride, nicotinoyl chlorine, diacetyl oxide, trifluoroacetic anhydride, methylsulfonyl chloride.
Preparation method's (b) reaction can be carried out in a kind of suitable diluent, described thinner for example comprises, aliphatic hydrocrbon (for example hexane, hexanaphthene, heptane), aromatic hydrocarbon (for example benzene,toluene,xylene, chlorobenzene), ether (for example diethyl ether, dibutyl ether, glycol dimethyl ether (DME), tetrahydrofuran (THF), dioxane), acid amides (for example dimethyl formamide (DMF), N,N-DIMETHYLACETAMIDE (DMA), N-Methyl pyrrolidone), nitrile (for example acetonitrile, propionitrile), methyl-sulphoxide (DMSO), water, or its mixture.
Preparation method's (b) reaction can use a kind of following alkali to carry out: alkali metal base comprises lithium hydride, sodium hydride, potassium hydride KH, lithium amide, sodium amide, diisopropylaminoethyl lithium, butyllithium, tert-butyl lithium, trimethyl silyl lithium, hexamethyl two silica-based Lithamides (lithiumhexamethyldisilazide), yellow soda ash, salt of wormwood, sodium acetate, potassium acetate, sodium methylate, sodium ethylate, potassium tert.-butoxide; And organic bases, comprise triethylamine, diisopropylethylamine, Tributylamine, N-methylmorpholine, N, accelerine, N, N-Diethyl Aniline, the 4-tertiary butyl-N, accelerine, pyridine, picoline, lutidine, diazabicyclo undecylene, diazabicyclo octane, imidazoles.
Preparation method's (b) reaction can be carried out in wide temperature range.Usually, this reaction can make an appointment with-78 ℃ to about 200 ℃, preferably carry out to about 150 ℃ temperature at about-10 ℃.This reaction is preferably carried out under promptly about 1000 mbar of normal pressure, but its can the pressure that improves promptly under the pressure more than 1000 mbar or the pressure that reduces promptly carry out under the pressure below 1000 mbar.Reaction times can be in 0.1-72 hour the scope, preferred 0.1-24 hour.
In implementing preparation method (b), for example 1 mole of formula (IV) compound can obtain the target compound of formula (I) with 1 to 3 mole of formula V compound, in reaction in the presence of a kind of alkali of 1 mole to 3 moles, in thinner (for example DMF).
Formula (VI) compound as raw material among the preparation method (c) is new compound and can obtains by for example following method (n) to (p).
Preparation method (n)
Described method is: make the reaction of following formula: compound and above-mentioned formula (III) compound,
Wherein A, Y, m, n, R
1, R
2, R
4Define as above with Hal.
Preparation method (o)
Described method is: make the reaction of following formula: compound and above-mentioned formula (VII) compound,
Wherein A, R, X, l, Y, m, n, R
1And R
2Definition as above.
Preparation method (p)
Described method is: make the reaction of above-mentioned formula (VIII) compound and following formula: compound,
R
4-NH
2??(XXXII)
R wherein
4Definition as above.
Above-mentioned preparation method (n) Chinese style (XXX) compound is that new compound and preparation method's that can be by being similar to above-mentioned preparation method (a) Chinese style (II) compound method obtains.
The representative instance of formula (XXX) compound for example comprises:
4-(formamido-methyl)-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-N-hydroxy-3-methyl benzene carboxylic imino-chlorine, 4-(acetylamino methyl)-3-fluoro-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-3-chloro-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-3-bromo-N-hydroxybenzene carboxylic imino-chlorine, 4-(acetylamino methyl)-N-hydroxyl-3-iodobenzene carboxylic imino-chlorine and 4-(acetylamino methyl)-N-hydroxyl-3-oil of mirbane carboxylic imino-chlorine.When two adjacent Y form a randomly substituted ring for example during phenyl ring with the carbon atom that they connected, an example of formula (XXX) compound is the 4-[(kharophen) methyl]-N-hydroxyl naphthalene-1-carboxylic imino-chlorine.
Formula (XXXI) compound among the above-mentioned preparation method (o) and R wherein
3For above-mentioned formula (IV) compound of hydrogen suitable.
Formula (XXXII) compound among the preparation method (p) is a known compound, and for example comprises, methane amide, ethanamide, propionic acid amide, 2,2,2-trifluoroacetamide, benzamide, urethanum and second sulphamide.
Preparation method's (c) reaction can be carried out under the condition identical with above-mentioned preparation method (b).
Some formulas (VIII) compound and above-mentioned formula (XIII) as raw material among the preparation method (d) are suitable with some compounds (XVIII).
The amide compound of above-mentioned formula (IX) is a known compound, and for example comprises, ethanamide, 2,2,2-trifluoroacetamide, 2,2,2-three fluoro-N-methylacetamides and pyrrolidin-2-one, piperidines-2-ketone, N-(pyridine-2-ylmethyl) ethanamide.
Preparation method's (d) reaction can be carried out under the condition identical with above-mentioned preparation method (b).
The compounds of this invention has effectively insect and acarid activity extremely extremely.Therefore, the compound by formula of the present invention (I) or formula (Ia) expression can be used as insecticide and miticide.They are used in particular in the agriculture field.The compounds of this invention also has suitable preventive and therapeutic effect to harmful insect and to the cultivated plant plant-less toxicity.In addition, The compounds of this invention can be used for preventing and treating various pests, comprise the insect of the parasitic insect of for example deleterious piercing-sucking mouthparts insect, chewing mouthparts insect and other plant, pest of stored grain and sanitary insect pest and veterinary applications, and can be used for to it control, particularly eradicate and go out and remove.Therefore, a kind of method of resisting harmful insect is also contained in the present invention.
The compounds of this invention is because of the toxicity that has good plant tolerance and favourable warm-blooded animal concurrently and have good environmental resistance; be suitable for protective plant and plant organ, raising gather productive rate, the quality of improving harvested material and control animal nuisance (animal pest), particularly insect, arachnid, worm, nematode and the mollusk that in protection, health field and the animal health field of agricultural, gardening, livestock industry, forest, gardens and leisure facilities, storage product and material, runs into.They can be preferably used as plant protection product.They have activity to common sensitivity and resistance species and to all or some etap.But the insect that the application of the invention compound and composition are resisted especially comprises:
Anoplura (Anoplura) (Phthiraptera), for example, Damalinia (Damalinia spp.), Haematopinus (Haematopinus spp.), Linognathus (Linognathus spp.), lice belong to (Pediculus spp.), Trichodectes (Trichodectes spp.).
Arachnida (Arachnida), for example, Acarus siro (Acarus siro), oranges and tangerines aceria (Aceria sheldoni), peronium Eriophyes (Aculops spp.), acupuncture Eriophyes (Aculusspp.), Amblyomma (Amblyomma spp.), Argas (Argas spp.), Boophilus (Boophilus spp.), short whisker Acarapis (Brevipalpus spp.), Bryobia praetiosa (Bryobiapraetiosa), Chorioptes (Chorioptes spp.), Dermanyssus gallinae (Dermanyssus gallinae), beginning Tetranychus (Eotetranychus spp.), goitre mite on the pears (Epitrimerus pyri), true Tetranychus (Eutetranychus spp.), Eriophyes (Eriophyes spp.), half tarsonemid mite belongs to (Hemitarsonemus spp.), Hyalomma (Hyalomma spp.), hard tick belongs to (Ixodesspp.), latrodectus mactans (Latrodectus mactans), Metatetranychus spp., the unguiculus mite belongs to (Oligonychus spp.), Ornithodoros (Ornithodoros spp.), Panonychus citri belongs to (Panonychus spp.), the tangerine rust mite (Phyllocoptruta oleivora) that rues, Polyphagotarsonemus latus Banks (Polyphagotarsonemus latus), Psoroptes (Psoroptes spp.), Rh (Rhipicephalus spp.), the root mite belongs to (Rhizoglyphus spp.), itch mite belongs to (Sarcoptes spp.), Middle East gold scorpion (Scorpio maurus), Stenotarsonemus spp., tarsonemid mite belongs to (Tarsonemus spp.), Tetranychus (Tetranychus spp.), Vasateslycopersici.
The Bivalva guiding principle, for example, Dreissena spp..
Lip foot order (Chilopoda), for example, DIWUGONG belongs to (Geophilus spp.), Scutigeraspp..
Coleoptera (Coleoptera), for example, acanthoscelides obtectus (Acanthoscelides obtectus), the beak rutelian belongs to (Adoretus spp.), willow firefly chrysomelid (Agelastica alni), click beetle belongs to (Agriotes spp.), the potato melolonthid (Amphimallon solstitialis), furniture death watch beetle (Anobium punctatum), longicorn beetle belongs to (Anoplophora spp.), flower resembles genus (Anthonomus spp.), Anthrenus (Anthrenus spp.), Ah gill cockchafer belongs to (Apogonia spp.), Atomaria spp., moth-eaten belong to (the Attagenus spp.) of fur, dislike bar bean weevil (Bruchidius obtectus), bean weevil belongs to (Bruchus spp.), tortoise resembles genus (Ceuthorhynchus spp.), Cleonus mendicus, wide chest Agriotes spp (Conoderus spp.), collar resembles genus (Cosmopolites spp.), the brown New Zealand rib wing melolonthid (Costelytra zealandica), Curculio (Curculio spp.), the latent beak of Yang Gan resembles (Cryptorhynchus lapathi), khapra beetle belongs to (Dermestes spp.), chrysomelid genus (Diabrotica spp.), epilachna genus (Epilachna spp.), Faustinus cubae, globose spider beetle (Gibbium psylloides), black different pawl sugarcane cockchafer (Heteronychus arator), Hylamorpha elegans, North America house longhorn beetle (Hylotrupes bajulus), alfalfa leaf resembles (Hypera postica), Hypothenemus spp., the big brown hock gill cockchafer of sugarcane (Lachnosterna consanguinea), colorado potato bug (Leptinotarsadecemlineata), rice root weevil (Lissorhoptrus oryzophilus), the tube beak resembles genus (Lixusspp.), moth-eaten belong to (the Lyctus spp.) of powder, pollen beetle (Meligethes aeneus), the west melolonthid in May (Melolontha melolontha), Migdolus spp., China ink day Bos (Monochamus spp.), Naupactus xanthographus, golden spider beetle (Niptushololeucus), coconut palm moth rhinoceros cockchafer (Oryctes rhinoceros), saw-toothed grain beetle (Oryzaephilussurinamensis), black grape ear image (Otiorrhynchus sulcatus), little blue and white cockchafer (Oxycetonia jucunda), horseradish ape chrysomelid (Phaedon cochleariae), food phyllobranchia cockchafer belongs to (Phyllophaga spp.), Japan popillia flavosellata fairmaire (Popillia japonica), Premnotrypes spp., rape golden head flea beetle (Psylliodes chrysocephala), Ptinus (Ptinus spp.), dark-coloured ladybug (Rhizobius ventralis), lesser grain borer (Rhizoperthadominica), grain weevil belongs to (Sitophilus spp.), point Rhynchophorus (Sphenophorusspp.), stem resembles genus (Sternechus spp.), Symphyletes spp., tenebrio molitor (Tenebriomolitor), Tribolium (Tribolium spp.), the spot khapra beetle belongs to (Trogoderma spp.), seed resembles genus (Tychius spp.), ridge tiger day Bos (Xylotrechus spp.), belong to (Zabrus spp.) apart from ground beetle; And Callosobruchus chinensis (Callosobruchus Chinensis), sitophilus zea-mais (Sitophilus zeamais), red flour beetle (Tribolium Castaneum), potato bug (Epilachna vigintioctomaculata), Agriotes subrittatus Motschulsky (Agriotesfuscicollis), Anomala rufocuprea, Leptinotarsa decemlineata, corn rootworm (Diabrotica spp.), Monochamus alternatus (Monochamus alternatus), rice water resembles (Lissorhoptrus oryzophilus), Lyctus bruneus and aulacophora femoralis (Aulacophora femoralis).
Collembola (Collembola), for example, arms Onychiurus arcticus (Onychiurus armatus).
Dermaptera (Dermaptera), for example, European earwig (Forficula auricularia).
Doubly sufficient order (Diplopoda), for example, Blaniulus guttulatus.
Diptera (Diptera), for example, Aedes (Aedes spp.), Anopheles (Anophelesspp.), garden march fly (Bibio hortulanus), calliphora erythrocephala (Calliphoraerythrocephala), Mediterranean Sea Ceratitis spp (Ceratitis capitata), Carysomyia (Chrysomyiaspp.), Callitroga (Cochliomyia spp.), Cordylobia anthropophaga, Culex (Culex spp.), Cuterebra (Cuterebra spp.), the big trypetid of olive (Dacus oleae), human botfly (Dermatobia hominis), Drosophila (Drosophila spp.), Fannia (Fanniaspp.), Gasterophilus (Gastrophilus spp.), Hylemyia (Hylemyia spp.), Hyppoboscaspp., Hypoderma (Hypoderma spp.), liriomyza bryoniae belongs to (Liriomyza spp.), Lucilia (Lucilia spp.), Musca (Musca spp.), Bemisia spp (Nezara spp.), Oestrus (Oestrus spp.), Oscinella frit (Oscinella frit), lamb's-quarters spring fly (Pegomyiahyoscyami), grass Hylemyia (Phorbia spp.), Genus Stomoxys (Stomoxys spp.), Gadfly (Tabanus spp.), Tannia spp., Europe daddy-longlegs (Tipula paludosa), Wohlfahrtia (Wohlfahrtia spp.); And housefly (Musca domestica), Aedes aegypti (Aedesaegypti), kind fly (Hylemia platura), northern house (Culex pipiens), Anopheles sinensis (Anopheles sinensis), Culex tritaeniorhynchus (Culex tritaeniorhychus) and trifolium liriomyza bryoniae (Liriomyza trifolii).
Gastropoda (Gastropoda), for example, Arion spp., Biomphalaria (Biomphalariaspp.), little Bulinus (Bulinus spp.), Deroceras spp., native snail belong to (Galba spp.), Lymnaea (Lymnaea spp.), Katayama (Oncomelania spp.), amber spiro spp (Succinea spp.).
Worm guiding principle (Helminth), for example, Ancylostoma duodenale (Ancylostomaduodenale), Sri Lanka hook worm (Ancylostoma ceylanicum), ancylostoma braziliense (Acylostoma braziliensis), Ancylostoma (Ancylostoma spp.), seemingly draw ascarid nematode (Ascaris lubricoides), Ascaris (Ascaris spp.), cloth Shandong, Malaysia nematode (Brugia malayi), cloth Shandong, Timor nematode (Brugia timori), Bunostomum (Bunostomum spp.), Chabertia belongs to (Chabertia spp.), branch testis fluke belongs to (Clonorchis spp.), Cooperia (Cooperia spp.), Dicrocoelium (Dicrocoelium spp.), dictyocaulus filaria (Dictyocaulus filaria), fish tapeworm (Diphyllobothrium latum), guinea worm (Dracunculusmedinensis), Echinococcus granulosus (Echinocoecus granulosus), Echinococcus multilocularis (Echinococcus multilocularis), pinworm (Enterobiusvermicularis), Faciola spp., blood Trichinella (Haemonchus spp.), Heterakis (Heterakis spp.), short and smallly nibble shell tapeworm (Hymenolepis nana), Metastrongylus apri belongs to (Hyostrongulus spp.), loa loa (Loa Loa), Nematodirus (Nematodirus spp.), oesophagostomum (Oesophagostomum spp.), Opisthorchis (Opisthorchis spp.), Onchocerca caecutiens (Onchocerca volvulus), this off-line Eimeria (Ostertagia spp.) difficult to understand, Paragonimus (Paragonimus spp.), Schistosomen spp., Fu Shi quasi-colubriformis (Strongyloides fuelleborni), strongyloides intestinalis (Strongyloides stercoralis), excrement Strongylus (Stronyloides spp.), taeniasis bovis (Taenia saginata), taeniasis suis (Taenia solium), trichina(Trichinella spiralis) (Trichinella spiralis), local hair shape nematode (Trichinella nativa), strain Bu Shi Trichinella spiralis (Trichinella britovi), south Trichinella spiralis (Trichinella nelsoni), Trichinellapseudopsiralis, trichostrongylus (Trichostrongulus spp.), Trichuris trichuria, wuchereria bancrofti (Wuchereria bancrofti).
In addition, also can prevent and treat protozoon, for example eimeria (Eimeria).
Heteroptera (Heteroptera), for example, squash bug (Anasa tristis), intend beautiful stinkbug and belong to (Antestiopsis spp.), the soil chinch bug belongs to (Blissus spp.), pretty fleahopper belongs to (Calocorisspp.), Campylomma livida, different back of the body chinch bug belongs to (Cavelerius spp.), Cimex (Cimex spp.), Creontiades dilutus, pepper coried (Dasynus piperis), Dichelops furcatus, the long excellent lace bug (Diconocoris hewetti) of Hou Shi, red cotton bug belongs to (Dysdercus spp.), the America stinkbug belongs to (Euschistus spp.), Eurygasterspp belongs to (Eurygasterspp.), Heliopeltis spp., Horcias nobilellus, Leptocorisa spp belongs to (Leptocorisa spp.), leaf beak coried (Leptoglossus phyllopus), lygus bug belongs to (Lygus spp.), sugarcane is deceived chinch bug (Macropes excavatus), Miridae (Miridae), Bemisia spp, Oebalus spp., Pentomidae, side butt stinkbug (Piesma quadrata), the wall stinkbug belongs to (Piezodorus spp.), cotton pseudo-spot leg fleahopper (Psallus seriatus), Pseudacysta persea, Rhodnius (Rhodnius spp.), Sahlbergella singularis (Sahlbergella singularis), black stinkbug belongs to (Scotinophora spp.), pear crown network pentatomidae (Stephanitis nashi), Tibraca spp., Triatoma (Triatoma spp.).
Homoptera (Homoptera), for example, no net long tube Aphis (Acyrthosipon spp.), Aeneolamia spp., grand arteries and veins Psylla spp (Agonoscena spp.), Aleurodes spp., sugarcane Aleyrodes (Aleurolobus barodensis), Aleurothrixus spp. Mango fruit leafhopper belongs to (Amrasca spp.), Anuraphis cardui, the kidney Aspidiotus belongs to (Aonidiella spp.), Soviet Union bloom aphid (Aphanostigma piri), Aphis (Aphis spp), grape leafhopper (Arboridiaapicalis), the roundlet armored scale belongs to (Aspidiella spp.), Aspidiotus belongs to (Aspidiotus spp.), Atanus spp., the eggplant ditch does not have net aphid (Aulacorthum solani), Bemisia spp., Lee's short-tail aphid (Brachycaudus helichrysii), Brachycolus spp., brevicoryne brassicae (Brevicorynebrassicae), little brown back rice plant hopper (Calligypona marginata), Carneocephala fulgida, cane powder angle aphid (Ceratovacuna lanigera), Cercopidae (Cercopidae), lecanium belongs to (Ceroplastes spp.), strawberry nail aphid (Chaetosiphon fragaefolii), sugarcane yellow snow armored scale (Chionaspis tegalensis), tea green leafhopper (Chlorita onukii), walnut blackspot aphid (Chromaphis juglandicola), dark brown Aspidiotus (Chrysomphalus ficus), corn leafhopper (Cicadulina mbila), Coccomytilus halli, soft a red-spotted lizard belongs to (Coccus spp.), the tea Fischer conceals knurl aphid (Cryptomyzus ribis), Dalbulus spp., Dialeurodes spp., Diaphorina spp., white back of the body armored scale belongs to (Diaspis spp.), Doralis spp., carry out giant coccid and belong to (Drosicha spp.), west rounded tail Aphis (Dysaphis spp.), the ash mealybug belongs to (Dysmicoccusspp.), Empoasca flavescens (Empoasca spp.), woolly aphid belongs to (Eriosoma spp.), Erythroneura spp., Euscelis bilobatus, coffee ground mealybug (Geococcus coffeae), phony disease of peach poison leafhopper (Homalodisca coagulata), mealy plum aphid (Hyalopterusarundinis), icerya purchasi belongs to (Icerya spp.), sheet angle leafhopper belongs to (Idiocerus spp.), flat beak leafhopper belongs to (Idioscopus spp.), small brown rice planthopper (Laodelphax striatellus), Lecaniumspp., lepidosaphes shimer (Lepidosaphes spp.), radish aphid (Lipaphis erysimi), long tube Aphis (Macrosiphum spp.), Mahanarva fimbriolata, kaoliang aphid (Melanaphis sacchari), Metcalfiella spp., wheat does not have net aphid (Metopolophiumdirhodum), the black flat wing spot of edge aphid (Monellia costalis), Monelliopsis pecanis, tumor aphid genus (Myzus spp.), lettuce is patched up Macrosiphus spp (Nasonovia ribisnigri), rice green leafhopper belongs to (Nephotettix spp.), brown paddy plant hopper (Nilaparvata lugens), Oncometopiaspp., Orthezia praelonga, red bayberry edge aleyrodid (Parabemisia myricae), Paratriozaspp., the sheet armored scale belongs to (Parlatoria spp.), the goitre woolly aphid belongs to (Pemphigus spp.), corn plant hopper (Peregrinus maidis), continuous mealybug belongs to (Phenacoccus spp.), Yang Ping wing woolly aphid (Phloeomyzus passerinii), phorodon aphid (Phorodon humuli), Phylloxeraspp., brown point of sago cycas and armored scale (Pinnaspis aspidistrae), stern line mealybug belongs to (Planococcusspp.), the former giant coccid of pyriform (Protopulvinaria pyriformis), white mulberry scale (Pseudaulacaspis pentagona), mealybug belongs to (Pseudococcus spp.), Psylla spp (Psylla spp.), tiny golden wasp belongs to (Pteromalus spp.), Pyrilla spp., the large bamboo hat with a conical crown and broad brim Aspidiotus belongs to (Quadraspidiotus spp.), Quesada gigas, flat thorn mealybug belongs to (Rastrococcusspp.), Rhopalosiphum (Rhopalosiphum spp.), black bourch belongs to (Saissetia spp.), Scaphoides titanus, green bugs (Schizaphis graminum), sago cycas thorn Aspidiotus (Selenaspidus articulatus), long clypeus plant hopper belongs to (Sogata spp.), white backed planthopper (Sogatella furcifera), Sogatodes spp., Stictocephala festina, Tenalapharamalayensis, Tinocallis caryaefoliae, wide chest froghopper belongs to (Tomaspis spp.), sound Aphis (Toxoptera spp.), greenhouse whitefly (Trialeurodes vaporariorum), individual Psylla spp (Trioza spp.), jassids belongs to (Typhlocyba spp.), the point armored scale belongs to (Unaspisspp.), Viteus vitifolii.
Hymenoptera (Hymenoptera), for example, pine sawfoy belongs to (Diprion spp.), real tenthredinidae (Hoplocampa spp.), the hair ant belongs to (Lasius spp.), MonomoriumMayr (Monomoriumpharaonis), Vespa (Vespa spp.).
Isopoda (Isopoda), for example, pillworm (Armadillidium vulgare), comb beach louse (Oniscus asellus), ball pillworm (Porcellio scaber).
Isoptera (Isoptera), for example, Reticulitermes (Reticulitermes spp.), odontotermes (Odontotermes spp.); And eastern subterranean termite (Reticulitermes speratus) and Coptotermes formosanus Shtrari (Coptotermes formosanus).
Lepidopteran (Lepidoptera), for example, Sang Jian Autographa spp (Acronicta major), tired noctuid (Aedia leucomelas), Agrotis (Agrotis spp.), cotton leaf ripple noctuid (Alabama argillacea), do very Noctua (Anticarsia spp.), Barathrabrassicae, cotton lyonetid (Bucculatrix thurberiella), loose looper (Bupalus piniarius), the yellow volume of flax moth (Cacoecia podana), Capua reticulana, codling moth (Carpocapsa pomonella), winter geometrid moth (Cheimatobia brumata), straw borer spp (Chilo spp.), spruce bunworm (Choristoneura fumiferana), grape codling moth (Clysia ambiguella) (Clysia ambiguella), Cnaphalocerus spp., earias insulana (Eariasinsulana), Anagasta kuehniella (Ephestia kuehniella), pornography and drug moth (Euproctischrysorrhoea), cutworm belongs to (Euxoa spp.), the dirty Noctua (Feltia spp.) of cutting, greater wax moth (Galleria mellonella), Helicoverpa spp., Heliothis (Heliothisspp.), brownly knit moth (Hofmannophila pseudospretella), tea long paper moth (Homonamagnanima), apple ermine moth (Hyponomeuta padella), greedy Noctua (Laphygmaspp.), the thin moth of apple (Lithocolletis blancardella), green fruit winter noctuid (Lithophaneantennata), the grand in vain cutworm (Loxagrotis albicosta) of beans, Euproctis (Lymantriaspp.), malacosoma neustria (Malacosoma neustria), lopper worm (Mamestrabrassicae), rice hair shin noctuid (Mocis repanda), mythimna separata (Mythimma separata), Oria spp., Oulema oryzae (Oulema oryzae), small noctuid (Panolis flammea), Pectinophora gossypiella (Pectinophora gossypiella), tangerine lyonetid (Phyllocnistis citrella), Pieris spp (Pieris spp.), diamond-back moth (Plutella xylostella), prodenia litura belongs to (Prodeniaspp.), Pseudaletia spp., soybean noctuid (Pseudoplusia includens), Pyrausta nubilalis (Hubern). (Pyrausta nubilalis), Spodoptera (Spodoptera spp.), Thermesiagemmatalis, bag rain moth (Tinea pellionella), curtain rain moth (Tineola bisselliella), the green volume of oak moth (Tortrix viridana), powder Noctua (Trichoplusia spp.); And gypsymoth (Lymantria dispar), malacosoma neustria (Malacosoma neustria), cabbage caterpillar (Pieris rapae), prodenia litura (Spodoptera litura), lopper worm (Mamestrabrassicae), striped rice borer (Chilo suppressalis), Pyrausta nubilalis (Hubern). (Pyrausta nubilalis), Ephestia cautella, apple volume moth (Adoxophyes orana), codling moth (Carpocapsapomonella), the blue or green cutworm (Agrotis fucosa) of swallow, greater wax moth (Galleria mellonella), small cabbage moth (Plutella maculipennis), Heliothis virescens (Heliothis virescens) and tangerine lyonetid (Phyllocnistis citrella).
Orthoptera (Orthoptera), for example, tame Xi (Acheta domesticus), oriental cockroach (Blatta orientalis), Gryllotalpa spp (Gryllotalpa spp.), leucophaea maderae (Leucophaea maderae), migratory locusts belong to (Locusta spp.), black locust belongs to (Melanoplusspp.), desert locust (Schistocerca gregaria); And blatta germanica (Blattella germanica), periplaneta americana (Periplaneta americana), African mole cricket (Gryllotalpa africana) and African migratory locust (Locusta migratoria migratoriaodes).
Siphonaptera (Siphonaptera), for example, Ceratophyllus (Ceratophyllus spp.), Xanthopsyllacheopis (Xenopsylla cheopis).
Comprehensive order (Symphyla), for example, Scutigerella immaculata.
Thysanoptera (Thysanoptera), for example, rice thrips (Baliothrips biformis), Enneothrips flavens, flower thrips belong to (Frankliniella spp.), net Thrips (Heliothripsspp.), greenhouse bar hedge thrips (Hercinothrips femoralis), card Thrips (Kakothripsspp.), grape thrips (Rhipiphorothrips cruentatus), hard Thrips (Scirtothripsspp.), Taeniothrips cardamoni, Thrips (Thrips spp.); And palm thrips (Thrips palmi) and Frankliniella occidentalis (Frankliniella occidentalis).
Hemiptera, for example rice green leafhopper (Nephotettix cincticeps), brown paddy plant hopper (Nilaparvatalugens), Kang Shi mealybug (Pseudococcus comstocki), unaspis shield kuwana (Unaspisyanonensis), black peach aphid (Myzus persicas), apple aphid (Aphis pomi), cotten aphid (Aphis gossypii), turnip aphid (Rhopalosiphum pseudobrassicas), pear crown network pentatomidae (Stephanitis nashi), Nazara spp., Trialeurodes vaporariorum Westwood (Trialeurodesvaporariorm) and Pshylla spp.;
Thysanura (Thysanura), for example, silverfish (Lepisma saccharina).
Plant nematode comprises, for example, eel Turbatrix (Anguina spp.), Aphelenchoides (Aphelenchoides spp.), thorn Turbatrix (Belonoaimus spp.), umbrella Aphelenchoides (Bursaphelenchus spp.), fuller's teasel Ditylenchus dipsaci (Ditylenchus dipsaci), ball Heterodera (Globodera spp.), spiral-line Eimeria (Heliocotylenchus spp.), Heterodera (Heterodera spp.), minute hand Turbatrix (Longidorus spp.), Meloidogyne (Meloidogyne spp.), similar similes thorne (Radopholus similis), shallow bid revolves Turbatrix (Rotylenchus spp.), burr Turbatrix (Trichodorus spp.), downgrade Turbatrix (Tylenchorhynchus spp.), pulvinulus sword Turbatrix (Tylenchulus spp.), the nematode (Tylenchulus semipenetrans) of partly puncturing, Xiphinema (Xiphinema spp.); And Meloidogyne incognita (Meloidogyne incognita), Bursaphelenchus lignicolusMamiya et Kiyohara, aphelenchoides besseyi (Aphelenchoides besseyi) and soybean Cyst nematode (Heterodera glycines) and Pratylenchidae genus (Pratylenchus spp.).
Acarid for example comprises that carmine spider mite (Tetranychus cinnabarinus), Tetranychus urticae (Tetranychus urticae), citrus red mite (crm) (Panonychus citri), Aculopspelekassi and instep line belong to (Tarsonemus spp.).
If it is suitable, The compounds of this invention also can finite concentration or rate of application as weedicide, safener, growth regulator or improve the medicament of plant characteristic, or as microbicide, for example mycocide, antimycotic agent, bactericide, virucide (comprising the medicament of resist viroid) or as the medicament of resisting MLO (mycoplasma-like organism(MLO)) and RLO (rickettsia-like organism).If suitable, they also can be used as the intermediate or the precursor of synthetic other active compounds.
In veterinary applications, new compound of the present invention can be used to resist multiple pest parasite (vermin and endoparasite), for example insect and worm effectively.
The example of described zooparasite comprises following insect:
Insect comprises for example Gasterophilus (Gastrophilus spp.), Genus Stomoxys (Stomoxys spp.), Trichodectes (Trichodectes spp.), Rhodnius (Rhodnius spp.), ctenocephalides canis (Ctenocephalides canis), Cimex lecturius, ctenocephalides felis (Ctenocephalidesfelis) and lucilia cuprina (Lucilia cuprina);
Acarid comprises that for example Ornithodoros (Ornithodoros spp.), hard tick belong to and Boophilus (Boophilus spp.) (now being called Rh (Rhipicephalus spp.)).
As mentioned before, in veterinary applications, promptly in the veterinary field, active compound of the present invention is to zooparasite---particularly vermin or endoparasite---has activity.The term endoparasite comprises particularly worm, for example tapeworm, nematode or fluke; And protozoon, for example coccidia.Vermin usually and be preferably arthropods, particularly insect, as fly (terebra and lick suction), tachinid larva, sucking louse, food hair lice, flea etc.; Or acarid, tick for example, as hard tick or soft ticks, or acarian, for example itch mite, harvest mite, bird mite etc.
These parasites comprise:
Anoplura (Anoplurida), for example, Haematopinus (Haematopinus spp.), Linognathus (Linognathus spp.), lice belong to (Pediculus spp.), Phtirus spp., the pipe lice belongs to (Solenopotes spp.); Specific examples has: sour jujube jaw lice (Linognathus setosus), Linognathus vituli (Linognathus vituli), sheep jaw lice (Linognathus ovillus), Linognathusoviformis, foot jaw lice (Linognathus pedalis), goat jaw lice (Linognathusstenopsis), giant's haematopinus asina (Haematopinus asini macrocephalus), haematopinus eurysternus (Haematopinus eurysternus), haematopinus suis (Haematopinus suis), head louse (Pediculus humanus capitis), body louse (Pediculus humanus corporis), grape phylloxera (Phylloera vastatrix), crab louse (Phthirus pubis), solenoptes capillatus (Solenopotes capillatus);
Mallophaga (Mallophagida) and Amblycera (suborder Amblycerina) and thin angle suborder (suborder Ischnocerina), for example, hair Trichodectes (Trimenoponspp.), Menopon (Menopon spp.), huge Trichodectes (Trinoton spp.), Bovicola (Bovicola spp.), Werneckiella spp., Lepikentron spp., Damalinia (Damalina spp.), Trichodectes (Trichodectes spp.), Felicola (Felicolaspp.); Specific examples has: ox hair lice (Bovicola bovis), wool lice (Bovicola ovis), Bovicola limbata, Damalinia bovis (Damalina bovis), dog hair lice (Trichodectescanis), cat poultry louse (Felicola subrostratus), goathair lice (Bovicola caprae), Lepikentron ovis, sting lice (Werneckiella equi);
Diptera and Nemocera (suborder Nematocerina) and Brachycera (suborder Brachycerina), for example, Aedes (Aedes spp.), Anopheles (Anophelesspp.), Culex (Culex spp.), Simulium (Simulium spp.), Eusimulium (Eusimuliumspp.), owl midge (Phlebotomus spp.), Lutzomyia (Lutzomyia spp.), Bitting midge (Culicoides spp.), Chrysops (Chrysops spp.), Odogmia (Odagmiaspp.), Wilhelmia spp., Hybomitra (Hybomitra spp.), Atylotus (Atylotusspp.), Gadfly (Tabanus spp.), Chrysozona (Haematopota spp.), Philipomyiaspp., honeybee Hippobosca (Braula spp.), Musca (Musca spp.), Hydrotaea (Hydrotaeaspp.), Genus Stomoxys (Stomoxys spp.), Haematobia (Haematobia spp.), fly does not belong to (Morellia spp.), Fannia (Fannia spp.), Glossina (Glossina spp.), Calliphora (Calliphora spp.), Lucilia (Lucilia spp.), Carysomyia (Chrysomyiaspp.), Wohlfahrtia (Wohlfahrtia spp.), Sarcophaga (Sarcophaga spp.), Oestrus (Oestrus spp.), Hypoderma (Hypoderma spp.), Gasterophilus (Gasterophilusspp.), Hippobosca (Hippobosca spp.), Lipoptena (Lipoptena spp.), Melophagus (Melophagus spp.), Rhinoestrus (Rhinoestrus spp.), big uranotaenia (Tipulaspp.); Specific examples has: Aedes aegypti (Aedes aegypti), Aedes albopictus (Aedesalbopictus), aedes taeniorhynchus (Aedes taeniorhynchus), anopheles costalis (Anophelesgambiae), anopheles maculipennis (Anopheles maculipennis), calliphora erythrocephala (Calliphoraerythrocephala), great number fiber crops horsefly (Chrysozona pluvialis), five band culex pipiens pollens (Culexquinquefasciatus), northern house (Culex pipiens), ring beak culex (Culex tarsalis), Fannia canicularis (Fannia canicularis), flesh fly (Sarcophaga carnaria), tatukira (Stomoxys calcitrans), the Europe daddy-longlegs, lucilia cuprina, lucilia sericata (Lucilia sericata), Simulium reptans (Simulium reptans), quiet food sand fly (Phlebotomus papatasi), phlebotomus lognipes (Phlebotomus longipalpis), magnificent short buffalo gnat (Odagmia ornata), Wilhelmiaequina, reddish tone is detested buffalo gnat (Boophthora erythrocephala), many horseflys (Tabanusbromius), noctuid horsefly (Tabanus spodopterus), tabanus atratus (Tabanus atratus), Tabanus sudeticus, Gooch knurl horsefly (Hybomitra ciurea), chrysops cecutiens (Chrysopscaecutiens), chrysops relictus (Chrysops relictus), great number fiber crops horsefly (Haematopotapluvialis), Haematopota italica, face fly (Musca autumnalis), housefly, Haematobia irritans irritans, Haematobia irritans exigua, thorn Haematobia irritans (Haematobia stimulans), Hydrotaea irritans, hickie tooth thigh fly (Hydrotaeaalbipuncta), Chrysomya chloropyga, maggot disease gold fly (Chrysomya bezziana), Oestrus ovis (Oestrus ovis), bomb fly (Hypoderma bovis), heel fly (Hypodermalineatum), Przhevalskiana silenus, people torsalo (Dermatobia hominis), sheep tick (Melophagus ovinus), Lipoptena capreoli, Lipoptena cervi, Hippobosca variegata, horse louse fly (Hippobosca equina), Gasterophilus intestinalis (Gasterophilus intestinalis), Gasterophilus haemorrhoidalis (Gasterophilus haemorroidalis), naked joint stomach fly (Gasterophilus inermis), gasterophilus nasalis (Gasterophilus nasalis), black angle stomach fly (Gasterophilus nigricornis), gastrophilus pecorum (Gasterophiluspecorum), honeybee hippoboscid (Braula coeca);
Siphonaptera (Siphonapterida), for example, flea belongs to (Pulex spp.), Ctenocephalus (Ctenocephalides spp.), Dermatophilus (Tunga spp.), objective flea genus (Xenopsyllaspp.), Ceratophyllus (Ceratophyllus spp.); Specific examples has: ctenocephalides canis (Ctenocephalides canis), ctenocephalides felis, Pulex irritans (Pulex irritans), chigo (Tunga penetrans), Xanthopsyllacheopis;
Heteroptera (Heteropterida), for example, Cimex (Cimex spp.), Triatoma (Triatoma spp.), Rhodnius (Rhodnius spp.), Triatoma (Panstrongylusspp.);
Blattodea (Blattarida), for example, oriental cockroach (Blatta orientalis), periplaneta americana (Periplaneta americana), blatta germanica (Blattela germanica), Supella (Supella spp.) (for example Suppella longipalpa);
Acarian (Acari or Acarina) subclass and back valve order (Metastigmate) and Mesostigmata (Mesostigmata), for example, Argas, Ornithodoros (Ornithodorus spp.), residual beak tick belongs to (Otobius spp.), hard tick belongs to, Amblyomma, Rh (Boophilus) (Rhipicephalus (Boophilus) spp.), Dermacentor (Dermacentor spp.), Haemophysalis spp., Hyalomma (Hyalomma spp.), Dermanyssus (Dermanyssusspp.), Rh (belonging to originally of many hosts tick), Ornithonyssus (Ornithonyssus spp.), Pneumonyssus (Pneumonyssus spp.), sting sharp mite and belong to (Raillietia spp.), Pneumonyssusspp., chest thorn mite belongs to (Sternostoma spp.), Vespacarus (Varroa spp.), Acarapisspp.; Specific examples has: adobe tick (Argas persicus), stick up edge sharp-edged tick (Argasreflexus), tampan tick (Ornithodorus moubata), Otobius megnini, small fan head tick (boophilus microplus) (Rhipicephalus (Boophilus) microplus), colour killing fan head tick (boophilus decoloratus) (Rhipicephalus (Boophilus) decoloratus), tool ring fan head tick (Boophilus annulatus) (Rhipicephalus (Boophilus) annulatus), square fan head tick (square ox tick is arranged) (Rhipicephalus (Boophilus) calceratus) is arranged, hyalomma anatolicum (Hyalomma anatolicum), Hyalomma aegypticum (Hyalomma aegypticum), edge glass eye tick (Hyalomma marginatum), Hyalomma transiens, rhipicephalus evertsi (Rhipicephalus evertsi), castor bean tick (Ixodes ricinus), the hard tick of hexagonal (Ixodeshexagonus), the hard tick in open country (Ixodes canisuga), ixodes pilosus (Ixodes pilosus), ixodes rubicundus (Ixodes rubicundus), ixodes scapularis (Ixodes scapularis), ixodes holocyclus (Ixodes holocyclus), haemaphysalis conicinna (Haemaphysalis concinna), Haemaphysalis punctata (Haemaphysalis punctata), Haemaphysalis cinnabarina, Haemaphysalis otophila, haemaphysalis leachi (Haemaphysalis leachi), haemaphysalis longicornis (Haemaphysalis longicorni), dermacentor marginatus (Dermacentor marginatus), dermacentor reticulatus (Dermacentor reticulatus), Dermacentor pictus, Dermacentoralbipictus, Dermacentor andersoni (Dermacentor andersoni), Dermacentor variabilis (Dermacentorvariabilis), Mauritius's glass eye tick (Hyalomma mauritanicum), brown dog tick (Rhipicephalus sanguineus), scrotiform fan head tick (Rhipicephalus bursa), rhipicephalus appendiculatus (Rhipicephalus appendiculatus), rhinpicephalus capensis (Rhipicephalus capensis), scheme blue fan head tick (Rhipicephalus turanicus), Rhipicephalus zambeziensis, lone star tick (Amblyomma americanum), illuminated flower tick (Amblyomma variegatum, spot flower tick (Amblyommamaculatum) is arranged, Hebrew spends tick (Amblyomma hebraeum), card prolongs colored tick (Amblyomma cajennense), Dermanyssus gallinae (Dermanyssus gallinae), capsule fowl thorn mite (Ornithonyssus bursa), northern fowl mite (Ornithonyssus sylviarum), varoa mite (Varroa jacobsoni);
Axle Acarina (Actinedida) (preceding valve suborder (Prostigmata)) and flour mite order (Acaridida) (Astigmata (Astigmata)), for example, honeybee shield mite belongs to (Acarapisspp.), Cheyletiella (Cheyletiella spp.), Ornithocheyletia (Ornithocheyletia spp.), Myobia (Myobia spp.), Psorergates (Psorergates spp.), Demodex (Demodexspp.), Trombidium (Trombicula spp.), Listrophorus spp., Tyroglyphus (Acarusspp.), Tyrophagus (Tyrophagus spp.), have a liking for wooden mite and belong to (Caloglyphus spp.), mite belongs to (Hypodectes spp.) under the neck, the wing mite belongs to (Pterolichus spp.), Psoroptes (Psoroptes spp.), Chorioptes (Chorioptes spp.), the ear itch mite belongs to (Otodectes spp.), itch mite belongs to (Sarcoptes spp.), Notoedres (Notoedres spp.), the lump mite belongs to (Knemidocoptes spp.), Cytodites (Cytodites spp.), Laminosioptes (Laminosioptes spp.); Specific examples has: Ya Shi Ji chela mite (Cheyletiella yasguri), cheyletiella blakei (Cheyletiella blakei), dog demodicid mite (Demodex canis), ox demodicid mite (Demodex bovis), sheep demodicid mite (Demodex ovis), goat demodicid mite (Demodex caprae), horse demodicid mite (Demodex equi), Demodex caballi, pig demodicid mite (Demodex suis), Neotrombicula autumnalis, Neotrombiculadesaleri;
Xerothermobia, bete rouge (Trombiculaakamushi), dog ear mite (Otodectes cynotis), cat scab mite (Notoedres cati), sarcoptes canis (Sarcoptis canis), Sarcoptes bovis (Sarcoptes bovis), sheep itch mite (Sarcoptesovis), the goat itch mite (Sarcoptes rupicaprae (=S.caprae)), sarcoptes equi (Sarcoptesequi), Sarcoptes suis (Sarcoptes suis), sheep scabies mite (Psoroptes ovis), rabbit scabies mite (Psoroptes cuniculi), horse scabies mite (Psoroptes equi), psoroptes bovis (Chorioptesbovis), Psoergates ovis, Pneumonyssoidic Mange, dog Bi Jie Insect (Pneumonyssoides caninum), Wu Shi honeybee tarsonemid mite (Acarapis woodi).
Active compound of the present invention also is suitable for preventing and treating arthropods, worm and the protozoon of invasion and attack animal.Preferred control arthropods.Especially preferably prevent and treat insect.Comparably, especially preferably prevent and treat mite.
Can handle to prevent and treat parasitic animal and comprise bird, insect and particularly Mammals.Animal comprises agriculture domestic animal, for example ox, sheep, goat, horse, pig, donkey, camel, buffalo, rabbit, tame chicken, furbearer, turkey, duck, goose, breed fish, honeybee.Animal also comprises domestic animal in addition---being also referred to as companion animals---for example dog, cat, ferret, cage bird, aquarium fish, Reptilia, and alleged laboratory animal, for example hamster, cavy, rat and mouse.
By preventing and treating these arthropodss, worm and/or protozoon, be intended to reduce the death of host animal, and improve its (meat, milk, hair, skin, egg, honey etc.) productivity and healthy state, but so that the application of the invention active compound and make animal rearing more economical and easier.
For example, wish prevention or interruption parasite picked-up host's blood (working as where applicable).In addition, the control parasite can help to prevent the propagation of infectious agent.
The term " control " relevant with veterinary applications used herein means active compound can make the sickness rate of each parasite in infecting described parasitic animal be reduced to harmless level effectively.More specifically, " control " used herein mean active compound and can effectively kill each parasite, suppress its growth or suppress its breeding.
When active compound of the present invention is used as sterilant, can be made into the conventional formulation form.Described dosage form for example comprises, solution, emulsion, wettable powder, water dispersible granules, suspension agent, pulvis, foaming agent, paste, tablet, granule, aerosol, natural and synthetics, microcapsule, coating agent for seed, the preparation (combustion unit comprise for example fumigate and sootiness tube, jar and coil pipe (fumigationand smoking cartridges, cans and coils)) that uses with combustion unit (burning device) and the cold mist agent of UVL[, thermal fog] through the active compound dipping.
These preparations can prepare according to currently known methods.For example, they can be by mixing active compound with weighting agent, promptly mix, and the optional tensio-active agent that uses, i.e. emulsifying agent and/or dispersion agent and/or whipping agent and make with liquid diluent or carrier, liquefied gas diluent or carrier, solid diluent or carrier.These preparations are preparation in advance or directly preparation before using or in the application in suitable device.
Be suitable for use as the material of---for example some technical feature and/or particular organisms performance---for being suitable for giving compound and composition itself and/or preparation therefrom (for example spray liquor, seed dressing) specified property of auxiliary agent.Typical proper auxiliary agent has: weighting agent, solvent or thinner and carrier.
Suitable weighting agent has for example water, polarity and nonpolar organic chemistry liquid, organic chemistry liquid as following kind: aromatic hydrocarbon and non-aromatic hydrocarbon (for example paraffin, alkylbenzene, alkylnaphthalene, chlorobenzene), pure and mild polyvalent alcohol are (if suitable, it also can be substituted, etherificate and/or esterification), ketone (for example acetone, pimelinketone), ester (comprising fat and oil) and (gathering) ether, unsubstituted and substituted amine, acid amides, lactan (for example N-alkyl pyrrolidone) and lactone, sulfone and sulfoxide (for example methyl-sulphoxide).
If used weighting agent is a water, for example also can use organic solvent as solubility promoter.
Suitable solid carrier for example has, ammonium salt and natural mineral such as kaolin, clay, talcum, chalk, quartz, attapulgite, montmorillonite or the diatomite pulverized, and synthetic mineral of pulverizing such as finely divided silicon-dioxide, aluminum oxide and silicate; The solid carrier that is applicable to granule has: for example pulverize and the fractionated natural rock, as calcite, marble, float stone, sepiolite and rhombspar; And the inorganic and organic powder particles of synthetic; Reach for example particle of paper, sawdust, coconut husk, corn cob and tobacco stem of organism; Examples of suitable emulsifiers and/or whipping agent have: for example nonionic and anionic emulsifier, as polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether, as alkylaryl polyglycol ether, alkylsulfonate, alkyl-sulphate, arylsulphonate, and protein hydrolyzate; Suitable dispersion agent has nonionic and/or ionic species, for example the material of following classification: alcohol-POE-and/or alcohol-POP ether, acid and/or POP-POE ester, alkylaryl and/or POP-POE ether, fat-and/or POP-POE adducts, POE-and/or POP-polyol derivative, POE-and/or POP-Sorbitol Powder or-sucrose adducts, alkyl or aryl sulfuric ester, alkyl or aryl sulphonate, and the alkyl or aryl phosphoric acid ester, perhaps corresponding PO-ether adducts.Suitable in addition oligopolymer or polymkeric substance be, for example by vinyl monomer, by vinylformic acid, by oligopolymer or polymkeric substance independent or that obtain with for example (gathering) EO that alcohol or (gathering) amine combines and/or PO.Also can use the adducts of Mierocrystalline cellulose, aromatics and/or the aliphatic sulfonic acid of xylogen and sulfonic acid thereof, unmodified and modification and they and formaldehyde.
Liquid diluent, solvent or carrier for example comprise, aromatic hydrocarbon (for example dimethylbenzene, toluene, alkylnaphthalene), chlorinated aromatics or chlorination aliphatic hydrocrbon (for example chlorobenzene, vinylchlorid, methylene dichloride), aliphatic hydrocrbon [for example hexanaphthene or paraffin (for example mineral oil fractions or vegetables oil)], alcohol (for example butanols, ethylene glycol and their ether or ester), ketone (for example acetone, methylethylketone, methyl iso-butyl ketone (MIBK), pimelinketone), intensive polar solvent (for example dimethyl formamide, methyl-sulphoxide); And water.
The liquefied gas diluent or carrier is included in the material that exists with gas under normal temperature and the normal pressure, and comprises for example aerosol spray, as furans, propane, nitrogen, carbonic acid gas and halohydrocarbon.
Suitable thinner comprises the natural mineral of for example pulverizing (for example kaolin, clay, talcum, chalk, quartz, attapulgite, montmorillonite or diatomite) and the synthetic mineral (for example finely divided silicic acid, aluminum oxide, silicate) of pulverizing.
The solid carrier that is applicable to granule for example comprises, pulverize and fractionated rock (for example calcite, marble, float stone, sepiolite, rhombspar), synthetic is inorganic or organic powder particles, and the fine particle of organism (for example sawdust, coconut husk, corn cob, tobacco stem).
Emulsifying agent and/or whipping agent for example comprise, for example nonionic or anionic emulsifier [for example polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether (for example alkylaryl polyglycol ether), alkylsulfonate, alkyl-sulphate, arylsulphonate], and albumin hydrolysate.
Dispersion agent for example comprises, lignin sulfite waste lye and methylcellulose gum.
Also can use tackiness agent in the preparation (pulvis, granule, emulsion), described tackiness agent for example comprises, carboxymethyl cellulose and natural or synthetic polymer (for example Sudan Gum-arabic, polyvinyl alcohol, polyvinyl acetate).
Can use tinting material, and it for example comprises, mineral dye (for example ferric oxide, titanium oxide, Prussian blue), organic dye (for example alizarine dyestuff, azoic dyestuff or metal phthalocyanine dyestuff), and trace element (for example molysite, manganese salt, boron salt, mantoquita, cobalt salt, molybdenum salt and zinc salt).
Other available auxiliary agents have spices, optional mineral oil or vegetables oil, wax and nutrient substance (comprising trace nutrient) through modification, for example molysite, manganese salt, boron salt, mantoquita, cobalt salt, molybdenum salt and zinc salt.
Also can there be stablizer, the medicament of for example cryostatic stabilization agent, sanitas, antioxidant, photostabilizer or other improvement chemistry and/or physical stability.
Normally, preparation of the present invention can contain above-mentioned active ingredient in the amount in 0.1 to 95 weight %, preferred 0.5 to the 90 weight % scope.
Active compound of the present invention can combine with other active compounds and exist, described other active compounds be for example can be commercial dosage form or by insecticide, poison bait agent, bactericide, miticide, nematocides, mycocide, growth regulator, the weedicide of the administration form of described formulation preparation.Aforementioned insecticide for example comprises, organophosphorus medicament, carbamate medicament, carboxylicesters medicament, chlorinated hydrocarbon type medicament, by the insect killing substance of microorganism preparation.
In addition, active compound of the present invention can be used as with the mix reagent of synergistic agent and exists, and this class preparation and administration form comprise can commercial preparation and administration form.Described synergistic agent itself need not to have activity, but but the effect of enhanced activity compound.
The content of the active compound of the present invention of administration form that can be commercial can change in wide scope.
The concentration of the active compound of using of the present invention can be in the scope of 0.0000001-100 weight %, preferably in the scope of 0.00001-1 weight %.
The usual manner that The compounds of this invention can be suitable for its administration form uses.It should be understood that The compounds of this invention also can be present in contains in other compositions, for example auxiliary agent or the composition of active components.The technician can select a kind of appropriate ingredients in composition described herein and known in the art, as to estimate to strengthen the performance that is considered to help predetermined application and uses.
All plants and plant parts all can be handled according to the present invention.The implication of plant is interpreted as all plants and plant population among the present invention, for example need and unwanted wild plant or crop plants (comprising naturally occurring crop plants).Crop plants can be can be by conventional plant breeding and optimum seeking method or the plant that obtains by biotechnology and genetic engineering method or the combination by preceding method, and described plant comprises transgenic plant and comprises the plant cultivars that is subjected to the plant breeder to weigh (plantbreeders ' rights) protection or is not subjected to its protection.The implication of plant parts be interpreted as plant all on the ground and underground position and plant organs, for example bud, leaf, Hua Hegen, the example that can mention have leaf, needle, stem, do, flower, sporophore, fruit, seed, root, stem tuber and rhizome.Plant parts also comprises harvested material, and asexual and sexual propagation thing, for example transplants, stem tuber, rhizome, branch and seed.
The processing of with active compound plant and plant parts being carried out according to the present invention, by conventional treatment method directly or compound effects is carried out in its environment, habitat or storage space, described conventional treatment method for example floods, sprays, evaporates, atomizes, broadcasts sowing, smears, injects, and, for the breeding thing, particularly, also can use one or more layers dressing for seed.
As mentioned above, can handle all plants and position thereof according to the present invention.In a kind of preferred embodiment, handled wild plant kind and plant cultivars, perhaps for example hybridize or protoplastis merges and the plant species and the plant cultivars that obtain by the biological breeding method of routine, and their position.In another kind of preferred embodiment, if handled by gene engineering method---suitable, combine with ordinary method---and transgenic plant and the plant cultivars (genetically modified organisms) and the position thereof of acquisition.Explain as above at term " position ", " position of plant " and " plant parts ".
Particularly preferably, the plant of handling according to the present invention is the commercially available plant cultivars that gets or using separately.The implication of plant cultivars is interpreted as the plant with new features (" feature ") that is obtained by conventional breeding, mutagenesis or recombinant DNA technology.They can be cultivar, biotype or genotype.
According to plant variety or plant cultivars, its plantation place and growth conditions (soil, weather, vegetative growth phase, nutrition (diet)), processing of the present invention also can produce super adding and (" working in coordination with ") effect.Can obtain the following effect that surpasses actual desired thus, for example reduce the rate of application of the material that can use according to the present invention and composition and/or widen its activity profile and/or improve its activity, improve plant-growth, improve high temperature or cold tolerance, raising to arid or to the tolerance of water or soil salt content, improve the quality of blooming, make simpler and easy, the accelerates maturing of gathering, raising gather productive rate, improve the quality of the product of gathering and/or improve its nutritive value, improve package stability and/or its processibility of the product of gathering.
Treat preferably that according to the present invention transgenic plant or the plant cultivars (obtaining by genetic engineering) handled comprise all plants of having accepted genetic material by genetic modification, described genetic material has been given described plant particularly advantageous, useful feature.The example of described feature have improve plant-growth, improve high temperature or cold tolerance, raising to arid or to the tolerance of water or soil salt content, improve the quality of blooming, make simpler and easy, the accelerates maturing of gathering, raising gather productive rate, improve the quality of the product of gathering and/or improve its nutritive value, improve package stability and/or its processing characteristics of the product of gathering.Further other examples of ben described feature have and improve the resistibility of plant to animal and microorganism nuisance, for example to the resistibility of insect, acarid, plant pathogenic fungi, bacterium and/or virus, and improve the tolerance of plant to some weeding active compound.The example of the transgenic plant that can mention is important crop plants, such as grain (wheat, rice), corn, soybean, potato, beet, tomato, pea and other vegetable varieties, cotton, tobacco, rape (oilseed rape) and fruit plant (fruit is apple, pears, citrus fruit and grape), ben is corn, soybean, potato, cotton, tobacco and rape.The ben toxin that is characterized as by in plant materials, forming, particularly the toxin that is formed in plant materials by the genetic material of Bacillus thuringiensis (Bacillus thurigiensis) (for example gene C ryIA (a), CryIA (b), CryIA (c), CryIIA, CryIIIA, CryIIIB2, Cry9c, Cry2Ab, Cry3Bb and CryIF and in conjunction with) improves the resistibility of plant (hereinafter referred to as " Bt plant ") to insect, arachnid, nematode and slug and snail.Also ben being characterized as by systemic acquired resistance (SAR), systemin, phytoalexin, releaser (elicitor) and resistant gene and corresponding marking protein and toxin improved the resistibility of plant to fungi, bacterium and virus.Ben in addition being characterized as improved the tolerance of plant to some weeding active compound, for example to the tolerance (for example " PAT " gene) of imidazolone type, sulfonylurea, glyphosate (glyphosate) or careless fourth phosphine (phosphinotricin).The gene of giving described required feature also can mutually combine in the transgenic plant body and exist.The example of " the Bt plant " that can mention has commercially available trade name to be
(for example corn, cotton, soybean),
(for example corn),
(for example corn),
(cotton),
(cotton) and
The corn variety of (potato), cotton variety, soybean varieties and potato kind.The example of the herbicide tolerant plant that can mention has commercially available trade name to be
(having glyphosate tolerant, for example corn, cotton, soybean),
(having careless fourth phosphine tolerance, for example rape),
(having imidazolinone-tolerant) and
Corn variety, cotton variety and the soybean varieties of (having the sulfonylurea tolerance, for example corn).The plant with Herbicid resistant that can mention (with the plant of the herbicide tolerant mode breeding of routine) comprises that name is called
The commercially available mutation of (for example corn).Certainly, more than narration also is applicable to the plant cultivars that has described gene expression characteristics or wait to develop gene expression characteristics, and described plant cultivars will be developed and/or goes on the market in future.
Listed plant can be handled according to the present invention in a kind of particularly advantageous mode with The compounds of this invention or composition.The preferable range of above-mentioned active compound or composition also is applicable to the processing of described plant.Lay special stress on is with compound of specifically mentioning in this specification sheets or compositions-treated plant.
Find that also The compounds of this invention also has strong insecticidal action to the insect that damages Industrial materials.
Can be used as example preferably but mention following insect without limitation:
Beetle, for example North America house longhorn beetle (Hylotrupes bajulus), Chlorophorus pilosis, furniture death watch beetle (Anobium punctatum), report dead death watch beetle (Xestobium rufovillosum), Ptilinus pectinicornis (Ptilinus pecticornis), Dendrobium pertinex, pine death watch beetle (Ernobius mollis), Priobium carpini, Lyctus brunneus Stephens (Lyctus brunneus), Africa powder moth (Lyctus africanus), south powder moth (Lyctus planicollis), quercitron moth (Lyctus linearis), pubescence powder moth (Lyctus pubescens), Trogoxylon aequale, minthea rugicollis (Minthes rugicollis), material bark beetle kind (Xyleborus spec.), Tryptodendron spec., coffee black long moth-eaten (Apate monachus), Mongolian oak long moth-eaten (Bostrychuscapucins), brown different wing long moth-eaten (Heterobostrychus brunneus), long moth-eaten plant (the Sinoxylon spec.) of sour jujube, dinoderus minutus (Dinoderus minutus);
Hymenopteran (Hymenopteron), for example big wood wasp (Sirexjuvencus), the big wood wasp of fir (Urocerus gigas), safe wood wasp (Urocerus gigas taignus), the Urocerusaugur of strengthening;
Termite, for example European kalotermitid (Kalotermes flavicollis), a fiber crops heap sand termite (Cryptotermes brevis), ash point different termite (Heterotermes indicola), American-European reticulitermes flavipe (Reticulitermes flavipes), Sang Te reticulitermes flavipe (Reticulitermessantonensis), southern Europe reticulate pattern termite (Reticulitermes lucifugus), Darwin Australia termite (Mastotermes darwiniensis), the ancient termite (Zootermopsisnevadensis) in Nevada, Coptotermes formosanus Shtrari (Coptotermes formosanus);
Moth (Bristletail), for example silverfish.
The implication of the Industrial materials among the present invention is interpreted as the non-living body material, for example, and preferred plastics, tackiness agent, sizing material, paper and cardboard, leather, timber, and timber products and coating composition through processing.
If suitable, describedly promptly also can contain other sterilants, and if suitablely also can contain one or more sterilant with composition.
About other additives of available, can be referring to above-mentioned sterilant and sterilant.
The compounds of this invention can be used for protecting the object that contacts with salt water or slightly salty, particularly hull, sieve, net, buildings, harbour and signalling system equally, in case dirt.
In addition, The compounds of this invention can be individually or is combined with other active compounds and as stain control agent.
In family expenses, health and storage product protection; described active compound also is suitable for preventing and treating the animal nuisance of finding in the enclosed space; particularly insect, arachnid and acarid, described enclosed space is residence, factory floor, office, compartment etc. for example.They can be individually or combine with other active compounds and auxiliary agent and be used for the described insect of family expenses desinsection product control.They have activity to sensitivity and resistance species and to whole etap.Described insect comprises:
Scorpionida (Scorpionidea), for example yellow scorpion (Buthus occitanus) in Mediterranean Sea.
Acarina, for example adobe tick (Argas persicus), argas reflexus (Argasreflexus), tongue mite subspecies (Bryobia ssp.), Dermanyssus gallinae, sweet mite (Glyciphagusdomesticus) is had a liking for by family, tampan tick (Ornithodorus moubat), brown dog tick (Rhipicephalus sanguineus), eutrombicula alfreddugesi (Trombicula alfreddugesi), Neutrombicula autumnalis, the spy has a liking for skin mite (Dermatophagoidespteronissimus), method is had a liking for skin mite (Dermatophagoides forinae).
Araneida (Araneae), for example catching bird spider (Aviculariidae), circle spider (Araneidae).
Opiliones (Opiliones), for example chelifer (Pseudoscorpiones chelifer), Pseudoscorpiones cheiridium, long abnormal blind spider (Opiliones phalangium).
Isopoda, for example comb beach louse, ball pillworm.
Doubly sufficient order, for example Blaniulus guttulatus, mountain cricket Eimeria (Polydesmus spp.).
Lip foot order, for example DIWUGONG belongs to.
Silverfish order (Zygentoma), for example the comb silverfish belongs to (Ctenolepisma spp.), silverfish, robber fireworm (Lepismodes inquilinus).
Blattodea, for example oriental cockroach, blatta germanica, Asia Lian (Blattella asahinai), leucophaea maderae, angle abdomen Lian belong to (Panchlora spp.), wooden Lian belongs to (Parcoblatta spp.), Australian cockroach (Periplaneta australasiae), periplaneta americana, big brown big Lian (Periplanetabrunnea), smoke Perilpaneta americana (Periplaneta fuliginosa), brown belt blattaria (Supellalongipalpa).
Jump order (Saltatoria), for example tame Xi.
Dermaptera, for example European earwig.
Isoptera, for example kalotermitid belongs to (Kalotermes spp.), Reticulitermes.
Corrodentia (Psocoptera), for example Lepinatus spp., powder corrodent belong to (Liposcelisspp.).
Coleoptera (Coleptera), for example Anthrenus, the moth-eaten genus of fur, khapra beetle genus, a long ostomatid (Latheticus oryzae), latent instep cuckoo Eimeria (Necrobia spp.), Ptinus, lesser grain borer, grain weevil (Sitophilus granarius), rice weevil (Sitophilus oryzae), sitophilus zea-mais (Sitophilus zeamais), Stegobium paniceum (Stegobium paniceum).
Diptera, for example Aedes aegypti (Aedes aegypti), Aedes albopictus (Aedesalbopictus), aedes taeniorhynchus (Aedes taeniorhynchus), Anopheles, calliphora erythrocephala, great number fiber crops horsefly (Chrysozona pluvialis), five band culex pipiens pollens (Culexquinquefasciatus), northern house (Culex pipiens), ring beak culex (Culextarsalis), Drosophila (Drosophila spp.), Fannia canicularis (Fannia canicularis), housefly, owl midge, flesh fly (Sarcophaga carnaria), Simulium, tatukira (Stomoxyscalcitrans), the Europe daddy-longlegs.
Lepidopteran, for example lesser wax-moth (Achroia grisella), greater wax moth, Indian meal moth (Plodiainterpunctella), stopper rain moth (Tinea cloacella), bag rain moth, curtain rain moth.
Siphonaptera, for example ctenocephalides canis, ctenocephalides felis, Pulex irritans (Pulex irritans), chigo (Tunga penetrans), Xanthopsyllacheopis.
Hymenoptera for example blazons hunchbacked ant (Camponotus herculeanus), black smelly ant (Lasius fuliginosus), black ant (Lasius niger), Lasius umbratus, MonomoriumMayr, Paravespula spp., Pavement Ant (Tetramorium caespitum).
Anoplura (Anoplura), for example head louse (Pediculus humanus capitis), body louse (Pediculus humanus corporis), Pemphigus spp., Phylloeravastatrix, crab louse (Phthirus pubis).
Heteroptera, for example cimex hemipterus (Cimex hemipterus), bed bug (Cimexlectularius), phodnius prolixus (Rhodinus prolixus), invasion triatomid (Triatomainfestans).
In the family expenses field of pesticides, can be used in combination with other suitable active compounds and especially preferred combination use, described suitable active compound is phosphoric acid ester, amino formate, pyrethroid, anabasine, growth regulator or other known insecticides class active compounds for example.
The compounds of this invention or composition---are preferably its suitable administration form---and can be used in the following product: aerosol, nothing are pressed spray product, for example pump spraying and atomizer spray, automatic atomization system, propellant, foaming agent, gelifying agent; Evaporation agent product with the evaporating plate of making by Mierocrystalline cellulose or polymkeric substance, liquid evaporation agent, gel and film evaporation agent, the evaporation agent of impeller driven, unpowered or passive vapo(u)rization system; Catch moth paper, catch the moth bag and catch moth glue, in the bait or Poison bait station (bait station) that is used for shedding as granule or powder agent.
Compound of the present invention or composition are particularly suitable for handling seed.The infringement that causes by insect to the major part of crop plants when seed is attacked during seed storage and planting seed just taken place during the plant germination and after just having germinateed after going in the soil.This stage is crucial especially, because the root of plant and bud are responsive especially in the growth, even minor harm also can cause whole strain plant death.Therefore by using suitable composition protection seed and germination plant to have special significant meaning.
To come pest control be long-term known and be the theme of updating by handling plant seed.But the processing of seed is with a series of problems that can not always solve with a kind of satisfactory way.Therefore, some are used for protecting the method for seed and germination plant like this to need exploitation, use crop protection agents in addition after this method need not after sowing or plant emerges.Wish to optimize the consumption of active compound in addition, so that provide the maximum protection of avoiding the insect invasion and attack to seed and germination plant, and used active compound can not damage plant itself.Particularly, methods for the treatment of seed also should be considered the intrinsic insecticidal properties of transgenic plant, reaches the best protection to seed and germination plant so that use the crop protection agents of minimum.
Therefore the present invention also is particularly related to a kind of the application of the invention compositions-treated seed and protects seed and germination plant to avoid the method for insect invasion and attack.The invention still further relates to the present composition and be used to handle seed avoids suffering the insect invasion and attack with the plant of protection seed and generation purposes.In addition, thus the invention still further relates to the present composition and handle the seed that obtains protection and avoided suffering the insect invasion and attack.
One of advantage of the present invention is that the peculiar internal absorption characteristic of the present composition means the invasion and attack that post avoids insect of planting of not only protecting seed itself but also protection to emerge and afterwards generate with these compositions-treated seeds.Use this method, can exempt at seeding time or thereafter soon to the processing immediately of crop.
In addition, must be considered to advantageously, The compounds of this invention or composition also can be used in particular for transgenic seed, can express the albumen of resisting insect by the plant that this seed generates.By handling this class seed with the present composition, some insect can be only expression by for example insecticidal proteins prevented and treated, the present composition also protects seed to avoid infringement in addition.
The seed of any plant variety of in agricultural, greenhouse, forest or gardening, using that The compounds of this invention or composition have been mentioned above being suitable for protecting.Especially, the form of described seed is: the seed of corn, peanut, Canadian rape, rape, opium poppy, soybean, cotton, beet (for example sugar beet and fodder beet), rice, jowar and grain, wheat, barley, oat, rye, Sunflower Receptacle, tobacco, potato or vegetables (for example tomato, Caulis et Folium Brassicae capitatae plant).The present composition is suitable for handling the seed of above mentioned fruit plant and vegetables equally.The present composition also is suitable for handling the seed of fruit plant referred to above and vegetables.The processing particularly important of corn, soybean, cotton, wheat and Canadian rape or brassica seed.
As mentioned above, handle also particularly important of transgenic seed with the present composition.The form of described seed is for containing the plant seed of at least a heterologous gene usually, and this heterologous gene domination particularly has the polypeptide expression of insecticidal properties.Herein, the heterologous gene of transgenic seed can come from microorganism for example genus bacillus (Bacillus), root nodule bacterium (Rhizobium), pseudomonas (Pseudomonas), Serratia (Serratia), wood mould (Trichoderma), Clavibacter, glomus (Glomus) or glutinous broom mould (Gliocladium).The present invention is particularly suitable for handling and contains at least a transgenic seed that bacillus and its gene product show opposing European corn borer (European corn borer) and/or the active heterologous gene of corn rootworm (corn rootworm) that comes from.Especially preferably come from the heterologous gene of Bacillus thuringiensis.
In the present invention, the present composition is applied to seed individually or with suitable formulations.Preferably, under a kind of steady state of the infringement during being enough to avoid handling, handle seed.Normally, seed can gather and sow between the random time point handle.Cob, shell, stem, epidermis, hair or pulp have been isolated and removed to normally used seed from plant.
Handle kind of a period of the day from 11 p.m. to 1 a.m, the amount that must be noted that the amount of the present composition that is applied to seed and/or other additives is usually selected in a kind of like this mode of plant that can influence the germination of seed or can not damage generation sharply.May have the situation of the active compound of phytotoxic effect especially under some rate of application, this point must keep in mind.
When being used to resist sanitary insect pest and grain storage pest, active compound of the present invention has good stability and also show good residual activity in timber and soil the alkali on the calcium carbonate material.
Normally, when being used to handle animal, active compound of the present invention can directly be used.The pharmaceutical composition that preferred their conducts can contain some pharmaceutically acceptable vehicle known in the art and/or auxiliary agent is used.
In veterinary applications and animal rearing, active compound is used (=administration) by following form of medication in a known way: carry out administration in the intestines with for example tablet, capsule, potus, drencs, granule, paste, pill, the form of feeding (feed-through) method, suppository; By for example injection (intramuscular, subcutaneous, intravenously, intraperitoneal etc.), implant and carry out administered parenterally; Pass through nasal administration; For example taking a shower (bathing) or the form of dipping, spraying, cast (pouring on) and drop, cleaning, dusting, and for example neck ring, ear tag, tail tag, limbs ligature (limb band), halter, concentrator marker etc. carry out percutaneous drug delivery by means of the moldings that contains active compound.Described active compound can be mixed with shampoo or the suitable preparation that can use in aerosol, non-pressurised sprays such as pump sprays and atomizer spray agent.
When being used for domestic animal, poultry, domestic animal etc., the preparation (for example pulvis, wettable powder [" WP "], emulsion, missible oil [" EC "] but flowing agent, homogeneous phase solution and suspension [" SC "]) that active compound of the present invention can be used as the active compound that contains 1-80 weight % amount directly uses or use dilution (for example diluting 000 times of 100-10) back, perhaps can be used as the chemical bath agent and uses.
When using in veterinary applications, active compound of the present invention can for example miticide, sterilant, wormer, protozoacide medicament combine and use with suitable synergistic agent or other active compounds.
To more specifically illustrate the present invention by embodiment.But the present invention should not only limit to these embodiment.
Synthetic embodiment 1
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } ethanamide (numbering 1-1)
Synthetic embodiment 1-1
Synthesizing of 4-tolyl aldehyde oxime
The solution of the second alcohol and water of 4-tolyl aldehyde (5g), hydroxy amine hydrochloric acid salt (4.34g) and sodium acetate (6.23g) was at room temperature stirred 1 hour.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain 4-tolyl aldehyde oxime (5g).
1H-NMR(CDCl3)δ：2.37(3H，s)，7.19(2H，d)，7.46(2H，d)，8.12(1H，s)
Synthetic embodiment 1-2
[5-(3, the 5-dichlorophenyl)-3-(4-aminomethyl phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole synthetic
Dimethyl formamide (20mL) solution of 4-tolyl aldehyde oxime (2g) and N-chlorosuccinimide (2.17g) was stirred 1 hour down at 55 ℃.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain N-hydroxy-4-methyl benzene carboxylic imino-chlorine (2g).With gained N-hydroxy-4-methyl benzene carboxylic imino-chlorine and 1,3-two chloro-5-[1-(trifluoromethyl) vinyl] toluene (50mL) vlil 8 hours of benzene (5.3g).Remove solvent under reduced pressure, residuum obtains [5-(3, the 5-dichlorophenyl) 3-(4-aminomethyl phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (5.0g) by the silica gel chromatography purifying.
1H-NMR(CDCl3)δ：2.37(3H，s)，3.87(2H，dd)，7.22-7.25(3H，m)，7.51-7.56(4H，m)。
Synthetic embodiment 1-3
3-[4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole synthetic
With 5-(3, the 5-dichlorophenyl)-3-(4-aminomethyl phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (5.3g), N-bromosuccinimide (3.7g) and 2, ethylene dichloride (40mL) vlil of 2 '-Diisopropyl azodicarboxylate (0.1g) 3 hours.After removing solvent under reduced pressure, residuum dilutes with t-butyl methyl ether, and with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 3-[4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (2.5g).
1H-NMR(CDCl3)δ：3.66-4.10(2H，m)，4.49(2H，s)，7.26-7.69(7H，m)。
Synthetic embodiment 1-4
2-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-1H-isoindole-1,3 (2H)-diketone synthetic
With 3-[4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4, the N of 5-dihydro-isoxazole (1-5g) and potassium phthalimide (0-61g), dinethylformamide (20mL) solution at room temperature stirred 8 hours.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.Use the anhydrous magnesium sulfate drying organic layer.Remove solvent under reduced pressure, by silica gel chromatography purifying residuum, obtain 3-[4-(brooethyl) phenyl then]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (0.8g).
1H-NMR(CDCl3)δ：3.85(2H，dd)，4.87(2H，s)，7.40-7.89(13H，m)。
Synthetic embodiment 1-5
1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } methylamine synthetic
With 2-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-methyl alcohol (5mL) solution of 1H-isoindole-1,3 (2H)-diketone (0.65g) and the hydrazine aqueous solution (0.07g) refluxed 1 hour.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } methylamine (0.2g).
1H-NMR(CDCl3)δ：3.89(2H，dd)，4.47(2H，s)，7.39-7.40(3H，m)，7.52-7.52(2H，m)，7.61-7.63(2H，m)。
Synthetic embodiment 1-6
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } ethanamide synthetic
To 1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } in tetrahydrofuran (THF) (5mL) solution of methylamine (0.2g) and triethylamine (0.08g), dropwise add Acetyl Chloride 98Min. (0.05g), and this mixture was at room temperature stirred 1 hour.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } ethanamide (0.05g).
1H-NMR(CDCl3)δ：2.04(3H，s)，3.88(2H，dd)，4.45(2H，d)，6.06(1H，s)，7.32(2H，d)，7.42-7.42(1H，m)，7.49-7.52(2H，m)，7.59-7.62(2H，m)。
Synthetic embodiment 2
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } ethanamide (numbering 1-1)
Synthetic embodiment 2-1
The N-{4-[(oxyimino) methyl] benzyl } ethanamide synthetic
N-(4-formyl radical benzyl) ethanamide (1.7g), hydroxy amine hydrochloric acid salt (1.0g) and the ethanol (10mL) of sodium acetate (1.0g) and the solution of water (6mL) were at room temperature stirred 1 hour.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain crude product N-{4-[(oxyimino) methyl]-benzyl } ethanamide (1.8g).
Synthetic embodiment 2-2
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } ethanamide synthetic
With the N-{4-[(oxyimino) methyl] benzyl } ethanamide (0.5g) is dissolved in N, and in the dinethylformamide (20mL), in this solution, add N-chlorosuccinimide (0.38g), and this mixture was at room temperature stirred 2 hours.In this reaction soln, add 1,3-two chloro-5-[1-(trifluoromethyl) vinyl] benzene (0.75g), and after this mixture is cooled to 0 ℃, the N that in this mixture, dropwise adds triethylamine (0.58g), dinethylformamide (2mL) solution at room temperature stirred this mixture 8 hours then.Add entry and, organic layer is washed and use anhydrous magnesium sulfate drying with saturated brine with behind the ethyl acetate extraction.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } ethanamide (0.3g).
1H-NMR(CDCl3)δ：2.04(3H，s)，3.88(2H，dd)，4.45(2H，d)，6.06(1H，s)，7.32(2H，d)，7.42-7.42(1H，m)，7.49-7.52(2H，m)，7.59-7.62(2H，m)。
Synthetic embodiment 3
N-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-N-(pyridine-2-ylmethyl) ethanamide (numbering 1-15)
Synthetic embodiment 3-1
3-[3-bromo-4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole synthetic
With 3-(3-bromo-4-aminomethyl phenyl)-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (1.2g), N-bromosuccinimide (0.54g) and 2, ethylene dichloride (20mL) vlil of 2 '-Diisopropyl azodicarboxylate (0.05g) 3 hours.Remove solvent under reduced pressure, residuum dilutes with t-butyl methyl ether, and with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, and residuum passed through the silica gel chromatography purifying, obtain 3-[3-bromo-4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (1.0g).
1H-NMR(CDCl3)δ：3.86(2H，dd)，4.59(2H，s)，7.46-7.6?1(5H，m)，7.85-7.86(1H，m)。
Synthetic embodiment 3-2
1-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl }-N-(pyridine-2-ylmethyl) methylamine synthetic
With 3-[3-bromo-4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4, acetonitrile (20mL) vlil of 5-dihydro-isoxazole (1.8g), 2-aminomethyl pyridine (0.38g) and salt of wormwood (0.97g) 3 hours.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, and residuum passed through the silica gel chromatography purifying, obtain 1-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl }-N-(pyridine-2-ylmethyl) methylamine (1.0g).
1H-NMR(CDCl3)δ：3.67(1H，d)，3.95-3.96(4H，m)，4.03-4.09(1H，m)，7.17-7.19(1H，m)，7.31-7.34(1H，m)，7.43-7.43(1H，m)，7.49-7.52(2H，m)，7.57-7.58(2H，m)，7.62-7.69(1H，m)，7.82-7.85(1H，m)，8.56-8.58(1H，m)。
Synthetic embodiment 3-3
N-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-N-(pyrodin-2-ylmethyl) ethanamide synthetic
To 1-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl-tetrahydrofuran (THF) (5mL) solution of N-(pyridine-2-ylmethyl) methylamine (0.22g) and triethylamine (0.06g) in, dropwise add Acetyl Chloride 98Min. (0.04g), and this mixture was at room temperature stirred 1 hour.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain N-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-N-(pyrodin-2-ylmethyl) ethanamide (0.15g).
1H-NMR(CDCl3)δ：2.10-2.22(3H，m)，3.63-4.13(2H，m)，4.63-4.74(4H，m)，7.14-7.90(9H，m)，8.51-8.59(1H，m)。
Synthetic embodiment 4
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-nitrobenzyl } ethanamide (1-60) synthetic
Synthetic embodiment 4-1
Synthesizing of 4-methyl-3-nitro phenyl aldehyde
Under refrigerative condition on the rocks, dioxane (30mL) solution of 4-methyl-3-nitro Benzoyl chloride (5.5g) is dropwise added in the solution of entry (30mL), dioxane (30mL) and sodium borohydride (2.5g).This reaction soln was refluxed 1 hour, and after the cooling, this solution is passed through diatomite filtration.In filtrate, add entry, mixture ethyl acetate extraction, and organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain the crude product (4g) of (4-methyl-3-nitro phenyl) methyl alcohol.
This crude product is dissolved in methylene dichloride (200mL), in this solution, adds Manganse Dioxide (20g), and this mixture was at room temperature stirred 10 hours.Behind this reaction mixture suction filtration, remove solvent under reduced pressure, then residuum is passed through the silica gel chromatography purifying, obtain 4-methyl-3-nitro phenyl aldehyde (3.5g).
1H-NMR(CDCl3)δ：2.70(3H，s)，7.55(1H，d)，8.03(1H，dd)，8.46(1H，d)，10.04(1H，s)。
Synthetic embodiment 4-2
5-(3, the 5-dichlorophenyl)-3-(4-methyl-3-nitro phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole synthetic
Under refrigerative condition on the rocks, tetrahydrofuran (THF) (50mL) solution of 4-methyl-3-nitro phenyl aldehyde (3.5g) is dropwise added in the solution of the tetrahydrofuran (THF) (50mL) of hydroxy amine hydrochloric acid salt (3.0g) and sodium acetate (4.0g) and water (50mL), and after dropwise adding is finished, this mixture was at room temperature stirred 1 hour.This reaction soln dilute with water is used ethyl acetate extraction then, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain the crude product (3.5g) of 4-methyl-3-nitro benzaldoxime.
This crude product is dissolved in N, in the dinethylformamide (30mL), and in this solution, adds N-chlorosuccinimide (1.4g), and this mixture was stirred 1 hour down at 55 ℃.After stirring is finished, under refrigerative condition on the rocks, in this mixture, add 1,3-two chloro-5-[1-(trifluoromethyl) vinyl] benzene (2.5g), triethylamine (1.2g), and this mixture at room temperature stirred 10 hours.The reaction soln dilute with water is used ethyl acetate extraction then, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum is passed through the silica gel chromatography purifying, obtain 5-(3, the 5-dichlorophenyl)-3-(4-methyl-3-nitro phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (2.1g).
1H-NMR(CDCl3)δ：2.63(3H，s)，3.72(1H，d)，4.10(1H，d)，7.43-7.51(4H，m)，7.88-7.91(1H，m)，8.15-8.16(1H，m)。
Synthetic embodiment 4-3
3-[4-(brooethyl)-3-nitrophenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole synthetic
With 5-(3, the 5-dichlorophenyl)-3-(4-methyl-3-nitro phenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (1.9g), N-bromosuccinimide (0.9g) and 2, the dichloroethane solution reflux of 2 '-Diisopropyl azodicarboxylate (0.1g) 3 hours.Reaction soln washes with water, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 3-[4-(brooethyl)-3-nitrophenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (1.2g).
1H-NMR(CDCl3)δ：3.73(1H，d)，4.11(1H，d)，4.84(2H，s)，7.44-7.68(4H，m)，7.97-8.00(1H，m)，8.24-8.24(1H，m)。
Synthetic embodiment 4-4
1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-nitrophenyl } methylamine synthetic
Under refrigerative condition on the rocks, with 3-[4-(brooethyl)-3-nitrophenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4, tetrahydrofuran (THF) (10mL) solution of 5-dihydro-isoxazole (1.0g) dropwise adds 28% the ammonia (aqueous solution, 5mL) and in the solution of the tetrahydrofuran (THF) (10mL) of tetrabutylammonium iodide (0.05g) and methyl alcohol (20mL), then this mixture was at room temperature stirred 10 hours.The reaction soln dilute with water is used ethyl acetate extraction then, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-nitrophenyl } methylamine (0.8g).
1H-NMR(CDCl3)δ：3.74(1H，d)，3.94-4.18(3H，m)，7.43-7.52(3H，m)，7.77-7.79(1H，m)，7.97-8.00(1H，m)，8.20-8.24(1H，m)。
Synthetic embodiment 4-5
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-nitrobenzyl } ethanamide (1-60) synthetic
Under refrigerative condition on the rocks, to 1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-nitrophenyl } in methylene dichloride (50mL) solution of methylamine (0.3g) and diacetyl oxide (0.1g), dropwise add methylene dichloride (5mL) solution of triethylamine (0.1g), then this mixture was at room temperature stirred 1 hour.This reaction soln dilute with water is then with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-nitrobenzyl } ethanamide (0.2g).
1H-NMR(CDCl3)δ：2.04(3H，s)，3.72(1H，d)，4.11(1H，d)，4.69(2H，d)，6.27-6.29(1H，m)，7.45-7.49(3H，m)，7.80-7.91(2H，m)，8.29(1H，d)
Synthetic embodiment 5
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-methyl-benzyl } ethanamide (numbering 1-63)
Synthetic embodiment 5-1
Synthesizing of 4-formyl radical-2-methyl-toluate
Under-70 ℃, in tetrahydrofuran (THF) (100mL) solution of 4-bromo-2-tolyl acid (10g), add hexane (60mL) solution of 1.6M n-Butyl Lithium.This reaction mixture after stirring 1 hour under-40 ℃, is being added N, tetrahydrofuran (THF) (10mL) solution of dinethylformamide (10mL) in this mixture under-70 ℃.After-70 ℃ stirring also was warmed to room temperature in 1 hour then down, pour in the ice this mixture and dilute with water this mixture.Water layer is with hexane wash and use the concentrated hydrochloric acid acidifying, and with the throw out ethyl acetate extraction.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain the crude product (5g) of 4-formyl radical-2-tolyl acid.
This crude product is dissolved in methylene dichloride (50mL) and the methyl alcohol (15.0g), and with 1-ethyl-3-(3-dimethylamino-propyl group) carbodiimide hydrochloride (12.0g), N, N-dimethyl aminopyridine (8.0g) adds in this solution, and this mixture was at room temperature stirred 10 hours.Reaction mixture 2N salt acid elution, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum is passed through the silica gel chromatography purifying, obtain 4-formyl radical-2-methyl-toluate (1.3g).
1H-NMR(CDCl3)δ：2.64(3H，s)，3.90(3H，s)，7.73-7.76(2H，m)，7.98-8.02(1H，m)，10.07(1H，s)。
Synthetic embodiment 5-2
4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-methyl-toluate synthetic
Under refrigerative condition on the rocks; tetrahydrofuran (THF) (50mL) solution of 4-formyl radical-2-methyl-toluate (1.3g) is dropwise added in the solution of hydroxy amine hydrochloric acid salt (1.0g) in tetrahydrofuran (THF) (50mL) and the water (50mL), sodium acetate (1.2g); and after dropwise adding is finished, this mixture was at room temperature stirred 1 hour.The reaction mixture dilute with water is used ethyl acetate extraction then, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain the 4-[(oxyimino) methyl]-crude product (1.3g) of 2-methyl-toluate.
This crude product is dissolved in N, and dinethylformamide (30mL) adds N-chlorosuccinimide (1.0g) then in this solution, and this mixture was stirred 1 hour down at 55 ℃.After stirring is finished, under refrigerative condition on the rocks, in this mixture, add 1,3-two chloro-5-[1-(trifluoromethyl) vinyl] benzene (1.7g) and triethylamine (0.8g), at room temperature stirred this mixture 10 hours then.The reaction mixture dilute with water is used ethyl acetate extraction then, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-methyl-toluate (1.9g).
1H-NMR(CDCl3)δ：2.63(3H，s)，3.68(1H，d)，3.91(3H，s)，4.11(2H，d)，7.42-7.54(5H，m)，7.95-7.96(1H，m)。
Synthetic embodiment 5-3
1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-aminomethyl phenyl } methylamine synthetic
Under refrigerative condition on the rocks, with 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-tetrahydrofuran (THF) (30mL) solution of 2-methyl-toluate (1.0g) dropwise adds in tetrahydrofuran (THF) (50mL) solution of lithium aluminum hydride (0.1g), and after adding is finished, this mixture was at room temperature stirred 1 hour.Reaction soln is fallen on ice, add 2N hydrochloric acid (30mL) then in batches.With this mixture ethyl acetate extraction, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain the crude product (0.9g) of { 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-2-aminomethyl phenyl } methyl alcohol.
This crude product is dissolved in methylene dichloride (50mL), and in this solution, adds triethylamine (0.3g).Under refrigerative condition on the rocks, dropwise add methylene dichloride (10mL) solution of methylsulfonyl chloride (0.3g) then, and this mixture was at room temperature stirred 1 hour.This reaction mixture is washed with water, and use the anhydrous magnesium sulfate drying organic layer.Remove solvent under reduced pressure,, obtain 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl then by silica gel chromatography purifying residuum]-crude product (1.0g) of 2-methyl-benzyl mesylate.
Under refrigerative condition on the rocks, tetrahydrofuran (THF) (10mL) solution of this crude product is dropwise added in the aqueous solution of the tetrahydrofuran (THF) (10mL) of 28% ammonia (5mL) and tetrabutylammonium iodide (0.05g) and methyl alcohol (20mL), and this mixture was at room temperature stirred 10 hours.The reaction mixture dilute with water is used ethyl acetate extraction then, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-aminomethyl phenyl } methylamine (0.4g).
1H-NMR(CDCl3)δ：2.39(3H，d)，3.69(1H，d)，3.89(2H，s)，4.11(1H，d)，7.42-7.49(6H，m)。
Synthetic embodiment 5-4
N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-methyl-benzyl } ethanamide synthetic
Under refrigerative condition on the rocks, to 1-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-aminomethyl phenyl } in methylene dichloride (50mL) solution of methylamine (0.2g) and diacetyl oxide (0.1g), dropwise add methylene dichloride (5mL) solution of triethylamine (0.1g), then this mixture was at room temperature stirred 1 hour.This reaction mixture is washed with water, and with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain N-{4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl]-the 2-methyl-benzyl } ethanamide (0.2g).
1H-NMR(CDCl3)δ：2.04(3H，s)，3.68(1H，d)，4.07(1H，d)，4.45(2H，d)，5.61-5.64(1H，m)，7.19-7.27(3H，m)，7.43-7.50(3H，m)
Synthetic embodiment 6
N-(cyano group 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] and phenyl } methyl)-N-(pyridine-2-ylmethyl)-ethanamide (numbering 1-11)
Synthetic embodiment 6-1
4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl aldehyde
In methylene dichloride (30mL) solution of { 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } methyl alcohol (1g), add activity oxidation manganese (1.8g), stirred 3 hours down with this mixture heating up and at 40 ℃ then.Reaction mixture is by behind the diatomite filtration, and concentrating under reduced pressure gained filtrate obtains 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl aldehyde (0.8g).
1H-NMR(CDCl3)δ：3.79-4.07(2H，m)，7.43-7.44(1H，m)，7.51-7.52(2H，m)，7.83-7.85(2H，m)，7.94-7.96(2H，m)，10.06(1H，s)
Synthetic embodiment 6-2
{ 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } [(pyridine-2-ylmethyl) amino] acetonitrile synthetic
To 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] in tetrahydrofuran (THF) (5mL) solution of phenyl aldehyde (0.30g), 2-aminomethyl pyridine (0.09g) and trimethylsilyl cyanide (0.08g), add lithium perchlorate (0.8g), then this mixture was at room temperature stirred 1 hour.With this reaction mixture with after the t-butyl methyl ether dilution, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum is passed through the silica gel chromatography purifying, obtain 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl [(pyridine-2-ylmethyl) amino] acetonitrile (0.15g).
1H-NMR(CDCl3)δ：3.65-3.83(5H，m)，7.05-7.57(11H，m)
Synthetic embodiment 6-3
N-(cyano group 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] and phenyl } methyl)-N-(pyridine-2-ylmethyl) ethanamide
To { 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } [(pyridine-2-yl) methyl] amino] in tetrahydrofuran (THF) (5mL) solution of acetonitrile (0.05g) and triethylamine (0.05g), dropwise add Acetyl Chloride 98Min. (0.03g), and this mixture was at room temperature stirred 1 hour.With this reaction mixture with after the t-butyl methyl ether dilution, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then by silica gel chromatography purifying residuum, obtain N-(cyano group { 4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] phenyl } methyl)-N-(pyridine-2-ylmethyl] ethanamide (0.10g).
1H-NMR(CDCl3)δ：2.28(3H，s)，3.86(2H，dd)，4.54-4.64(2H，m)，6.99-7.01(1H，m)，7.13-7.16(2H，m)，7.43-7.61(8H，m)，8.48-8.50(1H，m)
Synthetic embodiment 7
N-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl } second sulphamide (1-44) synthetic
With 3-[3-bromo-4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (0.3g) mixes with thioacetamide (0.04g), then this mixture is stirred 1 hour down at 80 ℃.Residuum obtains N-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl by the silica gel chromatography purifying] benzyl } second sulphamide (0.09g).
1H-NMR(CDCl3)δ：2.60(3H，s)，3.66-4.09(2H，m)，4.97(2H，d)，7.43-7.60(6H，m)，7.87(1H，d)
Synthetic embodiment 8
1-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-the 4-methyl isophthalic acid, 4-dihydro-5H-tetrazolium-5-ketone (numbering 1-55) synthesizes
With 3-[3-bromo-4-(brooethyl) phenyl]-5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole (0.3g), 1-methyl isophthalic acid, the N of 4-dihydro-5H-tetrazolium-5-ketone (0.06g) and salt of wormwood (0.16g), dinethylformamide (10mL) solution at room temperature stirred 3 hours.With this reaction mixture with after the t-butyl methyl ether dilution, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 1-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-the 4-methyl isophthalic acid, 4-dihydro-5H-tetrazolium-5-ketone (0.1g).
1H-NMR(CDCl3)δ：3.65-4.08(5H，m)，5.24(2H，s)，7.28-7.30(1H，m)，7.42-7.43(1H，m)，7.49-7.50(2H，m)，7.60-7.62(1H，m)，7.89-7.89(1H，m)。
Synthetic embodiment 9
N-{2-cyano group-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-N-(pyridine-2-ylmethyl) ethanamide (1-61) synthetic
Under argon gas atmosphere, to N-{2-bromo-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl-dimethyl formamide (20mL) solution of N-(pyrodin-2-ylmethyl) ethanamide (0.75g) in, add zinc cyanide (0.11g) and tetrakis triphenylphosphine palladium (0.29g), then this mixture was stirred 4 hours down at 80 ℃.With this reaction mixture with after the t-butyl methyl ether dilution, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain N-{2-cyano group-4-[5-(3, the 5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl] benzyl }-N-(pyridine-2-ylmethyl) ethanamide (0.6g).
1H-NMR(CDCl3)δ：2.27-2.31(3H，m)，3.75-4.06(2H，m)，4.68-4.87(4H，m)，7.17-7.96(9H，m)，8.49-8.57(1H，m)。
Synthetic embodiment 10
3-(4-aminomethyl phenyl)-5-(trifluoromethyl)-5-[3-(trifluoromethyl) phenyl]-4,5-dihydro-isoxazole synthetic
Synthetic embodiment 10-1
4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl)-3-[3-(trifluoromethyl) phenyl] fourth-1-ketone
With 2,2,2-three fluoro-1-[3-(trifluoromethyl) phenyl] tetrahydrofuran (THF) (30mL) solution of ethyl ketone (3.0g), 4-methyl acetophenone (1.1g) and lithium hydride (0.13g) stirred 3 hours down at 60 ℃.After this reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum passed through the silica gel chromatography purifying, obtain 4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl)-3-[3-(trifluoromethyl) phenyl] fourth-1-ketone (3.0g).
1H-NMR(CDCl3)δ：2.44(3H，s)，3.67-3.94(2H，m)，5.96(1H，s)，7.39-7.78(8H，m)。
Synthetic embodiment 10-2
4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl)-3-[3-(trifluoromethyl) phenyl] fourth-1-ketoxime
With 4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl)-3-[3-(trifluoromethyl) phenyl] ethanol (10mL) vlil 5 hours of fourth-1-ketone (1.0g), hydroxy amine hydrochloric acid salt (0.28g) and pyridine (0.42g).After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain 4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl)-3-[3-(trifluoromethyl) phenyl] fourth-1-ketoxime (1.0g).
1H-NMR(CDCl3)δ：2.30(3H，s)，3.39(1H，t，J＝6.8Hz)，4.02(1H，d，J＝13.6Hz)，5.25(1H，s)，6.94-7.69(8H，m)。
Synthetic embodiment 10-3
3-(4-aminomethyl phenyl)-5-(trifluoromethyl)-5-[3-(trifluoromethyl) phenyl]-4, the 5-dihydro-isoxazole
To 4,4,4-three fluoro-3-hydroxyl-1-(4-aminomethyl phenyl)-3-[3-(trifluoromethyl) phenyl] in tetrahydrofuran (THF) (10mL) solution of fourth-1-ketoxime (0.45g) and triphenyl phosphine (0.60g), add diethylazodicarboxylate (diethyl azodicarboxilate) (0.44g), and this mixture was at room temperature stirred 24 hours.After reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing, then with the organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, obtain 3-(4-aminomethyl phenyl)-5-(trifluoromethyl)-5-[3-(trifluoromethyl) phenyl]-4,5-dihydro-isoxazole (0.11g).
1H-NMR(CDCl3)δ：2.38(3H，s)，3.73(1H，d)，4.13(1H，d)，7.22-7.25(2H，m)，7.61-7.82(6H，m)
Synthetic embodiment 11
Synthesizing of 4-(4,4,4-three fluoro-3-hydroxyls-3-phenyl butyryl radicals) methyl benzoate
With 2,2, hexane (30mL) solution of 2-three fluoro-1-phenyl ethyl ketones (2.0g), 4-acetylbenzoic acid methyl esters (1.02g) and lithium hydride (0.13g) stirred 3 hours down at 40 ℃.After this reaction soln dilutes with t-butyl methyl ether, with this solution with water and saturated brine washing.The organic layer anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, then residuum is passed through the silica gel chromatography purifying, obtain 4-(4,4,4-three fluoro-3-hydroxyls-3-phenyl butyryl radicals) methyl benzoate (1.2g).
1H-NMR(CDCl3)δ：3.68(1H，d)，3.96(3H，s)，4.06(1H，d)，5.43(1H，s)，7.34-7.37(4H，m)，7.58-7.61(3H，m)，7.96-8.16(2H，m)
Synthetic embodiment 12
N-[(4-{5-[3,4-two chloro-5-(trifluoromethyl) phenyl]-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl } naphthalene-1-yl) methyl] ethanamide (7-128) synthetic
N-chlorosuccinimide (0.06g) is added N-({ 4-[(oxyimino) methyl] naphthalene-1-yl } methyl) N of ethanamide (0.1g), in dinethylformamide (10ml) solution, and at room temperature stirred this reaction mixture 2 hours.In this reaction mixture, add 1,2-two chloro-3-(trifluoromethyl)-5-[1-(trifluoromethyl) vinyl] benzene (0.75g) and saleratus (0.13g), and this mixture at room temperature stirred 8 hours.Water is poured in this reaction mixture, and it is used ethyl acetate extraction.Organic layer salt water washing, and use anhydrous magnesium sulfate drying.Remove solvent under reduced pressure, and, obtain N-[(4-{5-[3,4-two chloro-5-(trifluoromethyl) phenyl residuum silica gel column chromatography purifying]-5-(trifluoromethyl)-4,5-dihydro-isoxazole-3-yl } naphthalene-1-yl) methyl] ethanamide (0.1g).
1H-NMR(CDCl3)δ：2.15(3H，s)，3.89(1H，d)，4.30(1H，d)，4.88(2H，d)，5.97-6.00(1H，m)，7.42-7.44(2H，m)，7.61-7.66(2H，m)，7.87-7.91(1H，m)，8.01-8.05(2H，m)，8.84-8.88(1H，m)
Method by being similar to above-mentioned synthetic embodiment and be shown among the table 1-9 with its physical values according to formula of the present invention (I) compound and intermediate thereof that detailed described method above obtains.The compound that obtains among the synthetic embodiment mentioned above also is shown in the following table.
Table 1
| Numbering | ??(X)l | ??R | ??Y | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??1-1 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-2 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??MeCO | ??MeCO | ??CH | ??1 |
| ??1-3 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??MeCO | 2-pyridyl-CO | ??CH | ??1 |
| ??1-4 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??HCO | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-5 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??MeCO | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-6 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??EtCO | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-7 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??Me2NCO | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-8 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??MeSO2 | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-9 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | 2-pyridyl-CO | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-10 | 3,5-two Cl | ??CF3 | ??H | ??CN | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-11 | 3,5-two Cl | ??CF3 | ??H | ??CN | ??H | ??MeCO | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-12 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??HCO | ??H | ??CH | ??1 |
| ??1-13 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-14 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??MeCO | ??CH | ??1 |
| ??1-15 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | 2-pyridyl-CH2 | ??CH | ??1 |
| ??1-16 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | 3-pyridyl CH2 | ??CH | ??1 |
| ??1-17 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | 4-pyridyl-CH2 | ??CH | ??1 |
| ??1-18 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | Benzyl | ??CH | ??1 |
| ??1-19 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??1-20 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | Just-PrCO | ??H | ??CH | ??1 |
| ??1-21 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | Different-PrCO | ??H | ??CH | ??1 |
| ??1-22 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | Uncle-BuCO | ??H | ??CH | ??1 |
| ??1-23 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??CF3CO | ??H | ??CH | ??1 |
| ??1-24 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??PhCO | ??H | ??CH | ??1 |
| ??1-25 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | 2-pyridyl-CO | ??H | ??CH | ??1 |
| Numbering | ??(X)l | ??R | ??Y | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??1-109 | ??3-CH3-S??(O) | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-110 | ??3-CH3-S??(O)2 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-111 | ??3-CF3S | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-112 | ??3-CF3-S(??O) | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-113 | ??3-CF3-S(??O)2 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-114 | ??3-OH | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-115 | ??3-SH | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-116 | ??3-NH2 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-117 | ??3-NH-C??O-CH3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-118 | ??3-NH-C??O-CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-119 | ??3-NH-C??O2CH3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-120 | ??3-NH-C??O2-CH2-??CCl3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-121 | ??3-NH-S??O2CH3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-122 | ??3-NH-S??O2CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-123 | 3,5-two Cl | ??CF3 | ??NHCOC??F3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-124 | 3,5-two Cl | ??CF3 | ??NH-SO2??CH3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-125 | 3,5-two Cl | ??CF3 | ??NH-SO2??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-126 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??MeCO | ??H | ??CH | ??2 |
| ??1-127 | 3,5-two Br | ??CF3 | ??H | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-128 | ??3-F | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-129 | 3,4,5-three Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-130 | 3,5-two Cl-4-Me | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-131 | 3,4,5-three F | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-132 | 3,4,5-three Br | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-133 | 3,5-two Cl, 4-Br | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-134 | 3,5-two Cl, 4-Br | ??CE3 | ??Br | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??1-135 | 3,5-two Br, 4-Cl | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-136 | 3,5-two Br, 4-Cl | ??CF3 | ??Br | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??1-137 | 3,5-two Cl, 4-NH2 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| Numbering | ??(X)l | ??R | ??Y | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??1-138 | 3,5-two Br, 4-NH2 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-139 | 3,5-two Br, 4-NH2 | ??CF3 | ??Br | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??1-140 | 3,4-two Cl, 5-CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-141 | 3,5-two Cl, 4-CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-142 | 3,5-two Cl, 4-CF3 | ??CF3 | ??Br | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??1-143 | ??3-Cl，??5-CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-144 | ??3-Cl，??4-CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-145 | ??3-Br，??5-CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-146 | ??3-Br，??4-CF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-147 | ??3-CF3，??4-F | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??1-148 | ??3-Cl，??5-SCF3 | ??CF3 | ??Br | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
Table 2
| Numbering | ??(X)l | ??R | ??Y | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??2-1 | 3,5-two Cl | ??CF3 | ??H | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-2 | 3,5-two Cl | ??CF3 | ??CH3 | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-3 | 3,5-two Cl | ??CF3 | ??F | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-4 | 3,5-two Cl | ??CF3 | ??Cl | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-5 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-6 | 3,5-two Cl | ??CF3 | ??I | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-7 | 3,5-two Cl | ??CF3 | ??NO2 | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-8 | 3,5-two Cl | ??CF3 | ??CN | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-9 | 3,5-two Cl | ??CF3 | ??MeS | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-10 | 3,5-two Cl | ??CF3 | ??MeSO | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-11 | 3,5-two Cl | ??CF3 | ??MeSO2 | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-12 | 3,5-two Cl | ??CF3 | ??CF3S | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-13 | 3,5-two Cl | ??CF3 | ??CF3-S(O) | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-14 | 3,5-two Cl | ??CF3 | ??CF3-S(O)2 | ??H | ??H | ??H | ??H | ??CH | ??1 |
| Numbering | ??(X)l | ??R | ??Y | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??2-72 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??2 |
| ??2-73 | ??3-NH2 | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-74 | ??3-NHCOCH3 | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-75 | ??3-NHCOCF3 | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-76 | ??3-NHCO2CH3 | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-77 | ??3-NHCO2CH2CCl3 | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-78 | ??3-NHSO2CH3 | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-79 | ??3-NHSO2CF3 | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-80 | 3,5-two Cl | ??CF3 | ??NHCOCF3 | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-81 | 3,5-two Cl | ??CF3 | ??NHSO2CH3 | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-82 | 3,5-two Cl | ??CF3 | ??NHSO2CF3 | ??H | ??H | ??H | ??H | ??CH | ??1 |
| ??2-83 | 3,5-two Br | ??CF3 | ??Br | ??H | ??H | ??H | ??H | ??CH | ??1 |
Table 4
Table 5
| Numbering | ??(X)l | ??R | ??Y | ??R 1 | ??R 2 | ??A | ??n |
| ??4-1 | 35-two Cl | ??CF3 | ??H | ??H | ??H | ??CH | ??1 |
| ??4-2 | 3,5-two Cl | ??CF3 | ??Me | ??H | ??H | ??CH | ??1 |
| ??4-3 | 35-two Cl | ??CF3 | ??F | ??H | ??H | ??CH | ??1 |
| ??4-4 | 3,5-two Cl | ??CF3 | ??Cl | ??H | ??H | ??CH | ??1 |
| ??4-5 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-6 | 3,5-two Cl | ??CF3 | ??I | ??H | ??H | ??CH | ??1 |
| ??4-7 | 3,5-two Cl | ??CF3 | ??NO2 | ??H | ??H | ??CH | ??1 |
| ??4-8 | 3,5-two Cl | ??CF3 | ??CN | ??H | ??H | ??CH | ??1 |
| ??4-9 | 3,5-two Cl | ??CF3 | ??MeS | ??H | ??H | ??CH | ??1 |
| ??4-10 | 3,5-two Cl | ??CF3 | ??MeSO | ??H | ??H | ??CH | ??1 |
| ??4-11 | 3,5-two Cl | ??CF3 | ??MeSO2 | ??H | ??H | ??CH | ??1 |
| ??4-12 | 3,5-two Cl | ??CF3 | ??CF3S | ??H | ??H | ??CH | ??1 |
| ??4-13 | 3,5-two Cl | ??CF3 | ??CF3S(O) | ??H | ??H | ??CH | ??1 |
| ??4-14 | 3,5-two Cl | ??CF3 | ??CF3S(O)2 | ??H | ??H | ??CH | ??1 |
| ??4-15 | 3,5-two Cl | ??CF3 | ??OMe | ??H | ??H | ??CH | ??1 |
| ??4-16 | 3,5-two Cl | ??CF3 | ??OCF3 | ??H | ??H | ??CH | ??1 |
| ??4-17 | 3,5-two Cl | ??CF3 | ??OH | ??H | ??H | ??CH | ??1 |
| ??4-18 | 3,5-two Cl | ??CF3 | ??SH | ??H | ??H | ??CH | ??1 |
| ??4-19 | 3,5-two Cl | ??CF3 | ??NH2 | ??H | ??H | ??CH | ??1 |
| ??4-20 | 3,5-two Cl | ??CF3 | ??NHCOMe | ??H | ??H | ??CH | ??1 |
| ??4-21 | 3,5-two Cl | ??CF3 | ??NHCO2Me | ??H | ??H | ??CH | ??1 |
| ??4-22 | 3,5-two Cl | ??CF3 | ??NHCO2CH2CCl3 | ??H | ??H | ??CH | ??1 |
| ??4-23 | 3,5-two Br | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-24 | 3,4-two Cl | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-25 | 3,4,5-three Cl | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-26 | 3,5-two Cl-4-Me | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-27 | ??3-F | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-28 | ??3-Cl | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-29 | ??3-CF3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-55 | ??3-CF3 | ??CF3 | ??H | ??H | ??H | ??CH | ??1 |
| ??4-30 | ??4-CF3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-31 | 3,5-two CF3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-32 | ??3-NO2 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-33 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-34 | ??3-CH3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-35 | ??3-CH3O | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-36 | ??3-CN | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-37 | ??3-CF3O | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-38 | ??3-CH3S | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-39 | ??3-CH3S(O) | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-40 | ??3-CH3S(O)2 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-41 | ??3-CF3S | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-42 | ??3-CF3S(O) | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-43 | ??3-CF3S(O)2 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-44 | ??3-OH | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-45 | ??3-SH | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-46 | ??3-NH2 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-47 | ??3-NHCOCH3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-48 | ??3-NHCOCF3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-49 | ??3-NHCO2CH3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-50 | ??3-NHCO2CH2CCl3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-51 | ??3-NHSO2CH3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-52 | ??3-NHSO2CF3 | ??CF3 | ??Br | ??H | ??H | ??CH | ??1 |
| ??4-53 | 3,5-two Cl | ??CF3 | ??Br | ??Me | ??H | ??CH | ??1 |
| ??4-54 | 3,5-two Cl | ??CF3 | ??Br | ??H | ??H | ??N | ??1 |
Table 6
| Numbering | ??(X)l | ??R | ??Y | ??R 5 | ??A |
| ??5-1 | ??H | ??CF3 | ??H | ??Me | ??CH |
| ??5-2 | 3,5-two Cl | ??CF3 | ??H | ??Me | ??CH |
| ??5-3 | 3,5-two Cl | ??CF3 | ??Me | ??Me | ??CH |
| ??5-4 | 3,5-two Cl | ??CF3 | ??F | ??Me | ??CH |
| ??5-5 | 3,5-two Cl | ??CF3 | ??Cl | ??Me | ??CH |
| ??5-6 | 3,5-two Cl | ??CF3 | ??Br | ??Me | ??CH |
| ??5-7 | 3,5-two Cl | ??CF3 | ??I | ??Me | ??CH |
| ??5-8 | 3,5-two Cl | ??CF3 | ??NO2 | ??Me | ??CH |
| ??5-9 | 3,5-two Cl | ??CF3 | ??CN | ??Me | ??CH |
| ??5-10 | 3,5-two Cl | ??CF3 | ??MeS | ??Me | ??CH |
| ??5-11 | 3,5-two Cl | ??CF3 | ??MeSO | ??Me | ??CH |
| ??5-12 | 3,5-two Cl | ??CF3 | ??MeSO2 | ??Me | ??CH |
| ??5-13 | 3,5-two Cl | ??CF3 | ??CF3S | ??Me | ??CH |
| ??5-14 | 3,5-two Cl | ??CF3 | ??CF3S(O) | ??Me | ??CH |
| ??5-15 | 3,5-two Cl | ??CF3 | ??CF3S(O)2 | ??Me | ??CH |
| ??5-16 | 3,5-two Cl | ??CF3 | ??OMe | ??Me | ??CH |
| ??5-17 | 3,5-two Cl | ??CF3 | ??OCF3 | ??Me | ??CH |
| ??5-18 | 3,5-two Cl | ??CF3 | ??OH | ??Me | ??CH |
| ??5-19 | 3,5-two Cl | ??CF3 | ??SH | ??Me | ??CH |
| ??5-20 | 3,5-two Cl | ??CF3 | ??NH2 | ??Me | ??CH |
| ??5-21 | 3,5-two Cl | ??CF3 | ??NHCOMe | ??Me | ??CH |
| ??5-22 | 3,5-two Cl | ??CF3 | ??NHCO2Me | ??Me | ??CH |
| ??5-23 | 3,5-two Cl | ??CF3 | ??NHCO2CH2CCl3 | ??Me | ??CH |
| ??5-24 | 3,5-two Br | ??CF3 | ??Br | ??Me | ??CH |
| ??5-25 | 3,4-two Cl | ??CF3 | ??Br | ??Me | ??CH |
| ??5-26 | 3,4,5-three Cl | ??CF3 | ??Br | ??Me | ??CH |
| ??5-27 | 3,5-two Cl-4-Me | ??CF3 | ??Br | ??Me | ??CH |
| ??5-28 | ??3-F | ??CF3 | ??Br | ??Me | ??CH |
| ??5-29 | ??3-Cl | ??CF3 | ??Br | ??Me | ??CH |
| ??5-30 | ??3-CF3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-31 | ??4-CF3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-32 | 3,5-two CF3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-33 | ??3-NO2 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-34 | 3,5-two Cl | ??CF3 | ??Br | ??Me | ??CH |
| ??5-35 | ??3-CH3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-36 | ??3-CH3O | ??CF3 | ??Br | ??Me | ??CH |
| ??5-37 | ??3-CN | ??CF3 | ??Br | ??Me | ??CH |
| ??5-38 | ??3-CF3O | ??CF3 | ??Br | ??Me | ??CH |
| ??5-39 | ??3-CH3S | ??CF3 | ??Br | ??Me | ??CH |
| ??5-40 | ??3-CH3S(O) | ??CF3 | ??Br | ??Me | ??CH |
| ??5-41 | ??3-CH3S(O)2 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-42 | ??3-CF3S | ??CF3 | ??Br | ??Me | ??CH |
| ??5-43 | ??3-CF3S(O) | ??CF3 | ??Br | ??Me | ??CH |
| ??5-44 | ??3-CF3S(O)2 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-45 | ??3-OH | ??CF3 | ??Br | ??Me | ??CH |
| ??5-46 | ??3-SH | ??CF3 | ??Br | ??Me | ??CH |
| ??5-47 | ??3-NH2 | ??CF3 | ??Br | ??Me | ??CH |
| Numbering | ??(X)l | ??R | ??Y | ??R 5 | ??A |
| ??5-48 | ??3-NHCOCH3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-49 | ??3-NHCOCF3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-50 | ??3-NHCO2CH3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-51 | ??3-NHCO2CH2CCl3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-52 | ??3-NHSO2CH3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-53 | ??3-NHSO2CF3 | ??CF3 | ??Br | ??Me | ??CH |
| ??5-54 | 3,5-two Cl | ??CF3 | ??Br | ??Me | ??N |
| ??5-55 | 3,5-two Cl | ??CF3 | ??Br | ??Et | ??CH |
| ??5-56 | 3,5-two Cl | ??CF3 | ??Br | Uncle-Bu | ??CH |
Table 7
| Numbering | ??Y | ??R 1 | ??R 2 | ??R 4 | ??A | ??n |
| ??6-1 | ??H | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-2 | ??Me | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-3 | ??F | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-4 | ??Cl | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-5 | ??Br | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-6 | ??I | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-7 | ??NO2 | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-8 | ??CN | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-9 | ??MeS | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-10 | ??MeSO | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-11 | ??MeSO2 | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-12 | ??CF3S | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-13 | ??CF3S(O) | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-14 | ??CF3S(O)2 | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-15 | ??OCH3 | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-16 | ??OCF3 | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-17 | ??OH | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-18 | ??SH | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-19 | ??NH2 | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-20 | ??NHCOMe | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-21 | ??NHCO2Me | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-22 | ??NHCO2CH2CCl3 | ??H | ??H | ??MeCO | ??CH | ??1 |
| ??6-23 | ??Br | ??H | ??H | ??MeCO | ??CH | ??2 |
| ??6-24 | ??Br | ??H | ??H | ??EtCO | ??CH | ??1 |
| ??6-25 | ??Br | ??H | ??H | Just-PrCO | ??CH | ??1 |
| ??6-26 | ??Br | ??H | ??H | Different-PrCO | ??CH | ??1 |
| ??6-27 | ??Br | ??H | ??H | Uncle-BuCO | ??CH | ??1 |
| ??6-28 | ??Br | ??H | ??H | ??CF3CO | ??CH | ??1 |
| ??6-29 | ??Br | ??H | ??H | ??PhCO | ??CH | ??1 |
| ??6-30 | ??Br | ??H | ??H | 2-pyridyl CO | ??CH | ??1 |
| ??6-31 | ??Br | ??H | ??H | 3-pyridyl CO | ??CH | ??1 |
| ??6-32 | ??Br | ??H | ??H | 4-pyridyl CO | ??CH | ??1 |
| ??6-33 | ??Br | ??H | ??H | ??2-F-PhCO | ??CH | ??1 |
| ??6-34 | ??Br | ??H | ??H | ??3-F-PhCO | ??CH | ??1 |
| Numbering | ??Y | ??R 1 | ??R 2 | ??R 4 | ??A | ??n |
| ??6-35 | ??Br | ??H | ??H | ??4-F-PhCO | ??CH | ??1 |
| ??6-36 | ??Br | ??H | ??H | ??2-Cl-PhCO | ??CH | ??1 |
| ??6-37 | ??Br | ??H | ??H | ??3-Cl-PhCO | ??CH | ??1 |
| ??6-38 | ??Br | ??H | ??H | ??4-Cl-PhCO | ??CH | ??1 |
| ??6-39 | ??Br | ??H | ??H | ??2-Br-PhCO | ??CH | ??1 |
| ??6-40 | ??Br | ??H | ??H | ??2-Me-PhCO | ??CH | ??1 |
| ??6-41 | ??Br | ??H | ??H | Vinyl CO | ??CH | ??1 |
| ??6-42 | ??Br | ??H | ??H | ??HCCCO | ??CH | ??1 |
| ??6-43 | ??Br | ??H | ??H | ??MeSO2 | ??CH | ??1 |
| ??6-44 | ??Br | ??H | ??H | ??CF3SO2 | ??CH | ??1 |
| ??6-45 | ??Br | ??H | ??H | ??MeHNCO | ??CH | ??1 |
| ??6-46 | ??Br | ??H | ??H | ??Me2NCO | ??CH | ??1 |
| ??6-47 | ??Br | ??H | ??H | ??MeOC(＝O) | ??CH | ??1 |
| ??6-48 | ??Br | ??H | ??H | ??MeSC(＝O) | ??CH | ??1 |
| ??6-49 | ??Br | ??H | ??H | ??MeCS | ??CH | ??1 |
| ??6-50 | ??Br | ??H | ??H | ??MeON(Me)CO | ??CH | ??1 |
| ??6-51 | ??Br | ??Me | ??H | ??MeCO | ??CH | ??1 |
| ??6-52 | ??Br | ??Me | ??H | ??MeCO | ??N | ??1 |
Table 8
| Numbering | ??(X)l | ??R | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??7-1 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-2 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??MeCO | ??CH | ??1 |
| ??7-3 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | 2-pyridyl CO | ??CH | ??1 |
| ??7-4 | 3,5-two Cl | ??CF3 | ??H | ??H | ??HCO | 2-pyridyl CH2 | ??CH | ??1 |
| ??7-5 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | 2-pyridyl CH2 | ??CH | ??1 |
| ??7-6 | 3,5-two Cl | ??CF3 | ??H | ??H | ??EtCO | 2-pyridyl CH2 | ??CH | ??1 |
| ??7-7 | 3,5-two Cl | ??CF3 | ??H | ??H | ??Me2NCO | 2-pyridyl CH2 | ??CH | ??1 |
| ??7-8 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeSO2 | 2-pyridyl CH2 | ??CH | ??1 |
| ??7-9 | 3,5-two Cl | ??CF3 | ??H | ??H | 2-pyridyl CO | 2-pyridyl CH2 | ??CH | ??1 |
| ??7-10 | 3,5-two Cl | ??CF3 | ??CN | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-11 | 3,5-two Cl | ??CF3 | ??CN | ??H | ??MeCO | 2-pyridyl CH2 | ??CH | ??1 |
| ??7-12 | 3,5-two Cl | ??CF3 | ??H | ??H | ??HCO | ??H | ??CH | ??1 |
| ??7-13 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | 3-pyridyl CH2 | ??CH | ??1 |
| ??7-14 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | 4-pyridyl CH2 | ??CH | ??1 |
| ??7-15 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | Benzyl | ??CH | ??1 |
| ??7-16 | 3,5-two Cl | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-17 | 3,5-two Cl | ??CF3 | ??H | ??H | Just-PrCO | ??H | ??CH | ??1 |
| ??7-18 | 3,5-two Cl | ??CF3 | ??H | ??H | Different-PrCO | ??H | ??CH | ??1 |
| ??7-19 | 3,5-two Cl | ??CF3 | ??H | ??H | Ring-type-PrCO | ??H | ??CH | ??1 |
| ??7-20 | 3,5-two Cl | ??CF3 | ??H | ??H | Uncle-BuCO | ??H | ??CH | ??1 |
| ??7-21 | 3,5-two Cl | ??CF3 | ??H | ??H | ??CF3CO | ??H | ??CH | ??1 |
| Numbering | ??(X)l | ??R | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??7-66 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??N＝CMe2 | ??CH | ??1 |
| ??7-67 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??OH | ??CH | ??1 |
| ??7-68 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??MeO | ??CH | ??1 |
| ??7-69 | 3,4-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-70 | 3,4,5-three Cl | ??CH3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-71 | 3,4,5-three Cl | ??CH3 | ??H | ??H | Ring-type-PrCO | ??H | ??CH | ??1 |
| ??7-72 | 3,4,5-three Cl | ??CH3 | ??H | ??H | ??CF3CH2CO | ??H | ??CH | ??1 |
| ??7-73 | 3,5-two Cl-4-Me | ??CH3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-74 | ??3-F | ??CH3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-75 | ??3-Cl | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-76 | ??3-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-77 | ??4-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-78 | 3,5-two CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-79 | ??3-NO2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-80 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??H | ??N | ??1 |
| ??7-81 | ??3-CH3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-82 | ??3-CH3O | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-83 | ??3-CN | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-84 | ??3-CF3O | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-85 | ??3-CH3S | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-86 | ??3-CH3S(O) | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-87 | ??3-CH3S(O)2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-88 | ??3-CF3S | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-89 | ??3-CF3S(O) | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-90 | ??3-CF3S(O)2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-91 | ??3-OH | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-92 | ??3-SH | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-93 | ??3-NH2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-94 | ??3-NHCOCH3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-95 | ??3-NHCOCF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-96 | ??3-NHCO2CH3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-97 | ??3-NHCO2CH2CCl3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-98 | ??3-NHSO2CH3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-99 | ??3-NHSO2CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-100 | 3,5-two Cl | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??2 |
| ??7-101 | 3,5-two Br | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-102 | 3,5-two Br | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-103 | 3,4,5-three Cl | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-104 | 3,4,5-three Cl | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-105 | 3,4,5-three Cl | ??CF3 | ??H | ??H | ??CF3CH2CO | ??H | ??CH | ??1 |
| ??7-106 | 3,4,5-three F | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-107 | 3,4,5-three F | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-108 | 3,4,5-three Br | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-109 | 3,4,5-three Br | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| Numbering | ??(X)l | ??R | ??R 1 | ??R 2 | ??R 4 | ??R 3 | ??A | ??n |
| ??7-110 | 3,5-two Cl, 4-Br | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-111 | 3,5-two Cl, 4-Br | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-112 | 3,5-two Br, 4-Cl | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-113 | 3,5-two Br, 4-Cl | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-114 | 3,5-two Cl, 4-I | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-115 | 3,5-two Cl, 4-I | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-116 | 3,5-two I | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-117 | 3,5-two I | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-118 | 3,5-two Cl, 4-NH2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-119 | 3,5-two Cl, 4-NH2 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-120 | 3,5-two Br, 4-NH2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-121 | 3,5-two B r, 4-NH2 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-122 | 3,5-two I, 4-NH2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-123 | 3,5-two I, 4-NH2 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-124 | 3,5-two Cl, 4-NHAc | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-125 | 3,5-two Cl, 4-NHAc | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-126 | 3,5-two Cl, 4-NHCOCF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-127 | 3,5-two Cl, 4-NHCOCF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-128 | 3,4-two Cl, 5-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-129 | 3,4-two Cl, 5-CF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-130 | 3,5-two Cl, 4-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-131 | 3,5-two Cl, 4-CF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-132 | ??3-Cl，5-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-133 | ??3-Cl，5-CF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-134 | ??3-Cl，4-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-135 | ??3-Cl，4-CF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-136 | ??3-Br，5-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-137 | ??3-Br，5-CF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-138 | ??3-Br，4-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-139 | ??3-Br，4-CF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-140 | ??3-I，5-CF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-141 | ??3-I，5-CF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-142 | ??3-CF3，4-F | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-143 | ??3-CF3，4-F | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-144 | ??3-Cl，5-SCF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-145 | ??3-Cl，5-SCF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-146 | ??4-NH2 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-147 | ??4-NH2 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
| ??7-148 | ??4-NH2 | ??CF3 | ??H | ??H | ??CF3CH2CO | ??H | ??CH | ??1 |
| ??7-149 | ??3-Cl，4-SCF3 | ??CF3 | ??H | ??H | ??MeCO | ??H | ??CH | ??1 |
| ??7-150 | ??3-Cl，4-SCF3 | ??CF3 | ??H | ??H | ??EtCO | ??H | ??CH | ??1 |
Table 9
Biological test embodiment 1-at the test of Spodoptera litura larvae
Solvent: 3 weight part dimethyl formamides
Emulsifying agent: 1 weight part polyoxyethylene alkyl phenyl ether
For preparing suitable active agent preparations,, and this mixed solution is diluted with water to prescribed concentration with the solvent that contains above-mentioned amount emulsifying agent of 1 weight part active compound and above-mentioned amount.
Sweet potato (sweet potate) leaf is immersed in the reagent agent that is diluted with water to prescribed concentration, air-dry, and put into the ware that diameter is 9cm.Put into this ware and leave 25 ℃ of homothermic in 10 three prodenia lituras in age (Spodoptera litura) larva indoor.After 2 days and 4 days, add more Rhizoma Dioscoreae esculentae leaf, thereby and after 7 days the number of the dead larva of counting calculate mortality ratio.In this test, every group of test-results is the result's of two wares mean value.
Be numbered 1-1,1-2,1-4,1-6,1-11,1-12,1-13,1-15,1-16,1-17,1-19,1-20,1-21,1-23,1-24,1-25,1-26,1-27,1-28,1-31,1-32,1-34,1-35,1-36,1-38,1-40,141,1-43,1-44,1-46,1-56,1-57,1-58,1-59,1-60,1-61,1-62,1-63,1-90,1-94,1-97,1-98,1-99, the The compounds of this invention of 1-100 and 1-101 demonstrates 100% mortality ratio under the 100ppm activity compound concentration.
Biological test embodiment 2-at the test (spray testing) of Tetranychus urticae
Solvent: 3 weight part dimethyl formamides
Emulsifying agent: 1 weight part polyoxyethylene alkyl phenyl ether
For preparing suitable active agent preparations,, and this mixed solution is diluted with water to prescribed concentration with the solvent that contains above-mentioned amount emulsifying agent of 1 weight part active compound and above-mentioned amount.
The one-tenth mite of 50-100 Tetranychus urticae (Tetranychus urticae) is connected on the leaf that is planted in two leaf phase Kidney beans in the basin that diameter is 6cm.After 1 day, with the active compound of the prescribed concentration of gun spraying capacity through dilute aqueous solution.After the spraying, this basin is deposited 7 days in the greenhouse, and uses following evaluation criteria to calculate acaricidal rate:
| Acaricidal rate | |
| ??100 | All acarids that insert are all dead |
| ??98 | 1-4 acarid survival/breeding |
| ??90 | 5-20 acarid survival/breeding |
| ??60 | Many acarid survival/breedings, but be less than undressed control group, observe some dead volumes |
| ??0 | Do not observe difference with undressed control group |
The The compounds of this invention that is numbered 1-1,1-2,1-6,1-11,1-12,1-13,1-15,1-16,1-17,1-19,1-20,1-21,1-24,1-26,1-27,1-28,1-31,1-33,1-34,1-35,1-36,1-38,1-40,1-41,1-44,1-46,1-57,1-58,1-59,1-61,1-62,1-63,1-90,1-93,1-94,1-99,1-101 and 1-102 demonstrates the acaricidal rate greater than 98 under the 100ppm activity compound concentration.
Biological test embodiment 3-at the test of aulacophora femoralis
Solvent: 3 weight part dimethyl formamides
Emulsifying agent: 1 weight part polyoxyethylene alkyl phenyl ether
For preparing suitable active agent preparations,, and this mixed solution is diluted with water to prescribed concentration with the solvent that contains above-mentioned amount emulsifying agent of 1 weight part active compound and above-mentioned amount.
With the leaf of cucumber be immersed in with above-mentioned test in the prescribed concentration for preparing of identical mode active compound in dilute aqueous solution, air-dry, and put into the plastic cup that contains the black earth of sterilizing.Then 5 two aulacophora femoralises in age (Aulacophora femoralis) larva is put into this cup.After 7 days, thereby the number of counting dead larva calculates mortality ratio.
Be numbered 1-1,1-2,1-6,1-11,1-12,1-13,1-15,1-16,1-17,1-19,1-20,1-21,1-23,1-24,1-26,1-27,1-28,1-31,1-32,1-33,1-34,1-35,1-36,1-38,1-40,1-41,1-44,1-46,1-57,1-58,1-59,1-60,1-61,1-62,1-63,1-93,1-94,1-97,1-98,1-99,1-100,1-101, the The compounds of this invention of 1-102 and 1-106 demonstrates 100% mortality ratio under the 100ppm activity compound concentration.
Biological test embodiment 4-at the test of the black peach aphid with organophosphorus medicament and carbamate medicament resistance
Solvent: 3 weight part dimethyl formamides
Emulsifying agent: 1 weight part polyoxyethylene alkyl phenyl ether
For preparing suitable active agent preparations,, and this mixed solution is diluted with water to prescribed concentration with the solvent that contains above-mentioned amount emulsifying agent of 1 weight part active compound and above-mentioned amount.
It is that every strain rice shoot is inoculated about 30 to 50 on the leaf of the two leaf stage eggplant in the basin of 6cm at diameter that the adult that will have a black peach aphid (Myzus persicae) of organophosphorus medicament and carbamate medicament resistance is connected to cultivation.Inoculate back 1 day, with the gun spraying capacity with above-mentioned test in the prescribed concentration for preparing of identical mode active compound through dilute aqueous solution.After the spraying, this basin was deposited in 28 ℃ greenhouse 7 days, calculated mortality ratio.Repeat this test.
As specific examples, the above-claimed cpd that is numbered 1-31 and 1-61 demonstrates 100% mortality ratio under the activity compound concentration of 500ppm.
Biological test embodiment 5-1-at the test of ctenocephalides felis
Solvent: dimethyl formamide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the above-mentioned solvent of 0.5mL, and this mixed solution is diluted to prescribed concentration with animal blood.
About 10-15 ctenocephalides felis (Ctenocephalides felis) adult is put into a flea special container.To contain and comprise that as above another container of the described blood solution of the compound of preparation covers with laboratory film [PARAFILM (trade mark)].The container that will contain blood is inverted and is placed on this flea special container.This system makes ctenocephalides felis can suck blood in this container.This blood solution is deposited under 37 ℃, and this flea special container is at room temperature deposited.After specific for some time, calculate the mortality ratio of ctenocephalides felis.For this test, it is all dead that 100% mortality ratio means all ctenocephalides felis, and 0% mortality ratio means all ctenocephalides felis and all survives.
In this biological test, compound 1-64 demonstrates the mortality ratio greater than 80% under the 100ppm activity component concentration.
Biological test embodiment-5-2-at the test of ctenocephalides felis
Solvent: methyl-sulphoxide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the 0.5mL solvent, and this dope is diluted to desired concn with ox blood.
The adult (ctenocephalides felis (Ctenocephalides felis)) that about 10-15 head is not sucked blood is put into the flea chamber.Contain the ox blood of compound solution and be placed on top, flea chamber with sealing to pack in the blood chamber of film phonograph seal to the bottom, thereby make flea can suck this blood.The blood chamber is heated to 37 ℃, and this flea chamber is at room temperature deposited.
After the specified time period, determine mortality ratio in %.100% means all fleas all is killed; 0% means and does not have flea to be killed.
In this test, the compound of for example following preparation embodiment demonstrates under the 100ppm rate of application 〉=80% excellent activity:
Embodiment numbers 1-1,1-5,1-6,1-12,1-13,1-15,1-16,1-19,1-20,1-21,1-23,1-24,1-25,1-26,1-27,1-28,1-31,1-33,1-34,1-35,1-36,1-38,1-40,1-41,1-42,1-44,1-46,1-57,1-58,1-59,1-60,1-61,1-63,1-64,1-93,1-94,1-98,1-101,7-1,1-128,1-129,1-131,1-140,2-2.
Biological test embodiment 6-1-at the test (injection) of boophilus microplus
Solvent: dimethyl formamide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the above-mentioned solvent of 0.5mL, and this mixture is diluted with water to prescribed concentration.
The compound solution of as above preparation is injected the belly of 5 female boophilus micropluses of fully sucking blood (Boophilus microplus) adult.Transfer to these boophilus micropluses in the replica ware (replica dish) and in incubator, deposit specific for some time.
After specific for some time, calculate the mortality ratio of boophilus microplus.In this test, it is all dead that 100% mortality ratio means all boophilus micropluses, and 0% mortality ratio means all boophilus micropluses and all survives.
In above-mentioned this biological test, compound 1-64 demonstrates the mortality ratio greater than 80% when the activeconstituents dosage of 20ug/ animal.
Biological test embodiment 6-2-at the test (injection) of boophilus microplus
Solvent: methyl-sulphoxide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the 0.5mL solvent, and this dope is diluted with water to desired concn.
Compound solution is injected the belly of 5 female ticks of being satiated with food (boophilus microplus (Boophilusmicroplus)) adult.Transfer to tick in the replica ware and middle in the controlled environment chamber the cultivation for some time.
After one period fixed time, determine mortality ratio in %.100% to mean all ovum all sterile; 0% means all ovum all can educate.
In this test, the compound of for example following preparation embodiment demonstrates when the rate of application of 20 μ g/ animals 〉=80% excellent activity:
Embodiment numbers 1-1,1-5,1-6,1-12,1-13,1-15,1-16,1-19,1-20,1-21,1-22,1-23,1-24,1-25,1-26,1-27,1-28,1-31,1-32,1-33,1-34,1-35,1-36,1-37,1-38,1-40,1-41,1-42,1-43,1-44,1-46,1-57,1-58,1-59,1-60,1-61,1-63,1-64,1-79,1-93,1-94,1-98,1-99,1-100,1-101,1-102,1-106,1-128,1-129,1-131,1-133,1-140,2-2,2-3,2-4,2-5,2-6,2-46,2-47,2-54,7-1.
Biological test embodiment 7-1-at the test of lucilia cuprina
Solvent: dimethyl formamide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the above-mentioned solvent of 0.5mL, and this mixed solution is diluted with water to prescribed concentration.
Will about 20-30 lucilia cuprina (Lucillia cuprina) larva put into one and contain 1cm
3In the test tube of the compound water solution that broken horseflesh and 0.5mL as above prepare.
After specific for some time, calculate the mortality ratio of lucilia cuprina.For this test, it is all dead that 100% mortality ratio means all lucilia cuprinas, and 0% mortality ratio means all lucilia cuprinas and all survives.
In this biological test, compound 1-64 demonstrates the mortality ratio greater than 80% when the 100ppm activity component concentration.
Biological test embodiment 7-2-at the test of lucilia cuprina
Solvent: methyl-sulphoxide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the 0.5mL solvent, and this dope is diluted with water to desired concn.
Will about 20-30 lucilia cuprina (Lucillia cuprina) larva transfer in the test tube of a water diluent that contains broken horseflesh of 1cm3 and 0.5mL test compound.
After specifying for some time, calculate mortality ratio in %.100% means all death of all larvas; 0% means no larva is killed.
In this test, the compound of for example following preparation embodiment demonstrates when the rate of application of 100ppm 〉=80% excellent activity:
Embodiment numbers 1-1,1-5,1-6,1-12,1-13,1-15,1-16,1-19,1-20,1-21,1-23,1-24,1-25,1-26,1-27,1-28,1-31,1-32,1-33,1-34,1-35,1-36,1-37,1-38,1-40,1-41,1-42,1-43,1-44,1-46,1-57,1-58,1-59,1-60,1-61,1-63,1-64,1-93,1-94,1-98,1-101,1-129,1-131,1-140,2-2,2-5,2-6,2-46,2-47,7-1.
Biological test embodiment 8-1-at the test of housefly
Solvent: dimethyl formamide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the above-mentioned solvent of 0.5mL, and the gained mixed solution is diluted with water to prescribed concentration.
In the preparatory stage, mixture sugared and the as above aqueous solution of the compound of preparation is sucked in the sponge of intended size, and this sponge is put into a test chamber.10 boss fly (Muscadomestica) adults are put into this container, and with the cap covers of this container with perforation.
After specific for some time, calculate the mortality ratio of housefly.In this test, it is all dead that 100% mortality ratio means all houseflies, and 0% mortality ratio means all houseflies and all survives.
In this biological test, compound 1-64 demonstrates the mortality ratio greater than 80% under the 100ppm activity component concentration.
Biological test embodiment 8-2-at the test of housefly
Solvent: methyl-sulphoxide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the 0.5mL solvent, and this dope is diluted with water to desired concn.
Before the test, the mixture of a slice kitchen sponge with sugar and compound solution soaked, and this sponge is put into a container.10 boss flies (Musca domestica) adult is put into this container and uses the closed with covers of boring a hole.
After specifying for some time, determine mortality ratio in %.100% means all houseflies all is killed; 0% means no housefly is killed.
In this test, the compound of for example following preparation embodiment demonstrates when the rate of application of 100ppm 〉=80% excellent activity:
Embodiment numbers 1-1,1-6,1-12,1-13,1-15,1-16,1-19,1-20,1-21,1-23,1-26,1-36,1-38,1-40,1-41 ,-42,1-44,1-46,1-57,1-58,1-59,1-60,1-61,1-63,1-64,1-79,1-94,1-99,1-101,1-129,1-131,1-140,2-5,7-1.
Biological test embodiment 9-at the test (dipping) of boophilus microplus
Solvent: methyl-sulphoxide
For preparing suitable active agent preparations, the 10mg active compound is dissolved in the 0.5mL solvent, and this dope is diluted with water to desired concn.
The female boophilus microplus (Boophilus microplus) that the 8-10 head is satiated with food becomes tick to put into the plastic beaker of perforation and compound water solution dipping 1 minute.This tick is transferred on the filter paper in the plastic pallet.The situation of laying eggs of monitoring zygote after 7 days.
After specifying for some time, determine mortality ratio in %.100% means all tick worms is killed; 0% means no tick worm is killed.
In this test, the compound of for example following preparation embodiment demonstrates when the rate of application of 100ppm 〉=80% excellent activity:
Embodiment numbers 1-4,7-1,1-12,1-13,1-16,1-19,1-20,1-21,1-24,1-27,1-28,1-31,1-33,1-40,1-41,1-42,1-44,1-57,1-58,1-59,1-60,1-63,1-64,1-94,1-99,1-101,1-129,1-131,1-133,1-140.
Biological test embodiment 10-spend the test of tick at Hebrew
Solvent: methyl-sulphoxide
For preparing suitable active agent preparations,, and this dope released to desired concn with contained solvent the solvent of 1 weight part active compound and described amount.
Spend the nymph of tick (Amblyomma hebraeum) to put into the plastic beaker of perforation and Hebrew compound water solution dipping 1 minute.This tick is transferred on the filter paper in the culture dish and in the controlled environment chamber cultivated 42 days.
After specifying for some time, determine mortality ratio in %.100% means all tick worms is killed; 0% means no tick worm is killed.
In this test, the compound of for example following preparation embodiment demonstrates when the rate of application of 100ppm 〉=80% excellent activity:
Embodiment numbers 1-13,1-19,1-20,1-44,1-58,1-59,1-101.
Biological test embodiment 11-at the drug effect of the ctenocephalides felis nominate subspecies (cat flea) on the cat
In the research, when preceding 4 days of processing and 1 day, with about 100 not ctenocephalides felis nominate subspecies (the Ctenocephalides felis felis) adults of feed cat is infected.Ctenocephalides felis is placed on the neck fur of cat.
In research 0 day the time, by the counting cat on one's body the number of this flea check infection rate.The number of record flea alive.
After this flea counted, use the product of being studied that cat is handled.The cat of control group is not handled and as negative control group.The veterinary products studied is carried out single-point (one spot) percutaneous drug delivery with the dose volume of 0.1-0.2ml/kg body weight.Described processing is only carried out 1 time in the time of 0 day in research.Only the cat of health is handled and includes in the research.
When research 1 day and/or 2 days, flea is counted, wherein cat is carried out combing and the record flea number of living.Preserve the gained result.
Weekly, every cat is infected with about 100 ctenocephalides felis adults of not taking food again.Infected again back 1 day and/or 2 days, cat is carried out combing and counts the flea number alive of every cat.Record gained result.
Handling and at weekly 24h to 48h after infecting again, if drug effect can reach＞95%, think that then this activeconstituents height is effective.Drug effect should provide through the time in 3-4 week.
For the calculating of drug effect, use improved Abbott formula:
CG: control group
TG: treatment group
The activeconstituents 1-129 that carries out point type (Spot-on) administration with the dosage of 0.1ml/kg (15mg/kg) has＞95% high-drug-effect ctenocephalides felis nominate subspecies cat flea.
Biological test embodiment 12-at the drug effect of the tick worm (castor bean tick) on the cat
Under study for action, handled preceding 4 days and/or 1 day, make the cat calmness with the binding substances of active ingredient hydrochloric acid ketamine (ketaminhydrochloride) and acetypromazin maleate (acepromazinmaleat).After all cat calmness (after about 10-15 minute), all cats are put into single cage and 50 castor bean ticks (Ixodes ricinus ticks) (25 female and 25 male) are placed on the back fur of cat.Make the about 1h-1.5h of cat sleep and stop its reason hair and remove this tick worm.
Preceding 3 days of research or when studying 0 day, cat is placed on the check-out console to check the infection rate of tick worm.Zone between the sidepiece of emphasis inspection head, ear, eye, neck and health and the neighboring area of veutro portion and toe.The number of the tick worm alive of being satiated with food that counting and record adhere to.Remove dead tick worm.
When studying 0 day,, it is handled behind the tick worm counting.The cat of control group is not handled and as negative control group.The veterinary products single-point of being studied is administered to the skin of head base portion.Described processing was only carried out once in the time of 0 day.Only the cat of clinical health is included in the research.
The 1st day and/or 2 days of research the tick worm counted, and counting and record survival or the dead tick borer population order that adheres to.At the 2nd day, remove all survivals and dead tick worm.
Weekly, every cat is infected with 50 castor bean ticks (25 female and 25 male), and the tick worm is counted infecting back 1 day and/or 2 days again.And counting and record survival and dead adhere to the tick worm.Infected again back 2 days, and removed all tick worms.
Handling and at weekly 48h after infecting again, if drug effect can reach＞90%, think that then this activeconstituents height is effective.Drug effect should provide through the time in 3-4 week.
For the calculating of drug effect, use improved Abbott formula:
CG: control group
TG: treatment group
The activeconstituents 1-129 that carries out the point type administration with the dosage of 0.1ml/kg (15mg/kg) has＞90% high-drug-effect castor bean tick.
Example of formulations 1 (granule)
In the mixture that contains 10 parts of The compounds of this invention (numbering 1-1), 30 parts of wilkinites (polynite), 58 parts of talcums and 2 parts of Sulfite lignin; add 25 parts of water; with this mixture thorough mixing and by Squeezinggranulator through the granulation of 10-40 sieve mesh; dry under 40-50 ℃ temperature, obtain granule.
Example of formulations 2 (granule)
The clay mineral grain of 95 (95) parts of size distribution in 0.2 to 2mm scope put into impeller.In the mixing tank rotary course, (numbering 1-2) sprays with liquid diluent with 5 parts of The compounds of this invention, and be wetting even, and dry under 40-50 ℃ temperature, obtains granule.
Example of formulations 3 (missible oil)
30 (30) parts of The compounds of this invention (numbering 1-13), 55 parts of dimethylbenzene, 8 parts of polyoxyethylene alkyl phenyl ethers and 7 parts of alkyl benzene calcium sulfonates are mixed and stir, obtain a kind of missible oil.
Example of formulations 4 (wettable powder)
Ten five (15) parts of The compounds of this invention (numbering 1-13), 80 parts of white carbon(ink)s (hydration amorphous silicon oxide fine powder) and the mixture of powdered clay (1: 5), 2 parts of sodium alkyl benzene sulfonates and 3 parts of sodium alkyl naphthalene sulfonate-formalin condensess are mixed together, pulverize and mixing, obtain a kind of wettable powder.
Example of formulations 5 (water dispersible granules)
20 (20) parts of The compounds of this invention (numbering 1-1), 30 parts of sodium lignosulfonates, 15 parts of wilkinites and 35 parts of incinerating diatomite are carried out thorough mixing, and after adding entry, extrude with the sieve of 0.3mm, and dry, obtain a kind of water dispersible granules.
Industrial applicability:
New aryl isoxazoline derivatives of the present invention has good killing insect and kill the acarid activity as insecticide and/or acaricide, and is as shown here.
Claims (10)
1. the aryl isoxazoline derivatives of following formula:
Wherein
A represents C or N;
R represents alkyl or haloalkyl;
X can be identical or different, and it represents halogen, haloalkyl, nitro, alkyl, alkoxyl group, cyano group, halogenated alkoxy, alkyl sulphinyl, alkyl sulfenyl, alkyl sulphonyl, haloalkyl sulfinyl, haloalkyl sulfenyl, halogenated alkyl sulfonyl, amino, amido, alkoxycarbonyl amino, halogenated alkyl carbonyl amino, halo alkoxy carbonyl amino, alkyl sulfonyl-amino, halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Y can be identical or different, and it represents halogen, haloalkyl, nitro, alkyl, alkoxyl group, cyano group, halogenated alkoxy, alkyl sulphinyl, alkyl sulfenyl, alkyl sulphonyl, haloalkyl sulfinyl, haloalkyl sulfenyl, halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, amido, alkoxycarbonyl amino, halogenated alkyl carbonyl amino, halo alkoxy carbonyl amino, alkyl sulfonyl-amino or halogenated alkyl sulfonyl amino; Or two adjacent Y form an optional substituted ring with the carbon atom that they connected;
L represents 0,1,2,3,4 or 5;
M represents 0,1,2,3 or 4;
N represents 1,2 or 3;
R
1And R
2Represent hydrogen, alkyl, optional substituted cycloalkyl, haloalkyl, cyano group, alkoxy carbonyl, alkenyl or alkynyl, perhaps R independently of one another
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, alkyl, optional substituted cycloalkyl, haloalkyl, cyano group, thiazolinyl, alkynyl, alkyl-carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, alkyl-carbonyl, alkylthio carbonyl, halogenated alkyl carbonyl, halogenated alkylthio carbonyl, alkyl amino-carbonyl, alkylamino thiocarbonyl, dialkyl amino carbonyl, dialkyl amido thiocarbonyl, alkoxy amino carbonyl, alkoxyl group thiocarbonyl, alkoxy amino thiocarbonyl, alkoxy carbonyl, thio alkoxy carbonyl, thio alkoxy thiocarbonyl,
Alkyl sulphonyl or halogenated alkyl sulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form 3 yuan to 6 yuan rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and wherein the carbon atom of formation ring can be replaced by ketone group or thioketones base.
2. the compound of claim 1, wherein
A represents C or N;
R represents C
1-6Alkyl or C
1-6Haloalkyl;
X can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, amino, C
1-6Alkyl-carbonyl, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino, C
1-6Halogenated alkyl sulfonyl amino, hydroxyl or sulfydryl;
Y can be identical or different, and it represents halogen, C
1-6Haloalkyl, nitro, C
1-6Alkyl, C
1-6Alkoxyl group, cyano group, C
1-6Halogenated alkoxy, C
1-6Alkyl sulphinyl, C
1-6Alkyl sulfenyl, C
1-6Alkyl sulphonyl, C
1-6Haloalkyl sulfinyl, C
1-6Haloalkyl sulfenyl, C
1-6Halogenated alkyl sulfonyl, hydroxyl, sulfydryl, amino, C
1-4Alkyl-carbonyl-amino, benzoyl-amido, C
1-6Alkoxycarbonyl amino, C
1-6Halogenated alkyl carbonyl amino, C
1-6Halo alkoxy carbonyl amino, C
1-6Alkyl sulfonyl-amino or C
1-6Halogenated alkyl sulfonyl amino; Or two adjacent Y form an optional substituted benzene with the carbon atom that they connected;
L represents 0,1,2 or 3;
M represents 0,1 or 2;
N represents 1;
R
1And R
2Represent hydrogen, C independently of one another
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
1-6Alkoxy carbonyl, C
2-4Thiazolinyl or C
2-4Alkynyl, perhaps R
1And R
2Represent C together
2-5Alkylidene group;
R
3Represent hydrogen, C
1-6Alkyl, optional substituted C
3-7Cycloalkyl, C
1-6Haloalkyl, cyano group, C
2-4Thiazolinyl, C
2-4Alkynyl, C
1-6Alkyl-carbonyl or CH
2-R
5, R wherein
5The optional substituted phenyl of representative or an optional substituted heterocyclic radical; And
R
4Represent formyl radical, cyano group, C
1-6Alkyl-carbonyl, C
1-6Alkylthio carbonyl, C
1-6Halogenated alkyl carbonyl, C
1-6Halogenated alkylthio carbonyl, C
1-6Alkyl amino-carbonyl, C
1-6Alkylamino thiocarbonyl, C
2-8(sum of carbon) dialkyl amino carbonyl, C
2-8(sum of carbon) dialkyl amido thiocarbonyl, C
1-6Alkoxy amino carbonyl, C
1-6Alkoxyl group thiocarbonyl, C
1-6Alkoxy amino thiocarbonyl, C
1-6Alkoxy carbonyl, sulfo--C
1-6Alkoxy carbonyl, sulfo--C
1-6The alkoxyl group thiocarbonyl,
C
1-6Alkyl sulphonyl or C
1-6Haloalkyl-alkylsulfonyl, wherein R
5Definition as above; Or
R
3And R
4Can form one 4 yuan or 5 yuan of rings with the nitrogen-atoms that they connected, this ring also can contain 1 or 2 heteroatoms that is selected from N, O or S except that the N atom, and wherein the carbon atom of formation ring can be replaced by ketone group or thioketones base.
3. insect-killing composition, it contains the compound of at least a claim 1 or 2.
4. be used to be administered to the pharmaceutical composition of animal, it contains the compound of at least a claim 1 or 2.
5. the method for control animal nuisance is characterized in that the aryl isoxazoline derivatives of the formula (I) of claim 1 or 2 is applied to animal nuisance and/or its habitat.
6. be used to prevent and treat the aryl isoxazoline derivatives of claim 1 or 2 the formula (I) of pest.
7. the aryl isoxazoline derivatives of claim 1 or 2 formula (I) purposes that is used to prevent and treat the animal nuisance.
8. the aryl isoxazoline derivatives of claim 1 or 2 formula (I) is used to prepare the purposes of the pharmaceutical composition that is used to prevent and treat the animal nuisance.
9. the aryl isoxazoline derivatives of claim 1 or 2 formula (I) is used to handle the purposes of seed.
10. the aryl isoxazoline derivatives of claim 1 or 2 formula (I) is used to handle the purposes of transgenic plant.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007102395A JP2008260691A (en) | 2007-04-10 | 2007-04-10 | Insecticidal arylisoxazoline derivative |
| JP102395/2007 | 2007-04-10 | ||
| EP07123793 | 2007-12-20 | ||
| EP07123793.7 | 2007-12-20 | ||
| PCT/EP2008/002474 WO2008122375A2 (en) | 2007-04-10 | 2008-03-28 | Insecticidal aryl isoxazoline derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101652354A true CN101652354A (en) | 2010-02-17 |
| CN101652354B CN101652354B (en) | 2014-06-18 |
Family
ID=39983451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880011571.8A Expired - Fee Related CN101652354B (en) | 2007-04-10 | 2008-03-28 | Insecticidal aryl isoxazoline derivatives |
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| Country | Link |
|---|---|
| JP (1) | JP2008260691A (en) |
| CN (1) | CN101652354B (en) |
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| WO2007105814A1 (en) * | 2006-03-10 | 2007-09-20 | Nissan Chemical Industries, Ltd. | Substituted isoxazoline compound and pest control agent |
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| Publication number | Publication date |
|---|---|
| CN101652354B (en) | 2014-06-18 |
| JP2008260691A (en) | 2008-10-30 |
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