• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Enantiomers of Formula 1 in free or salt form; Methods of making and using these enantiomers; Pesticides wherein the active ingredient is selected from these enantiomers; And methods of making and using these compositions are described. <Formula 1> Wherein X, Y, Z, R 1 , R 2 , m and n are as defined in claim 1.
    公开号:KR20020008387A
    申请号:KR1020017012185
    申请日:2000-03-24
    公开日:2002-01-30
    发明作者:올리비에르 프로엘리히；자끄 보비에르
    申请人:한스 루돌프 하우스, 헨리테 브룬너, 베아트리체 귄터；노파르티스 아게；
    IPC主号:
    专利说明:

    2,4-disubstituted oxazoline insecticide as pure enantiomer {Pesticidal Enantiomer-Pure 2,4-Disubstituted Oxazolines}
    [1] Subjects of the present invention are enantiomers of formula (I) in free or salt form, respectively; Methods of making and using these compounds and salts thereof; Pesticides in which the active ingredient is selected from these compounds; Methods of making and using these compositions; And intermediates in free or salt form for the preparation of these compounds in free or salt form.
    [2]
    [3] Where
    [4] X and Y are each independently hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkyl Thio, C 1 -C 4 -haloalkylthio, cyano-C 1 -C 4 -alkyl, cyano-C 1 -C 4 -haloalkyl, cyano-C 1 -C 4 -alkoxy, cyano-C 1 -C 4 -haloalkoxy, cyano-C 1 -C 4 -alkylthio, cyano-C 1 -C 4 -haloalkylthio, halogen, amino, cyano or nitro;
    [5] Z is hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy or di (C 1 -C 4 -alkyl) amino;
    [6] R 1 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkylthio, cyano-C 1 -C 4 -alkyl, cyano-C 1 -C 4 -haloalkyl, cyano-C 1 -C 4 -alkoxy, cyano-C 1 -C 4 -halo Alkoxy, cyano-C 1 -C 4 -alkylthio, cyano-C 1 -C 4 -haloalkylthio, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 - alkenyloxy, C 2 -C 6 - haloalkyl alkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 2 -C 6 - alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 3 -C 8 -cycloalkyl, C 3 -C 8 -halocycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, C 3 -C 8 -halo cycloalkyl, -C 1 -C 4 - alkyl, OC (O) R 3, or halogen;
    [7] R 2 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkylthio or halogen;
    [8] R 3 is C 1 -C 4 - alkyl, C 1 -C 4 - alkoxy, C 2 -C 6 - alkenyl, C 2 -C 6 - alkenyloxy, C 2 -C 6 - alkynyl, C 2 - C 6 - alkynyloxy, C 3 -C 8 - cycloalkyl, C 3 -C 8 - cycloalkyl-oxy, C 3 -C 8 - halocycloalkyl -C 1 -C 4 - alkyl, C 3 -C 8 - Halocycloalkyl-C 1 -C 4 -alkyloxy, N (R 4 R 5 ), unsubstituted phenyl or mono to penta-substituted phenyl, wherein the substituents are C 1 -C 4 -alkyl, C 1 -C 4 -Haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkylthio, halogen, cyano and nitro Selected from);
    [9] R 4 is hydrogen or C 1 -C 4 -alkyl;
    [10] R 5 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 8 -cycloalkyl, C 3 -C 8 -halocycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, C 3 -C 8 -halocycloalkyl-C 1 -C 4 -alkyl, unsubstituted or mono to penta-substituted phenyl, unsubstituted or mono to penta-substituted phenyl-C 1 -C 4 -alkyl, wherein the substituents are each independently selected from the group comprising C 1 -C 4 -alkyl;
    [11] m and n are each independently 0, 1 or 2, and when m or n is 2, R 1 or R 2 may be the same or different from each other.
    [12] Enantiomeric mixtures of the general formula (1) are disclosed in the literature for example in the field of crop protection, for example in European Patent No. 0,432,661, European Patent No. 0,696,584 and German Patent No. 19,523,388. Despite the good efficacy of the mixtures, there is a need to provide compounds with improved pest control properties, since the properties of known enantiomeric mixtures when used as pesticides are not always completely satisfactory for all pests. It is solved according to the invention by the preparation of substantially pure enantiomers of the formula (1).
    [13] Surprisingly, the necessity can be very satisfied with the use of pure enantiomers of the formula (1) presented according to the invention. Each enantiomer according to the invention (hereinafter referred to as "A") not only shows higher potency against pests than enantiomeric mixtures, but in some cases is unpredictably lower in treated animals and plants than enantiomeric mixtures. While other tolerated, other enantiomers (hereinafter referred to as "B") show no or much lower efficacy against pests. There is a wider safety limit for the user with the increased efficacy of enantiomer A, so that if necessary, it is difficult to combat, for example, by increasing the amount of active ingredient without having to worry that the treated animals or plants will be harmed at the same time. It can effectively control pests. Due to the improved properties of enantiomer A, there is a tremendous interest in mixing partners for incorporation with other active substances, for example to broaden the activity spectrum. In the mixture, the two partners can be used in substantially low amounts and any adverse interaction of the inert enantiomer B with the partner in the mixture is excluded. Moreover, from the point of view of successful resistance management, the use of pure enantiomer A is preferred because the permanent presence of inert enantiomer B in an amount lower than the lethal dose can significantly accelerate the development of resistance of the target pest.
    [14] In addition, the improved crystallization behavior and better formulation properties of the enantiomers of Formula 1 are noteworthy.
    [15] Typically, Enantiomer A of Formula 1 shows negative optical rotation in polar Na D light (589 nm) of a sodium vapor lamp. However, enantiomer A showing positive optical rotation should be excluded. In any case, the much more active enantiomer is A.
    [16] Therefore, the present invention provides the enantiomer A of formula 1 as an insecticide for controlling insecticides, in particular insects and other pests belonging to the tree of Acarina.
    [17] Preference is given to enantiomers having a purity of at least 95%.
    [18] Compounds of formula (1) may form salts, such as acid addition salts. These salts include strong organic acids such as mineral acids (eg sulfuric acid, phosphoric acid or hydrohalic acid); Strong organic carboxylic acids such as optionally substituted C 1 -C 4 -alkane-carboxylic acids such as acetic acid, optionally unsubstituted dicarboxylic acids such as oxalic acid, malonic acid, maleic acid , Fumaric acid or phthalic acid), hydroxycarboxylic acids (eg, ascorbic acid, lactic acid, maleic acid, tartaric acid, citric acid, or benzoic acid); Or organic sulfuric acid such as C 1 -C 4 -alkanesulfonic acid or, optionally, for example, arylsulfonic acid (eg methanesulfonic acid or p-toluenesulfonic acid) substituted with halogen. Glass form is preferred. Preferred among the salts of the enantiomers of formula (1) are agrochemically beneficial salts.
    [19] Before and after, it is understood that the enantiomers of formula (1) and salts thereof optionally also include the free enantiomers of formula (1) and the corresponding salts.
    [20] Unless otherwise specified, the meanings of general terms used before and after are as follows.
    [21] Halogen atoms considered as substituents of halogen-alkyl and halogen-alkoxy are fluorine, chlorine, bromine and iodine, with fluorine and chlorine being preferred.
    [22] Unless contradictoryly defined, the carbon-containing groups and compounds preferably contain 1 to 4, in particular 1 or 2, carbon atoms.
    [23] Alkyl as the group itself, and other groups and compounds, such as alkyl as structural elements of alkoxy, halogen-alkyl or halogen-alkoxy, are each considering the particular number of carbon atoms in that group or compound being straight or branched chain. In the case, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or one of the respective isomers thereof. Preferred alkyl groups are C 1 -C 2 -alkyl groups, in particular methyl groups.
    [24] Cycloalkyl as the group itself, and cycloalkyl as the structural element of other groups and compounds, such as halocycloalkyl, cycloalkoxy and cycloalkylthio, are in each case taking full account of the particular number of carbon atoms in that group or compound. , Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.
    [25] Alkenyl as the group itself, and alkenyl as the structural element of other groups and compounds, such as alkenyloxy, take full account of the specific number of carbon atoms and the number of conjugated or separated straight chain double bonds in the group or compound. In each case, for example, allyl, 2-butenyl, 3-pentenyl, 1-hexenyl, 1-heptenyl, 1,3-hexadienyl, 1,3-octadienyl or branched (eg , Isopropenyl, isobutenyl, isoprenyl, tert-pentenyl, isohexenyl, isoheptenyl or isooctenyl).
    [26] Alkynyl as the group itself, and other groups and compounds, such as alkynyl as the structural element of alkynyloxy, take full account of the specific number of carbon atoms and the number of conjugated or separated straight chain double bonds in the group or compound. In each case, for example, propargyl, 2-butynyl, 3-pentynyl, 1-hexynyl, 1-heptinyl, 3-hexen-1-ynyl, 1,5-heptadiene-3-ynyl, Or branched (eg, 3-methylbut-1-ynyl, 4-ethylpent-1-ynyl, 4-methylhex-2-ynyl or 2-methylhept-3-ynyl).
    [27] Halogen-substituted groups, ie halogen-alkyl and halogen-alkoxy, may be partially halogenated or overhalogenated. Examples of halogen-alkyl as the group itself, and halogen-alkyl as structural element of other groups and compounds such as halogen-alkoxy are methyl mono- to tri-substituted with fluorine, chlorine and / or bromine such as CH 2 F or CF 3 ; Ethyl mono- to penta-substituted with fluorine, chlorine and / or bromine such as CH 2 CH 2 F, CH 2 CF 3 , CF 2 CF 3 , CF 2 CCl 3 , CF 2 CHCl 2 , CF 2 CHF 2 , CF 2 CFCl 2 , CF 2 CHBr 2 , CF 2 CHCIF, CF 2 CHBrF or CCIFCHCIF; And propyl or isopropyl mono- to hepta-substituted with fluorine, chlorine and / or bromine, such as CH 2 CHBrCH 2 Br, CF 2 CHFCF 3 , CH 2 CF 2 CF 3 or CH (CF 3 ) 2 .
    [28] Enantiomers having a purity of about 95-100%, preferably 98-100% are preferred within the scope of the present invention. The preferred enantiomer is
    [29] (1) an enantiomer of Formula 1, wherein X and Y are each independently chlorine or fluorine, preferably fluorine, and Z is hydrogen;
    [30] (2) R 1 is C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, C 1 -C 2 -alkylthio, C 1 -C 2 -haloalkylthio, cyano-C 1 -C 2 -alkyl, cyano-C 1 -C 2 -haloalkyl, cyano-C 1 -C 2 -alkoxy, cyano-C 1 -C 2 -haloalkoxy, cyano-C 1 -C 2 -alkylthio or cyano-C 1 -C 2 -haloalkylthio, preferably methyl, halomethyl, halomethoxy, halomethylthio, cyanohalo Enantiomer of Formula 1, which is methyl or cyanomethyl, most preferably methyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, cyanomethyl or cyanodifluoromethyl;
    [31] (3) an enantiomer of Formula 1, wherein R 2 is hydrogen, C 1 -C 2 -alkyl, C 1 -C 2 -alkoxy or halogen, preferably hydrogen, methyl or halogen, most preferably hydrogen;
    [32] (4) an enantiomer of formula (1) wherein m is 1 or 2, preferably 1;
    [33] (5) enantiomers of formula (1) wherein n is 0 or 1, preferably 0;
    [34] (6) R 1 is C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, C 1 -C 2 -alkylthio, C 1 -C 2 -haloalkylthio, cyano-C 1 -C 2 -alkyl, cyano-C 1 -C 2 -haloalkyl, cyano-C 1 -C 2 -alkoxy, cyano-C 1 -C 2 -haloalkoxy, cyano-C 1 -C 2 -alkylthio or cyano-C 1 -C 2 -haloalkylthio, R 2 is hydrogen, C 1 -C 2 -alkyl, C 1 -C 2- Enantiomers of formula (I) wherein alkoxy or halogen is m or 1 or 2 and n is 0 or 1;
    [35] (7) R 1 is methyl, halomethyl, halomethoxy, halomethylthio, cyanohalomethyl or cyanomethyl, R 2 is hydrogen, methyl or halogen, m is 1, n is 0 or 1 Enantiomer of Formula 1; And
    [36] (8) Enantiomer of Formula 1, wherein R 1 is methyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, cyanomethyl or cyanodifluoromethyl, R 2 is hydrogen, and m is 1 to be.
    [37] Particular preference is given to the following enantiomers of formula (I):
    [38] 2- (2,6-difluorophenyl) -4- (4'-trifluoromethylbiphenyl-4-yl) -4,5-dihydrooxazole;
    [39] 2- (2,6-difluorophenyl) -4- (4'-methylbiphenyl-4-yl) -4,5-dihydrooxazole;
    [40] 2- (2,6-difluorophenyl) -4- (4'-trifluoromethoxybiphenyl-4-yl) -4,5-dihydrooxazole;
    [41] 2- (2,6-difluorophenyl) -4- (4'-difluoromethoxybiphenyl-4-yl) -4,5-dihydrooxazole;
    [42] 2- (2,6-difluorophenyl) -4- (4'-cyanodifluoromethoxybiphenyl-4-yl) -4,5-dihydrooxazole;
    [43] 2- (2,6-difluorophenyl) -4- (4'-trifluoromethylthiobiphenyl-4-yl) -4,5-dihydrooxazole;
    [44] 2- (2,6-difluorophenyl) -4- (4 '-{1,1,2,2-tetrafluoroethoxy} -biphenyl-4-yl) -4,5-dihydrooxa Sol; And
    [45] 2- (2-chloro-6-fluorophenyl) -4- (4'-trifluoromethoxybiphenyl-4-yl) -4,5-dihydrooxazole.
    [46] Enantiomers of formula (1) according to the present invention can be obtained from known enantiomeric mixtures using methods suitable for separating enantiomers. The method is, for example, derivatization with a defined optically active adjuvant as well as physical methods such as fractional crystallization or chromatography on chiral stationary phases, whereby the enantiomeric pairs can be separated by this separation method. Pure optical enantiomers are then obtained from the isolated enantiomeric derivatives by cleavage of the adjuvant. Another method of obtaining enantiomers from racemates is optionally specific and stereoselective from optically active starting materials.
    [47] The inventors have used enantiomers using chiral stationary phase column chromatography using an alcohol in which the enantiomer of Formula 1 is an organic solvent or solvent mixture, preferably an alcohol mixed with a hydrocarbon, most preferably ethanol or isopropanol and hexane. It was found that it is obtained by separating the mixture.
    [48] The inventors surprisingly find that not only the enantiomer of Formula 1 can be used for plant protection, but also for the enantiomeric mixture, it is very suitable for the prevention and cure of ectoparasites and internal parasites in humans and preferably livestock and pets. Said.
    [49] Unexpectedly, the enantiomers A and B of the formula (1) according to the invention have been found not only slightly different in their pesticidal action but also exhibit completely different bactericidal properties. Enantiomer A exhibits 100 to 1000 times more activity than B, and the activity of B is not a significant commercial value. The activity of B is not biologically suitable because too many parasites survive when using B. In addition, B should not be used because it may induce resistance. In conclusion, this means that the enantiomeric mixtures and enantiomeric B activities, except enantiomer A, are not biologically suitable. In addition, the resistance of A is much higher than that of B. This makes it possible to obtain the same activity as the activity with the enantiomeric mixture using low amounts of the active ingredient, and also increased resistance makes it possible to use high amounts of the active ingredient to combat it without harming the host plant or animal. It can effectively control difficult pests.
    [50] Examples of animal pests include Lepidoptera, such as Acleris spp., Adoxophyes spp., Aegeria spp., And Agrotis spp. .), Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyrotaenia spp. ), Autographa spp., Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp. Chorastoneura spp., Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleolis spp. Coleophora spp., Crocidolomia binotalis, Cryptoprevia Cryptophlebialeucotreta, Cydia spp., Diatraea spp., Diparopsis castanea, Earias spp., Ephestia spp. .), Eucosma spp., Eupoecilia ambiguella, Euprotis spp., Euxoa spp., Grapholita spp. .), Hedia nubiferana, Heliothis (Helicoverpa) spp.], Hellula undalis, Hyphantria cunea, Keiferia lycopersicella, Leucoptera scitella, Litocollethis spp., Lobesia botrana, Lymantria spp., Lyonea spp. Lyonetia spp., Malacosoma spp., Mamestra brassi cae), Manduca sexta, Opperhtera spp., Ostrinia nubilalis, Pammene spp., Pandemis spp., Panol Panislis flammea, Pectinophora gossypiella, Phthorimaea operculella, Pieris rapae, Pieris spp., Fluis spp. Plutella xylostella, Prays spp., Scirpophaga spp., Sesameia spp., Sparganothis spp., Spordorf Spodoptera spp., Synanthone spp., Thaumetopoea spp., Tortrix spp., Tricoplusia ni, and Jobnomeuta genus (Yponomeuta spp.); Coleoptera, such as, for example, Agriotes spp., Antonomus spp., Atomaria linearis, Chatocnema tibialis, Cosmopolites Cosmopolites spp., Curculio spp., Dermestes spp., Diabrotica spp., Epilachna spp., Elemnus spp. Eremnus spp.), Leptinotarsa decemlineata, Lysorhoptrus spp., Melonta spp., Orycaephilus spp. Otiorhynchus spp., Phlyctinus spp., Popillia spp., Psylliodes spp., Rhizopertha spp., Scarabdae (Scarabeidae), Sitophilus spp., Sitotroga spp., Tenebrio o spp.), Tribolium spp. and Troguderma spp .; Orthoptera, for example, Blata spp., Blatella spp., Gryllotalpa spp., Leucophaea maderae, Lucusta genus (Locusta spp.), Periplaneta spp. And Schistocerca spp .; Isoptera, such as Reticulitermes spp .; Psocoptera, such as the genus Liposcelis spp .; Anoplura, such as, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. And Phyloxera spp .; Malallophaga, such as, for example, Damalinia spp., Trichodectes spp., And Bovicola spp .; Thysanoptera, such as Frankliniella spp., Hercinothrips spp., Taeniothrips spp., Tripps palmi , Tripps tabaci and Scirtothrips aurantii; Heteroptera such as Cimex spp., Distantiella theobroma, Dysdercus spp., Euchistus spp., Yurigaster Genus (Eurygaster spp.), Leptocorisa spp., Nezara spp., Pisma spp., Rhodnius spp., Salbergella singularis (Sahlbergella singularis), Scottinophara spp. And Triatoma spp .; Homoptera, such as Aleurothrixus floccosus, Aleirodes brassicae, Aonidiella spp., Aphididae, Apis spp., Aspidiotus spp., Bemisia tabaci, Ceroplaster spp., Chrysomphalus aonidium, Cresom Chalsomphalus dictyospermi, Cocus hesperidum, Empoasca spp., Eriosomalarigerum, Erythroneura spp., Gascardia Genus (Gascardia spp.), Laodelphax spp., Lecanium comi, Lepidosaphes spp., Macrosiphus spp., Mycose (Myzus spp.), genus Nehoteticx spp., nilaparvata genus (Nilaparvata spp.), Paratoria spp., Pemphigus spp., Planococcus spp., Pseudaulacaspis spp., Pseudoulacus spp. Pseudococcus spp., Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Rhopalosiphum spp., Cycetia genus ( Saissetia spp.), Scaphoideus spp., Schizaphis spp., Sitobion spp., Triareurodes vaporariorum, Trioza erythr Trioza erytreae and Unaspis citri; Hymenoptera such as Acromyrmex, Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpi Gilpinia polytoma, Hoplocampa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Solenopsis Genus (Solenopsis spp.) And Vespa spp .; Diptera, such as Aedes spp., Antherigona soccata, Bibio hortulanus, Califora erythrocephala, Ceratitis genus (Ceratitis spp.), Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Dermatobia spp.), Drosophila melanogaster, Fannia spp., Gastrophilus spp., Glossina spp., Haematobia spp. .), Hypoderma spp., Hypobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp. , Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Phe Mia Hiyosquiami (Pegomyia hyoscyami), Phorbia spp., Rhagoletis pomonella, Sciara spp., Stomoxys spp., Tabanus ( Tabanus spp.), Genus Taniaa spp. And Tipula spp .; Siphonaptera, such as Ceratophyllus spp., Xenopsylla cheopis, Ctenocephalides felis, Pulex spp. And Stenoce Cidenocephalides canis; Thisanura, such as Lepisma saccharina; And Acarina, such as, for example, Acarus siro, Aceria sheldoni, Aculus schlechtendali, Amblyomma spp., Argas genus ( Argas spp.), Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Calipitrimerus spp., Coryoptes Genus (Chorioptes spp.), Dermanyssus gallinae, Dermatophagoides spp., Dermacentor spp., Eotetranychus carpini, Eri Eriophyes spp., Haemaphysalis spp., Hyalomma spp., Ixodes spp., Miyobia spp., Miyocotes Myocoptes spp.), Olygonychus pratensis, Ornitodorus genus (Ornithodoros spp.), Panonicus spp., Phyllocoptruta oleivora, Polyphagotarsonemus latus, Psorergates spp. Psoroptes spp., Ripicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Tarsonemus spp., And Tarsonemus spp. Tetranychus spp., Acarapis woodi, Cheylettiella parasitivorax, Cytodites nudus, Demodex spp., Kemidoido Knemidocoptes mutans, Otodectes cynotis, Varroa jacobsoni; Nematodes such as Filariidae, Setariidae, Haemonchus, Trichostrongylus, Ostertagia, Nematodyrus (Nematodirus), Cooperia, Ascaris, Bunostumum, Oesophagostonum, Cabertia, Tricuris, especially Tricuris Bullicus (Trichuris vulpis), Strongilus, Trichonema, Dittyocaulus, Capillaria, Strongiloides, Heterakis, Toxocara, in particular Toxocara canis, Ascariadia, Oxyuris, Ancylostoma, especially Ancylostoma caninum, Uncinaria (Uncinaria), Toxascaris and Paracharis (P arascaris); Dirofilaria, especially Dirofilaria immitis (heartworm).
    [51] The life cycles of various parasites that can infect humans or animals are known to be very complex, which makes it very difficult to control them. For example, ticks can live in a single host or in multiple hosts. They attach themselves to the host animal and eat the blood of the host animal.
    [52] Females detach from the host animal when congested and subsequently lay a number of eggs at protected sites in the surrounding environment. The developing larva looks for a new host animal, which develops into an adult through the larval stage in the new host animal, and the adult eats blood until it is congested. Some species live on the blood of two hosts during their life cycle, and some live on the blood of three hosts.
    [53] Economically important ticks are Amblyomma, Boophilus, Hyaloma, Ixodes, Rhipicephalus and Dermacentor, in particular Bopilus microfluid Mites belonging to the genus Boophilus microplus and B. annulatus, most preferably B. microplus. These mites transmit a number of diseases that can affect humans and animals. Commonly transmitted diseases are bacterial diseases, protozoa diseases, rickettsian diseases and viral diseases. Pathogens of these diseases are particularly transmitted by ticks that feed on the blood of one or more hosts. These diseases can lead to weakness and even death of the host animal. In most cases, the disease results in economically significant damage, such as a decrease in meat value of livestock, damage to usable skin or a decrease in milk production.
    [54] The tick species is usually controlled by treating the animal infected with the anti-mite active composition, ie as a therapeutic means, depending on the type of infection involved. However, for example, the occurrence of ticks in pastures mainly depends on seasonal climatic conditions, and the final infection of the host animal itself depends on the host animal's resistance to ticks. This means that the prevention of ticks is difficult and time-consuming, because the infection by parasites and the resistance of animals to parasites are difficult to measure. Moreover, if the prevention of parasites is to be prevented, additional problems arise because long-term monitoring of possible infections is necessary. The control of parasites is usually not of primary concern, since at the time of the start of control often significant damage has already occurred.
    [55] In addition, because of the complex survival cycle of fleas, none of the known methods of controlling these parasites are entirely satisfactory, especially since most known control methods focus on administering the active ingredient to be present at various stages of fleas. to be. However, this method is very complicated and often unreliable because of the various stages of flea development that respond to a wide variety of materials.
    [56] Flea infections in animals, particularly dogs and cats, have a detrimental effect not only on the animals to be treated but also on animal breeders.
    [57] These adverse effects can cause, for example, local inflammation, demanding pruritus or even allergies and often lead to severe scratches. In addition, flea-infected animals are always at risk of being infected with the genus Dipylidium spp. (Ie, tapeworms, tapeworms).
    [58] Surprisingly, the inventors have optionally administered isomer A of Formula 1 in certain forms, in addition to one or more other substances that enhance the effect, such as metoprene, hydroprene, dicyclanyl, cioate or salts thereof, such as It has been found that topical administration (particularly systemic administration) can remove the ectoparasite very quickly and completely, thereby blocking the complicated developmental cycle of the parasite and at the same time achieving efficient control of the internal parasite. These compositions can exert an excellent antiparasitic effect even when administered to the host animal systemically, ie orally, parenterally, subcutaneously, intramuscularly or intravenously. Due to the present invention, selective sporadic administration of these compounds makes it possible to block in a simple manner the repetitive cycle in which host animals are continually reinfected with various parasites and to continuously eradicate the parasites. Parasites can no longer harm host animals because they die, block replication, do not progress to childhood, and / or block growth.
    [59] Accordingly, another preferred object of the present invention comprises oral and parenteral administration to a host animal, or the use of an implant, wherein the composition contains an effective amount of at least one compound of formula 1 or a veterinary acceptable salt thereof. A method for controlling parasites in livestock, pets and animals.
    [60] Essential to the present invention is the fact that the composition of the present invention is administered in such a way that the active ingredient contained in the composition is present in a sufficient amount in the blood of the host animal so that it can be thought of as an internal parasite, an external parasite, and a vector for the transmission of an internal parasite. Ingestion by other parasites prevents eggs and / or hatched larvae from the parasites of the adult phase from developing.
    [61] This is accomplished by other forms of administration, for example by oral administration of a composition of the invention comprising the active ingredient. In this case, the preparations, for example, powders, tablets, granules, capsules, emulsions, foams, microencapsulated forms, do not need to be administered directly to the animal as already mentioned and conveniently with the animal's food. Can be mixed. Of course, all compositions to be administered orally may contain other additives in addition to conventional formulated excipients. These additives, such as suitable fragrances and flavorings, allow the host animal to eat on its own. Because of the simple performance of oral administration, oral administration is one of the preferred subjects of the present invention. Other dosage forms are, for example, parenteral administration by subcutaneous injection, intravenous injection or topical administration, or in the form of implants or long-term preparations (stored forms) such as injection of microcapsules (so-called "microspheres").
    [62] In addition, oral administration may include animal feed, for example dog and cat feed, such as biscuits, chewing gum, containing the active substance already mixed in water-soluble form that can be loaded onto the feed or in admixture with the animal feed. Administration as a water soluble capsule or tablet. Implants also include any device that can be inserted into an animal's body to deliver material.
    [63] Transdermal administration forms include, for example, subcutaneous administration, skin administration, intramuscular administration, and intravenous administration in injectable forms. Apart from conventional syringes with needles, needleless systems, pour-on preparations and spot-on preparations may also be used.
    [64] By selecting the appropriate formulation, it is possible to increase the ability of the active ingredient to penetrate the biological tissues of the animal and maintain its efficacy. This is important, for example, when more than one active ingredient with low solubility is used, since low solubility of the active ingredient requires a solubility-elevating method because animal fluids can only dissolve a small amount of material at a time.
    [65] In addition, the active ingredients may be present in the matrix preparation, which physically prevents their degradation and maintains the efficacy of the active ingredient. This matrix formulation is injected into the body and remains in the body in the form of algae, from which the active ingredient is continuously released. Such matrix formulations are known to those skilled in the art. These are generally waxy semisolid excipients such as plant waxes and copolymers of high molecular weight polyethylene glycols or degradable polyesters.
    [66] The good efficacy of the active ingredient can also be obtained by inserting an implant of the active ingredient into the animal. Such implants are widely used in veterinary medicine and are often composed of silicone-containing rubber. Here, the active ingredient is distributed in the solid rubber or found inside the hollow rubber element. The active ingredient that is soluble in the rubber graft must be selected because the active ingredient first dissolves in the rubber and steadily penetrates from the rubber material into the body fluid of the animal to be treated.
    [67] The rate at which the active ingredient is released from the implant and the time during which the implant is active are determined by the accuracy of the measurement of the amount of active ingredient included in the implant, the environment of the implant and the polymer formulation making the implant.
    [68] Administration of the active ingredient by an implant represents another preferred configuration of the invention. This form of administration is very economical and efficient because the correct size of the implant ensures a certain concentration of active substance in the tissue of the host animal. Currently, implants can be designed and implanted in a simple manner so that the implant is in a position to deliver the active ingredient over months.
    [69] Administration of veterinary drugs added to animal feed is best known in the field of animal health. Usually, among other things, so-called premixes are produced in which the active substance is dispersed in a liquid or finely distributed in a solid carrier. This premix may typically contain about 1 to 800 g of material per kg depending on the desired final concentration in the feed.
    [70] In addition, it is also known that the active ingredient may be hydrolyzed by the ingredients of the feed or the effect may be diminished. These active substances can typically be formulated into protective matrices such as gelatin and added to the post premix.
    [71] The compound of formula 1 according to the present invention can be used alone or in combination with other pesticides. The compounds of the present invention may be combined with pesticides having the same active range, for example, to increase the activity, or may be combined with substances having different active ranges, for example, to broaden the active range. It may also be desirable to add so-called insect repellents. For example, if the range of activity should be wide enough to affect internal parasites, eg, parasites, the compound of formula 1 is suitably combined with a substance that exhibits parasitic resistance to internal parasites. Of course, the compound of formula 1 may also be used in combination with the antimicrobial composition.
    [72] Since the compounds of formula (1) exhibit only an antiparasitic effect, ie they are specifically effective against the adult stage of the target parasite, it may be very advantageous to add an effective insecticide to the larval stage of the parasite. In this way, the majority of parasites with very large economic losses will be controlled. In addition, this approach will substantially contribute to avoiding resistant agents. In addition, many combinations can lead to a synergistic effect, i.e. a reduction in the total amount of active ingredient, which is desirable from an economic point of view. The names of the preferred groups of formulation partners and particularly preferred formulation partners are as follows, and the formulation may contain one or more of these partners together with the compound of formula (1).
    [73] Suitable partners in the mixture include insecticides known to those skilled in the art for a long time, such as various anti-insecticides and anti-mite agents, such as chitin synthesis inhibitors, growth regulators, which are known to those skilled in the art for a long time; Active ingredients that act as larval hormones; Active ingredients that act as adult insecticides; Broad-range anti-insecticides, broad-range anti-mite and anti-nematode agents; And well-known insect repellents and insect- and / or mite-repelling substances, such insect repellents or desorbers.
    [74] Non-limiting examples of suitable anti-insects and anti-mite agents are as follows:
    [75] (I) aldicarbs; (II) azineforce-methyl; (III) benpuracarb; (IV) bifenthrin; (V) buprofezin; (VI) carbofuran; (Vll) dibutylaminothio; (VIl) cartab; (IX) chlorfluazuron; (X) chlorpyrifoss; (Xl) cyfluthrin; (Xll) lambda-sihalothrin; (XIII) alpha = cifermethrin; (XIV) zeta-cifermethrin; (XV) deltamethrin; (XVI) diflubenzuron; (XVII) endosulfan; (XVIII) thiophencarb; (XIX) phenythrothione; (XX) phenobucarb; (XXI) penvalerate; (XXII) formothione; (XXIII) methiocarb; (XXIV) heptenophos; (XXV) imidacloprid; (XXVI) isoprocarb; (XXVII) metamidose; (XXVIII) metomil; (XXIX) mevinforce; (XXX) parathion; (XXXI) parathion-methyl; (XXXII) posalon; (XXXIII) pyricarb; (XXXIV) propoxur; (XXXV) teflubenzuron; (XXXVI) terbufoss; (XXXVII) triamate; (XXXVIII) abamectin; (XXXIX) phenobucarb; (XL) tebufenozide; (XLI) fipronil; (XLII) beta-cifluthrin; (XLIII) silaflofen; (XLIV) fenpyroximate; (XLV) pyridaben; (LI) avermectin B 1 ; (XLVI) penazaquin; (XLVII) pyriproxyfen; (XLVIII) pyrimidifene; (XLIX) nitenpyram; (L) NI-25, acetamiprid; (LII) insect-active extracts from plants; (Llil) preparations containing insect-active nematodes; (LIV) agents obtained from Bacillus subtilis; (LV) preparations containing insect-active fungi; (LVI) agents containing insect-active viruses; (LVII) AC 303 630; (LVIII) acepart; (LIX) acrinatrin; (LX) alaniccarb; (LXI) alphamethrin; (LXII) amitraz; (LXIII) AZ 60541; (LXIV) azineforce A; (LXV) azineforce M; (LXVI) azocyclotin; (LXVII) bendiocarb; (LXVIII) bensultab; (LXIX) betafluflurin; (LXX) BPMC; (LXXI) brofenprox; (LXXII) bromophos A; (LXXIII) bufencarb; (LXXIV) butocarboxycin; (LXXV) butylpyridaben; (LXXVI) cardusaphas; (LXXVII) carbaryl; (LXXVIII) carbophenothione; (LXXIX) clotocarb; (LXXX) chlorethoxyforce; (LXXXI) chlormefoss; (LXXXII) cis-resmethrin; (LXXXIII) clocitrin; (LXXXIV) clofentezin; (LXXXV) cyanoforce; (LXXXVI) cycloprotrin; (LXXXVII) cyhexatin; (LXXXVIII) demethone M; (LXXXIX) Demethone S; (XC) demethone-S methyl; (XCI) diclopentione; (XCII) Diclifoss; (XCIII) diethion; (XCIV) dimethatoart; (XCV) dimethylbinforce; (XCVI) dioxation; (XCVII) edifeneforce; (XCVIII) emamectin; (XCIX) esfenvalerrat; (C) ethion; (CI) etofenprox; (CIl) etoproforce; (CIII) etrimforce; (CIV) phenamifoss; (CV) fenbutatinoxide; (CVI) phenothiocarb; (CVII) phenpropatrine; (CVIII) fenpyrad; (CIX) pention; (CX) fluazinam; (CXI) flucycloxon; (CXII) flucitrinat; (CXIII) flufenoxuron; (CXIV) flufenprox; (CXV) phonoforce; (CXVI) phosphiazat; (CXVII) pufenfenrox; (CXVIII) HCH; (CXIX) hexaflumuron; (CXX) hexithiax; (CXXI) Ifprobenfoss; (CXXII) isopenfoss; (CXXIII) isoxation; (CXXIV) ivermectin; (CXXV) lambda sihalothrin; (CXXVI) malathion; (CXXVII) mecarbam; (CXXVIII) mesulfenfoss; (CXXIX) metaldehyde; (CXXX) metholcarb; (CXXXI) milbemectin; (CXXXII) moxidecin; (CXXXIII) nal red; (CXXXIV) NC 184; (CXXXV) ometoart; (CXXXVI) oxamil; (CXXXVII) oxydemethone M; (CXXXVIII) Oxidedefoss; (CXXXIX) permethrin; (CXL) pentoart; (CXLI) forrat; (CXLII) phosmet; (CXLIII) bombardment; (CXLIV) pyrimifos M; (CXLV) pyrimifos A; (CXLVI) promecarb; (CXLVII) propaphos; (CXLVIII) prothioforce; (CXLIX) protoart; (CL) pyraclophos; (CLI) pyrada-pention; (CLII) pyresmethrin; (CLIII) pyrethium; (CLIV) RH 5992; (CLV) salityone; (CLVI) Cebu Force; (CLVII) sulfotep; (CLVIII) sulfpropos; (CLIX) tebufenpyrad; (CLX) tebupyrimforce; (CLXI) tefluthrin; (CLXII) temefoss; (CLXIII) terbam; (CLXIV) tetrachlorbinforce; (CLXV) thiaphenox; (CLXVI) thiodicarb; (CLXVII) thiophanox; (CLXVIII) thionazine; (CLXIX) thuringiensin; (CLXX) tralomethrin; (CLXXI) triartene; (CLXXII) triazofoss; (CLXXIII) triazurone; (CLXXIV) trichlorphone; (CLXXV) triflumuron; (CLXXVI) trimetacarb; (CLXXVII) bamidothione; (CLXXVIII) xylylcarb; (CLXXIX) Yl 5301/5302; (CLXXX) zetamethrin; (CLXXXI) DPX-MP062; (CLXXXII) RH-2485; (CLXXXIII) D 2341; (CLXXXIV) XMC (3,5, -xylylmethylcarbamat); (CLXXXV) loufenuron; (CLXXXVI) fluazuron; (CLXXXVII) metoprene; (CLXXXVIII) hydroprene; (CLXXXIX) phenoxycarb; (CXC) chlorfenapyr; Or (CXCI) spinosad.
    [76] Non-limiting examples of suitable antiparasitic agents are described below, some of which also exhibit anti-insect and anti-mite activity in addition to parasitic activity, and some are already on the list.
    [77] (A1) prajikuantel = 2-cyclohexylcarbonyl-4-oxo-1,2,3,6,7,11 b-hexahydro-4H-pyrazino [2,1-α] isoquinoline
    [78] (A2) Chloxanthel = 3,5-diiodo-N- [5-chloro-2-methyl-4- (α-cyano-4-chlorbenzyl) phenyl] salicyamide
    [79] (A3) triclabendazole = 5-chloro-6- (2,3-dichlorphenoxy) -2-methylthio-1H-benzimidazole
    [80] (A4) levamisol = L-(-)-2,3,5,6-tetrahydro-6-phenylimidazo [2,1b] thiazole
    [81] (A5) mebendazole = (5-benzoyl-1H-benzimidazol-2-yl) carbamic acid methyl ester
    [82] (A6) ompallotin = macrocyclic fermentation product of the Omphalotus olearius fungus described in WO 97/20857
    [83] (A7) Abamectin = Avemectin B1
    [84] (A8) ivermectin = 22,23-dihydroavermectin B1
    [85] (A9) moxidecin = 5-0-demethyl-28-deoxy-25- (1,3-dimethyl-1-butenyl) -6,28-epoxy-23- (methoxyimino) -milbemycin B
    [86] (A10) Doramectin = 25-cyclohexyl-5-O-demethyl-25-de (1-methylpropyl) -avermectin A1a
    [87] (A11) Milvemectin = mixture of Milbemic Acid A3 and Milbemycin A4
    [88] (A12) Milbemycinoxime = 5-oxime of Milvemectin
    [89] Non-limiting examples of suitable insect repellents and desorbents include (R1) DEET (N, N-diethyl-m-toluamide), (R2) KBR 3023 N-butyl-2-oxycarbonyl- (2-hydroxy) -Piperidine or (R3) cymiazole = N, -2,3-dihydro-3-methyl-1,3-thiazole-2-ylidene-2,4-xylidene.
    [90] The partners in the mixtures are best known to the expert in this field. Most of them are listed in several revisions of the Pesticide Manual, The British Crop Protection Council, London, and the rest are several revisions of The Merck Index, Merck & Co., Inc., Rahway, New Jersy, USA. Or in the patent literature. Thus, the following list is limited to some cases that may be presented by way of example.
    [91] (I) 2-methyl-2- (methylthio) propionaldehyde- O -methylcarbamoyloxime (Aldicarb) (Pesticide Manual, 11 Ed. (1997), The British Crop Protection Council, London, page 26) ;
    [92] (II) S- (3,4-Dihydro-4-oxobenzo [ d ]-[1,2,3] -triazin-3-ylmethyl) O, O -dimethyl-phosphorodithioate (azine Phosph-methyl) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 67);
    [93] (III) ethyl-N- [2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl- (methyl) aminothio] -N-isopropyl-β-alanineate (benfura Carb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 96);
    [94] (IV) 2-methylbiphenyl-3-ylmethyl- ( Z )-(1 RS ) -cis-3- (2-chloro-3,3,3-trifluoroprop-1-enyl) -2, 2-dimethylcyclopropanecarboxylate (bifenthrin) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 118);
    [95] (V) 2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazin-4-one (buprofezin) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 157);
    [96] (VI) 2,3-dihydro-2,2-dimethylbenzofuran-7-yl-methylcarbamate (carbofuran) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 186);
    [97] (VII) 2,3-dihydro-2,2-dimethylbenzofuran-7-yl- (dibutylaminothio) methylcarbamate (carbosulphan) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 188);
    [98] (VIII) S, S- (2-dimethylaminotrimethylene) -bis (thiocarbamate) (cartab) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 193);
    [99] (IX) 1- [3,5-Dichloro-4- (3-chloro-5-trifluoromethyl-2-pyridyloxy) phenyl] -3- (2,6-difluorobenzoyl) -urea ( Chlorfluazuron) (The Pesticide Manual, 11 th Ed. (1997), The British Crop Protection Council, London, page 213);
    [100] (X) O, O -diethyl- O- 3,5,6-trichloro-2-pyridyl-phosphorothioate (chlorpyriphos) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 235);
    [101] (XI) ( RS ) -α-cyano-4-fluoro-3-phenoxybenzyl- (1 RS , 3 RS ; 1 RS , 3 RS ) -3- (2,2-dichlorovinyl) -2 , 2-di-methylcyclopropanecarboxylate (cifluthrin) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 293);
    [102] (XII) (S) -α-cyano-3-phenoxybenzyl- ( Z )-(1 R , 3 R ) -3- (2-chloro-3,3,3-trifluoropropenyl)- 2,2-dimethylcyclopropanecarboxylate and ( R ) -α-cyano-3-phenoxybenzyl- ( Z )-(1 R , 3 R ) -3- (2-chloro-3,3,3 A mixture of -trifluoropropenyl) -2,2-dimethylcyclopropanecarboxylate (lambda hahalthrin) (Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 300);
    [103] (XIII) ( S ) -α-cyano-3-phenoxybenzyl- (1 R , 3 R ) -3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate and ( R racemate composed of) -a-cyano-3-phenoxybenzyl- (1 S , 3 S ) -3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate (alpha- Cipermethrin) (Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 308);
    [104] (XIV) ( S ) -α-cyano-3-phenoxybenzyl (1 RS , 3 RS , 1 RS , 3 RS ) -3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecar Stereoisomeric mixtures of carboxylates (zeta-cifermethrin) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 314);
    [105] (XV) ( S ) -α-cyano-3-phenoxybenzyl- (1 R , 3 R) -3- (2,2-dibromovinyl) -2,2-dimethylcyclopropanecarboxylate ( Deltamethrin) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 344);
    [106] (XVI) (4-chlorophenyl) -3- (2,6-difluorobenzoyl) urea (diflubenzuron) (The Pesticide Manual, 11 th Ed. (1997), The British Crop Protection Council, London, page 395 );
    [107] (XVII) (1,4,5,6,7,7-hexachloro-8,9-10-trinorborn-5-ene-2,3-ylenebismethylene) -sulfite (endosulfan) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 459;
    [108] (XVIII) α-ethylthio-o-tolyl-methylcarbamate (ethiophencarb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 479);
    [109] (XIX) O, O -Dimethyl- O -4-nitro- m -tolyl-phosphothioate (phenythiion) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 514 );
    [110] (XX) 2- sec -butylphenyl-methylcarbamate (phenobucarb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 516);
    [111] (XXI) ( RS ) -α-cyano-3-phenoxybenzyl- ( RS ) -2- (4-chlorophenyl) -3-methylbutyrate (fenvallate) (The Pesticide Manual, 11th Ed. (1997) ), The British Crop Protection Council, London, page 539);
    [112] (XXII) S- [formyl (methyl) carbamoylmethyl] -O, O -dimethyl-phosphorodithioate (formomones) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council , London, page 625;
    [113] (XXIII) 4-methylthio-3,5-xylyl-methylcarbamate (methiocarb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 813);
    [114] (XXIV) 7-chlorobicyclo [3.2.0] hepta-2,6-diene-6-yl-dimethylphosphate (heptenoforce) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 670;
    [115] (XXV) 1- (6-chloro-3-pyridylmethyl) -N -nitroimidazolidin-2-ylideneamine (imidacloprid) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 706;
    [116] (XXVI) 2-isopropylphenyl-methylcarbamate (isoprocarb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 729);
    [117] (XXVII) O, S -dimethyl-phosphoramidothioate (methamidophos) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 808);
    [118] (XXVIII) S -methyl- N- (methylcarbamoyloxy) thioacetimidate (methomyl) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 815);
    [119] (XXIX) methyl-3- (dimethoxyphosphinoyloxy) but-2-enoate (melvinforce) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 844);
    [120] (XXX) O, O -diethyl- 0-4 -nitrophenyl-phosphothioate (parathion) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 926);
    [121] (XXXI) O, O -Dimethyl- O -4-nitrophenyl-phosphothioate (parathion-methyl) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 928);
    [122] (XXXII) S -6-Chloro-2,3-dihydro-2-oxo-1,3-benzoxazol-3-ylmethyl- O, O -diethyl-phosphodithioate (phosphalone) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 963);
    [123] (XXXIII) 2-dimethylamino-5,6-dimethylpyrimidin-4-yl-dimethylcarbamate (pyricarb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 985);
    [124] (XXXIV) 2-isopropoxyphenyl-methylcarbamate (propoxy) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1036);
    [125] (XXXV) 1- (3,5-dichloro-2,4-difluorophenyl) -3- (2,6-difluorobenzoyl) urea (teflubenzuron) (The Pesticide Manual, 11th Ed. 1997), The British Crop Protection Council, London, page 1158;
    [126] (XXXVI) S -tert-Butylthiomethyl- O, O -dimethyl-phosphorodithioate (terbufos) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1165) ;
    [127] (XXXVII) ethyl- (3-tert-butyl-1-dimethylcarbamoyl-1 H -1,2,4-triazol-5-yl-thio) -acetate (triamate) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1224; (XXXVIII) Abamectin, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 3);
    [128] (XXXVIII) Avermectin (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 3);
    [129] (XXXIX) 2-sec-butylphenyl-methylcarbamate (phenobucarb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 516);
    [130] (XL) N -tert-butyl- N- (4-ethylbenzoyl) -3,5-dimethylbenzohydrazide (tebufenozide) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1147);
    [131] (XLI) (±) -5-amino-1- (2,6-dichloro-α, α, α-trifluoro-p-tolyl) -4-trifluoromethyl-sulfinylpyrazole-3-carboni Tril (fipronil) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 545);
    [132] (XLII) ( RS ) -α-cyano-4-fluoro-3-phenoxybenzyl (1 RS , 3 RS ; 1 RS , 3 RS ) -3- (2,2-dichlorovinyl) -2,2 -Dimethylcyclopropanecarboxylate (beta-cifluthrin) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 295);
    [133] (XLIII) (4-ethoxyphenyl)-[3- (4-fluoro-3-phenoxyphenyl) propyl] (dimethyl) silane (silafluorene) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1105);
    [134] (XLIV) tert-Butyl ( E ) -α- (1,3-dimethyl-5-phenoxypyrazol-4-yl-methyleneamino-oxy) -p-toluate (penpyroximate) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 530;
    [135] (XLV) 2-tert-butyl-5- (4-tert-butylbenzylthio) -4-chloropyridazine-3 ( 2H ) -one (pyridaben) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1161;
    [136] (XLVI) 4-[[4- (1,1-dimethylphenyl) phenyl] ethoxy] -quinazolin (phenazquin) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 507);
    [137] (XLVII) 4-phenoxyphenyl- ( RS ) -2- (pyridyloxy) propyl-ether (pyriproxyfen) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1073 );
    [138] (XLVIII) 5-chloro- N- {2- [4- (2-ethoxyethyl) -2,3-dimethylphenoxy] ethyl} -6-ethylpyrimidin-4-amine (pyrimidipene) Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1070);
    [139] (XLIX) (E) - N - (6- chloro-3-pyridylmethyl) - N - ethyl - N - methyl-2-nitro-vinylidene-diamine (niten piram) (The Pesticide Manual, 11th Ed (1997). , The British Crop Protection Council, London, page 880;
    [140] (L) ( E ) -N 1 -[(6-chloro-3-pyridyl) methyl] -N 2 -cyano- N 1 -methylacetamidine (NI-25, acetamiprid) (The Pesticide Manual , 11th Ed. (1997), The British Crop Protection Council, London, page 9);
    [141] (LI) Avermectin B 1 (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 3);
    [142] (LII) insect-active extracts from plants, in particular (2 R , 6 aS , 12 aS ) -1,2,6,6a, 12,12a-hexhydro-2-isopropenyl-8,9-dimethoxy The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1097 -Chromeno [3,4-b] furo [2,3-h] chromen-6-one (rotenone) ); And extracts from Azadirachta indica, in particular Azadirachtin (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 59); And
    [143] (LIII) insect-active nematodes, preferably Heterorhabditis bacterophora and Heterorhabditis megidis (The British Crop Protection Council, London, page 671), Stenemema Peltier Preparations containing Steinemema feltiae (The British Crop Protection Council, London, page 1115) and Steinemema scapterisci (The British Crop Protection Council, London, page 1166);
    [144] (LIV) Bacillus subtilis (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 72), except for compounds isolated from GC91 or NCTC11821; Or agents obtainable from strains of Bacillus thuringiensis (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 73);
    [145] (LV) insect-active fungi, preferably Verticillium lecanii (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1266; Beauveria brogniartii) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 85); and Beauveria bassiana (The Pesticide Manual, 11th Ed. (1997), The Preparations containing the British Crop Protection Council, London, page 83);
    [146] (LVI) insect-active virus, preferably Neodipridon Sertifer NPV (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1342); Mamestra brassicae NPV (The Pesticide Manual, 11 th Ed. (1997), The British Crop Protection Council, London, page 759; and Cydia pomonella granulosis virus) (The Pesticide Manual, 11 th Ed. (1997), The British Crop Protection Council, London, page 291);
    [147] (CLXXXI) 7-chloro-2,3,4a, 5-tetrahydro-2- [methoxycarbonyl (4-trifluoromethoxyphenyl) -carbamoyl] indole [1,2 e ] oxazoline-4 a -carboxylate (DPX-MP062, indoxicarb) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 453);
    [148] (CLXXXII) N -tert-butyl- N ' -(3,5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (RH 2485, methoxyphenozide) (The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1094; And
    [149] (CLXXXIII) ( N ′ -[4-methoxy-biphenyl-3-yl] -hydrazinecarboxylic acid isopropyl ester (D 2341) (Brighton Crop Protection Conference, 1996, 487-493);
    [150] (R2) Abstract (212th ACS National Meeting Orlando, FL, August 25-29 (1996), AGRO-020. Publisher: American Chemical Society, Washington, D. C. CONEN: 63BFAF).
    [151] In summary, the other essential aspect of the present invention is characterized by the presence of one or more additional active ingredients having the same or different active ranges and at least one physiologically acceptable carrier, A combination formulation for controlling parasites in bleeding animals is disclosed. The present invention is not limited to a blend of the two.
    [152] The compound of formula 1 is conveniently administered to a human or host animal in an amount of 0.01 to 800, preferably 0.1 to 200, in particular 0.5 to 50 mg / kg, per kg body weight, wherein oral administration is preferred.
    [153] Preferred amounts of the compound of formula (1) which can be regularly administered to the host animal are 2.5-5 mg per kg body weight, especially in cats, and 0.5-15 mg per kg body weight, especially in dogs. Administration at regular intervals, such as every few days, weeks or months.
    [154] The total amount of the same active ingredient may vary both between and within the animal neck, since this amount depends, among other things, on the weight and composition of the animal.
    [155] For composition formulations to be administered to humans, livestock and pets, adjuvants known from veterinary practice can be used for oral, parenteral and implant forms. A list of some experimental examples is given below.
    [156] Suitable carriers are in particular fillers such as sugars (eg lactose, saccharose, mannitol or sorbitol), cellulose preparations and / or calcium phosphates such as tricalcium phosphate or calcium hydrogen phosphate, in a broader sense of the binder, For example, starch dough using corn, wheat, rice or potato starch, a binder such as gelatin, tragacanth, methyl cellulose and / or a disintegrant such as starch, if desired, and in a broader sense carboxymethyl Starch, crosslinked polyvinylpyrrolidone, agar, alginic acid or salts thereof such as sodium alginate. Excipients are in particular flow regulators and lubricants, such as silicic acid, talc, stearic acid or salts thereof such as magnesium or calcium stearate, and / or polyethylene glycols. The tablet core may optionally be suitably enteric coated, in particular concentrated sugar solutions, suitable organic solvents or solvent mixtures which may include gum gum, talc, polyvinylpyrrolidone, polyethylene glycol and / or titanium dioxide. Coating solution, or when enteric coating, can be coated using a solution of a suitable cellulose preparation such as acetylcellulose phthalate or hydroxypropylmethylcellulose phthalate. For example, dyes, fragrances or pigments may be added to the tablets or tablet coatings to confirm the use or to indicate different amounts of active ingredient.
    [157] Additional pharmaceutical compositions that are orally administrable include hard capsules composed of gelatin and soft sealed capsules composed of gelatin and a plasticizer (eg, glycerol or sorbitol). Hard capsules may contain the active ingredient in the form of granules, for example, fillers such as lactose, binders such as starch and / or lubricants such as talc or magnesium stearate, and optionally mixtures with stabilizers. have. For soft capsules, the active ingredient is preferably dissolved or suspended in a suitable liquid, such as fatty oils, paraffin oils or liquid polyethylene glycols, and stabilizers may also be added. Of these forms, capsules that are easily chewable and wholly swallowable are preferred.
    [158] Formulations suitable for parenteral administration include, in particular, aqueous solutions of the active ingredient in water-soluble form, such as aqueous solutions of water-soluble salts, in a broader sense, suspensions of the active ingredient, such as suitable lipophilic solvents or vehicles, such as oils (such as sesame oil), Or suitable injectable oily suspensions using synthetic fatty acid esters or triglycerides such as ethyl oleate, or viscosity-increasing agents such as sodium carboxymethyl cellulose, sorbitol and / or dextran, and optionally stabilizers Injectable suspensions.
    [159] The compositions of the present invention can be prepared by known methods, for example conventional mixing, granulating, coating, dissolving or lyophilizing methods. Pharmaceutical compositions for oral administration, for example, may be prepared by mixing the active ingredient with a solid carrier, optionally granulating the resulting mixture and, if desired or necessary, processing the mixture or granules to form tablets or tablet cores. Obtained by adding excipients.
    [160] The use of a compound of formula 1 according to the invention for protecting plants from parasites is at the heart of the invention.
    [161] Pests of this type arising from plants, particularly crops and decorations in agriculture, horticulture and forestry, or parts of such plants, such as fruits, flowers, leaves, stems, tubers or roots, are controlled using the active ingredients of the present invention. That is, they can be exterminated and, in some plants, these protective effects do not cause pests to occur until later.
    [162] Target crops include, in particular, cereals such as wheat, barley, rye, oats, rice, corn or sugar cane; Beets such as sugar beets or feed beets; Fruits such as poultry, nucleus and soft fruits (eg apples, pears, raisins, peaches, almonds, cherries or berries (eg strawberries, raspberries or blackberries); legumes such as beans , Lentils, peas or soybeans; oily fruits, such as grapefruit, mustard, poppy, olives, sunflowers, coconuts, beaver plants, cocoa beans or peanuts; cucumber plants, such as pumpkins, cucumbers or melons; fiber plants, such as Cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or tangerine; vegetables, such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes or paprika; laurels such as avocados , Cinnamon or camphor; and tobacco, nuts, coffee, eggplant, sugar stalks, tea, pepper, vines, hops, banana plants, natural rubber plants and decorations.
    [163] The active ingredients of the present invention are found in vegetable, fruit and rice crops, in particular, Nila parvata lugen, Heliothis virescens, Spodoptera littoralis, Diabrotica baltea It is suitable for controlling Diabrotica balteata, Panonychus ulmi, Tetranychus urticae.
    [164] Other areas of application of the active ingredients of the invention are the protection of stored goods and furnishings, the protection of raw materials, and the protection of livestock from pests of this type, particularly in the field of hygiene.
    [165] Accordingly, the present invention is directed to pesticides, including emulsifiable concentrates, suspension concentrates, sprayable or dilutable solutions, coatable ointments, dilute emulsions, comprising one or more active ingredients of the present invention, selected according to the purpose and the surrounding environment, Spray powders, soluble powders, dispersible powders, wettable powders, dust, granules or encapsulates in polymeric materials.
    [166] The active ingredient is, for example, a solid active ingredient in a pure form having a specific particle size, or preferably one or more auxiliaries, such as enhancers (solvents or solid carriers) or surface-active compounds (interfaces), which are usually used in the formulation art. Active agents) in these compositions. For parasite control in humans, livestock and pets, of course only physiologically acceptable auxiliaries are used.
    [167] For crop protection, suitable solvents include, for example, aromatic hydrocarbons (partially hydrogenated if necessary), fractions of alkylbenzenes having 8 to 12 carbon atoms (eg xylene mixtures), alkylated naphthalenes or tetrahydronaphthalenes, Aliphatic or cyclo-aliphatic hydrocarbons (such as paraffin or cyclohexane), alcohols (such as ethanol, propanol or butanol), glycols and their ethers and esters (such as propylene glycol, dipropylene glycol ethers, ethyl glycol, ethylene glycol Monomethyl or ethyl ether), ketones (eg cyclohexanone), isophorone or diacetanol alcohol, highly polar solvents (eg N-methylpyrrolid-2-one, dimethyl sulfoxide or N, N Dimethylformamide), water, optionally epoxidized vegetable oils (eg rapeseed oil, beaver oil, coconut, or epoxide if necessary) Soybean oil), and a silicone oil.
    [168] Solid phase carriers used in powders and dispersible powders are typically natural light filters such as calcite, talc, kaolin, montmorillonite or attapulgite. In order to modify the physical properties, it is also possible to add highly dispersed silicic acid or highly dispersed absorbent polymers. Suitable granulated adsorption carriers are in porous form, such as pumice, broken bricks, calculi or bentonite, and suitable non-adsorbing carriers are materials such as calsite or sand. It is also possible to use a large number of inorganic or organic pregranulated materials, such as dolomite or ground plant residues in particular.
    [169] Depending on the nature of the active ingredient used in the formulation, suitable surface active compounds are nonionic, cationic and / or anionic surfactants which are good in emulsification, dispersibility and wettability. The following surfactants are to be regarded only as examples, and the relevant literature describes many other surfactants commonly used in formulation technology and suitable for the present invention.
    [170] Preferred nonionic surfactants are aliphatic alcohols, cycloaliphatic alcohols, polyglycol ether derivatives of saturated fatty acids or unsaturated fatty acids and alkylphenols, wherein the (aliphatic) hydrocarbon residues of the derivatives contain 3 to 30 glycol ether groups and 8 There are from 20 to 20 carbon atoms and there are from 6 to 18 carbon atoms in the alkyl moiety of the alkylphenol.
    [171] Other suitable nonionic surfactants are water soluble addition products of polyethylene oxide and polypropylene glycol, ethylenediamine propylene glycol and alkylpolypropylene glycols, wherein 1 to 10 carbon atoms are present in the alkyl chain, which addition products may be from 20 to 250 Ethylene glycol ether groups and 10 to 100 propylene glycol ether groups. These compounds usually contain 1 to 5 ethylene glycol units per propylene glycol unit. Suitable nonionic surfactants are nonylphenolpolyethoxyethanol, sesame oil polyglycol ethers, polypropylene / polyethylene oxide adducts, tributylphenoxypolyethoxyethanol, polyethylene glycol and octylphenoxypolyethoxyethanol. Fatty acid esters of polyoxyethylene sorbitan such as polyoxyethylene sorbitan trioleate are also suitable.
    [172] Preferred as cationic surfactants are quaternary ammonium salts comprising at least one C 8 -C 22 alkyl radical as substituent and halogenated lower alkyl, benzyl or lower hydroxyalkyl radical as other substituents. The salt is preferably in the form of a halide, methylsulfate or ethylsulfate. Examples are stearyltrimethylammonium chloride and benzyl-di (2-chloroethyl) ethylammonium bromide.
    [173] Suitable anionic surfactants can be both water soluble soaps and water soluble synthetic surfactant compounds. Suitable soaps are alkaline metal salts, alkaline earth metal salts, unsaturated ammonium salts or saturated ammonium salts of high fatty acids (C 10 -C 22 ), for example sodium or potassium salts of oleic acid or stearic acid, or for example coconut oil or It is a sodium or potassium salt of the natural fatty acid mixture obtained from resin oil, and fatty acid methyltaurine can be used. However, synthetic surfactants are used more often, in particular fatty sulfonates, fatty sulfates, sulfonated benzimidazole derivatives or alkylarylsulfonates. Fatty sulfonates or sulfates are usually in the form of alkaline metal salts, alkaline earth metal salts, unsubstituted ammonium salts or substituted ammonium salts and comprise alkyl radicals having 8 to 22 carbon atoms and are alkyl residues of the acyl radicals, eg, lig Sodium and calcium salts of nonsulfonic acid or dodecyl sulfate, or sodium and calcium salts of fatty alcohol sulfate mixtures obtained from natural fatty acids. These compounds also include the sulfuric acid esters of fatty alcohol / ethylene oxide addition products and salts of sulfonic acids. The sulfonated benzimidazole derivatives preferably contain two sulfonic acid groups and one fatty acid radical containing 8 to 22 carbon atoms. Examples of alkylarylsulfonates are the sodium, calcium or triethanolamine salts of dodecylbenzenesulfonic acid, dibutylnaphthalenesulfonic acid, or naphthalenesulfonic acid / formaldehyde condensates. Also suitable are salts of the corresponding phosphates, such as the phosphoric acid esters of p-nonylphenol and addition products of 4 to 14 moles of ethylene oxide or phospholipids.
    [174] The term active ingredient is enantiomer A, preferably enantiomer A described in the material table below.
    [175] Compositions for crop protection and for use in humans, livestock and pets usually contain from 0.1 to 99%, in particular from 0.1 to 95% of the active ingredient and from 1 to 99.9%, in particular from 5 to 99.9% of solid or liquid auxiliaries. And usually 0 to 25%, in particular 0.1 to 20% of the composition of the composition (% in each case means wt%). Although concentrated compositions tend to be preferred as commodities, end consumers usually use diluted compositions with substantially lower concentrations of the active ingredient.
    [176] Preferred compositions of crop protection agents are in particular as follows (% = weight%).
    [177] Emulsifiable concentrate
    [178] Active ingredient: 1 to 90%, preferably 5 to 20%
    [179] Surfactant: 1 to 30%, preferably 10 to 20%
    [180] Solvent: 5 to 98%, preferably 70 to 85%
    [181] Powder
    [182] Active ingredient: 0.1 to 10%, preferably 0.1 to 1%
    [183] Solid carrier: 99.9 to 90%, preferably 99.9 to 99%
    [184] Suspension concentrate
    [185] Active ingredient: 5 to 75%, preferably 10 to 50%
    [186] Water: 94-24%, preferably 88-30%
    [187] Surfactant: 1 to 40%, preferably 2 to 30%
    [188] Wettable Powder
    [189] Active ingredient: 0.5 to 90%, preferably 1 to 80%
    [190] Surfactant: 0.5 to 20%, preferably 1 to 15%
    [191] Solid carrier: 5 to 99%, preferably 15 to 98%
    [192] Granules:
    [193] Active ingredient: 0.5 to 30%, preferably 3 to 15%
    [194] Solid phase carrier: 99.5 to 70%, preferably 97 to 85%
    [195] The activity of the crop protection agents of the invention can be substantially broadened and adapted to the prevailing environment by adding other pesticides. Additional active ingredients are, for example, organophosphorus compounds, nitrophenols and derivatives thereof, formamidine, acylurea, carbamate, pyredoids, natroenamine and derivatives thereof, pyrrole, thiourea and derivatives thereof, chlorinated Substance from hydrocarbon and Bacillus thuringiensis formulations. The compositions of the present invention may be formulated with other solid or liquid auxiliaries, such as stabilizers (e.g. vegetable oils that are optionally epoxidized, such as epoxidized coconut oil, rapeseed oil or soybean oil), defoamers (e.g. Silicone oils), preservatives, viscosity modifiers, binders and / or adhesives, as well as fertilizers or other active ingredients that exhibit a particular effect, such as anti-mite, antimicrobial, antifungal, anti-neutral, apricot, specific herbicides It may further include.
    [196] The crop protection agents of the present invention are prepared by grinding, sieving and / or compacting, for example, particles of a particular size, in the absence of an adjuvant, and in the presence of at least one adjuvant, in the presence of at least one adjuvant. Prepared in a known manner by admixing and / or grinding with the adjuvant (s), for example. The above methods of preparing the compositions of the present invention and the use of the compounds of formula 1 for preparing these compositions are also an object of the present invention.
    [197] Methods of administering crop protection agents, ie methods of controlling pests of this type, for example spraying, spraying, coating, dressing, spraying or swelling (selected according to the desired purpose and surrounding environment), controlling such types of pests The use of the composition for: is another object of the invention. Typical concentrations of the active ingredient are 0.1 to 100 ppm, preferably 0.1 to 500 ppm. Dosing rates are generally from 1 to 2000 g of active ingredient per hectare, in particular from 10 to 1000 g / ha, preferably from 20 to 600 g / ha.
    [198] A preferred method of administration for crop protection is to administer the active ingredient to the leaves of the plant (leaves administration), the frequency of administration and the rate of administration depend on the degree of infection by the pest. However, the active ingredient can penetrate through the soil to the root of the plant (systemic administration) by injecting a liquid composition into the plant or by applying a compound in solid form, for example, a granular form to the soil (soil administration). . For rice farming, granules can be administered into flooded paddy fields.
    [199] Crop protection agents of the invention are also suitable for protecting asexual propagation material, for example seeds (fruit, tubers or grains) or plant seedlings from pests. The propagation material may be treated with the composition prior to the start of tillage, for example dressing before seeding. The active ingredient of the present invention can be administered to the seed (coating) by dipping the seed in a liquid composition or by coating with a solid composition. The composition can also be applied when the propagation material is sown at the place of cultivation, for example when sowing seeds into the seed ridges. Methods of treating plant propagation material and propagation material treated thereby are also an object of the present invention.
    [200] In the following formulations for use in humans, livestock and pets, the term "active ingredient" means at least one enantiomeric active ingredient of formula (1) or a salt thereof, preferably 2- (2,6-difluorophenyl)- A-form of 4- (4'-trifluoromethylbiphenyl-4-yl) -4,5-dihydro-oxazole.
    [201] Tablets : Tablets containing one of the active ingredients of formula 1 can be prepared as follows.
    [202] Composition (for 100 tablets)
    [203] Active ingredient of formula 1: 25 g
    [204] Lactose: 100.7 g
    [205] Wheat starch: 6.25 g
    [206] Polyethylene glycol 6000: 5.0 g
    [207] Talc: 5.0 g
    [208] Magnesium Stearate: 1.8 g
    [209] Demineralized Water: Fill
    [210] Formulation: All solid components are first passed through a sieve with a mesh size of 0.6 mm. Next, half the active ingredient, lactose, talc and starch are mixed. The remaining starch is suspended in 40 ml of water and this suspension is added to the hanging polyethylene glycol solution in 100 ml water. The resulting starch dough is added to the mixture, which is then granulated, optionally with water.
    [211] The granules are dried at 35 o overnight, passed through a sieve with a mesh size of 1.2 mm, mixed with magnesium stearate and then compressed into tablets 6 mm in diameter and concave on both sides.
    [212] Tablets : Tablets each containing a total of 0.0183 g of active ingredient were prepared as follows.
    [213] Composition (if 10,000 definitions)
    [214] Active ingredient of formula 1: 183.00 g
    [215] Lactose: 290.80 g
    [216] Potato starch: 274.70 g
    [217] Stearic acid: 10.00 g
    [218] Talc: 217.00 g
    [219] Magnesium Stearate: 2.50 g
    [220] Colloidal Silica: 32.00 g
    [221] Ethanol: Enough
    [222] A mixture of 274.70 g of active ingredient, lactose and potato starch was humidified with an ethanol-based solution of stearic acid and granulated through a sieve. After drying, the remaining potato starch, talc, magnesium stearate and colloidal silica were added and the mixture was compressed to form tablets with a weight of 0.1 g each, which, if desired, can be more accurately calculated and adjusted.
    [223] Capsules : Tablets each containing a total of 0.022 g of active ingredient can be prepared as follows.
    [224] Composition (for 1000 capsules)
    [225] Active ingredient of Formula 1: 22.00 g
    [226] Lactose: 249.80 g
    [227] Gelatin: 2.00 g
    [228] Corn Starch: 10.00 g
    [229] Talc: 15.00 g
    [230] Water: fill
    [231] The active ingredient is mixed with lactose and the mixture is evenly wetted with an aqueous solution of gelatin and granulated through a sieve having a mesh size of 1.2-1.5 mm. The granules are mixed with dried corn starch and talc and 300 mg of the mixture is filled into hard gelatin capsules (Size 1).
    [232] Premix (Feed Additives)
    [233] 0.16 parts by weight of the active ingredient of formula 1 and 4.84 parts by weight of secondary calcium phosphate, alumina, aerosil, carbonate or calcium carbonate are mixed with 95 parts by weight of animal feed until homogeneous, or 0.41 parts by weight of active ingredient of formula 1 And 5.00 parts by weight of aerosil / lime are mixed with 94.59 parts by weight of commercial dry feed until homogeneous.
    [234] Call back
    [235] I. Active Ingredient 33.00%
    [236] Methylcellulose 0.80%
    [237] Highly dispersed silicic acid 0.80%
    [238] Corn starch 8.40%
    [239] II. Crystallized Lactose 22.50%
    [240] Corn Starch 17.00%
    [241] Microcrystalline Cellulose 16.50%
    [242] Magnesium Stearate 1.00%
    [243] First, methylcellulose is added to water and stirred. After the mixture is expanded, silicic acid is added and stirred, then the mixture is suspended homogeneously. The active ingredient and corn starch are mixed. The aqueous suspension is added to this mixture and kneaded into a soft mass. The resulting mass is granulated through 12 M sieve and dried. In an additional step, mix all four supplements thoroughly. Finally, the premix produced from the first two partial steps was mixed and compressed to form a ring.
    [244] Injection
    [245] A. Planetary vehicle (sustained release)
    [246] 0.1-1.0 g of active ingredient of formula 1
    [247] 100 ml of peanut oil
    [248] or,
    [249] 0.1-1.0 g of active ingredient of formula 1
    [250] 100 ml of sesame oil
    [251] Formulation: The active ingredient was dissolved in some peanut oil or sesame oil with stirring and optionally heating slowly, then cooled and filled to the desired volume and sterile filtered through a suitable membrane filter with a pore size of 0.22 μm.
    [252] Formulation example
    [253] Preparation Example P1 : Enantiomer A of 2- (2,6-difluoro-phenyl) -4- (4'-trifluoromethylbiphenyl-4-yl) -4,5-dihydro-oxazole and Manufacture of B
    [254] a) The enantiomeric mixture is dissolved in a solvent mixture comprising 40 ml of ethanol and 60 ml of hexane and firstly a Chiralcel column with a hexane / isopropanol mixture (9: 1) at a flow rate of 150 ml / min. (OD 10 × 50 cm)) for 120 minutes and then chromatographed on the column with pure ethanol at a flow rate of 100 ml / min for 80 minutes. After 31 minutes, the maximum peak of enantiomer A of the title compound was reached and after 49 minutes the maximum peak of enantiomer B was reached.
    [255] b) The enantiomeric mixture was dissolved in pure ethanol and chromatographed on a Chiralcel column (OJ (1082) 25 × 0.46 cm) with pure ethanol at a flow rate of 1 ml / min. After 5.5 minutes, the maximum peak of enantiomer A of the title compound was reached and after 7.5 minutes the maximum peak of enantiomer B was reached.
    [256] Preparation P2 : The other compounds of Table 1 can also be prepared in a manner similar to that of Preparation P1.
    [257] TABLE 1
    [258]
    [259] Number XY (R 1 ) m enantiomer optical rotation 11.1 FF 4-CF 3 A -24. 3 (20.7mg) 1.2 FF 4-CF 3 B +23.8 (21 mg) 1.3 FF 4-CH 3 A 1.4 FF 4-CH 3 B 1.5 FF 4-OCF 3 A 1.6 FF 4-OCF 3 B 1.7 FF 3-CF 3 A 1.8 FF 3-CF 3 B 1.9 FF 4-OCF 2 CHF 2 A 1.10 FF 4-OCF 2 CHF 2 B 1.11 FF 4-OCHF 2 A 1.12 FF 4-OCHF 2 B 1.13 FF 4-SCF 3 A 1.14 FF 4-SCF 3 B 1.15 FF 4-CF 2 CN A 1.16 FF 4-CF 2 CN B 1.17 FF 3-CH 3 , 4-CF 3 A 1.18 FF 3-CH 3 , 4-CF 3 B 1.19 F Cl 4-OCF 3 A 1.20 F Cl 4-OCF 3 B
    [260] α D (589 nm Na D ) (soluble in 2 ml methanol)
    [261] Examples of preparations used for crop protection (% = weight%)
    [262] Formulation Example F1: Emulsion Concentrate a) b) c)
    [263] Active ingredient of Formula 1 25% 40% 50%
    [264] Calcium Dodecylbenzenesulfonate 5% 8% 6%
    [265] Beaver Oil Polyethylene Glycol Ether (36 mol EO) 5%--
    [266] Tributyl phenol polyethylene glycol ether (30 mol EO)-12% 4%
    [267] Cyclohexanone-15% 20%
    [268] Xylene Mixture 65% 25% 20%
    [269] The finely ground active ingredient and the adjuvant were mixed to obtain an emulsion concentrate, which was diluted with water to give an emulsion of the desired concentration.
    [270] Preparation Example F2: Solution a) b) c) d)
    [271] Active ingredient of formula 1 80% 10% 5% 95%
    [272] Ethylene Glycol Monomethyl Ether 20%---
    [273] Polyethylene Glycol (MW 400)-70%--
    [274] N-methylpyrrolid-2-one-20%--
    [275] Epoxidized Coconut Oil--1% 5%
    [276] Gasoline (boiling point: 160-190 O )--94%-
    [277] The finely ground active ingredient and the adjuvant were mixed to obtain a solution suitable for administration in the form of fine drops.
    [278] Formulation Example F3: Granules a) b) c) d)
    [279] Active ingredient of formula 1 5% 10% 8% 21%
    [280] Kaolin 94%-79% 54%
    [281] Highly dispersed silicic acid 1%-13% 7%
    [282] Atapulgite-90%-18%
    [283] The active ingredient is dissolved in dichloromethane, the solution is sprayed onto the carrier mixture and the solvent is removed by evaporation in vacuo.
    [284] Formulation Example F4: Powder a) b)
    [285] Active ingredient of formula 1 2% 5%
    [286] Highly dispersed silicic acid 1% 5%
    [287] Talc 97%-
    [288] Kaolin-90%
    [289] The powder is prepared for immediate use by mixing the active ingredient with the carrier.
    [290] Formulation Example F5: Wettable Powder a) b) c)
    [291] Active ingredient of formula 1 25% 50% 75%
    [292] Sodium Ligninsulfonate 5% 5%-
    [293] Sodium Lauryl Sulfate 3%-5%
    [294] Sodium Diisobutyl Naphthalene Sulfonate-6% 10%
    [295] Octylphenol Polyethylene Glycol Ether (7-8 Mole EO)-2%-
    [296] Highly dispersed silicic acid 5% 10% 10%
    [297] Kaolin-62% 27%
    [298] The active ingredient and the adjuvant were mixed and the mixture was ground in a suitable mill.
    [299] Dilution with water gave a wettable powder that could be a suspension of the desired concentration.
    [300] Formulation Example F6: Emulsion Concentrate
    [301] 10% active ingredient of formula 1
    [302] Octylphenol Polyethylene Glycol Ether (4-5 Mole EO) 3%
    [303] Calcium Dodecylbenzenesulfonate 3%
    [304] Beaver oil polyethylene glycol ether (36 mol EO) 4%
    [305] Cyclohexane 30%
    [306] Xylene Mixture 50%
    [307] The finely ground active ingredient and adjuvant are mixed to obtain an emulsion concentrate, which is diluted with water to give an emulsion of the desired concentration.
    [308] Formulation Example F7: Powder a) b)
    [309] Active ingredient of Formula 1 5% 8%
    [310] Talc 95%-
    [311] Kaolin-92%
    [312] Ready-to-use powders are obtained by mixing the active ingredient with the carrier and then grinding the mixture in a suitable mill.
    [313] Formulation Example F8 Extruded Granules
    [314] 10% active ingredient of formula 1
    [315] Sodium Lignin Sulfonate 2%
    [316] Carboxymethylcellulose 1%
    [317] Kaolin 87%
    [318] The active ingredient and the adjuvant were mixed, the mixture was ground, humidified with water, extruded and granulated, and the granules were dried in an air stream.
    [319] Formulation Example F9: Coated Granules
    [320] 3% active ingredient of formula 1
    [321] Polyethylene Glycol (MW 200) 3%
    [322] Kaolin 94%
    [323] The finely ground active ingredient was added homogeneously to the kaolin humidified with polyethylene glycol in a mixer to obtain dust-free coated granules.
    [324] Formulation Example F10: Suspension Concentrate
    [325] 40% active ingredient of formula 1
    [326] Ethylene Glycol 10%
    [327] Nonylphenol Polyethylene Glycol Ether (15 mol EO) 6%
    [328] Sodium Lignin Sulfonate 10%
    [329] Carboxymethylcellulose 1%
    [330] Formaldehyde aqueous solution (37%) 0.2%
    [331] Aqueous Silicone Oil Emulsion (75%) 0.8%
    [332] 32% of water
    [333] The finely ground active ingredient and the adjuvant were mixed to obtain a suspension concentrate, which was diluted with water to give a suspension of the desired concentration.
    [334] Biological Experiment
    [335] Example used for crop protection
    [336] Experimental Example B1 : Salan Effect on Heliothis virescens
    [337] For testing in acetone / water, the eggs of heliotis viresense suspended on filter paper were briefly immersed in a test solution containing 400 ppm of active ingredient. After drying the test solution, the eggs were incubated in a petri dish. After 6 days, the hatching rate (%) of the eggs was compared to the hatching rate of the untreated control (% reduction in hatching rate).
    [338] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of at least 80%.
    [339] Experimental Example B2 : Effects on Diabrotica balteata Larva
    [340] An aqueous solution of an emulsion spray mixture containing 400 ppm of active ingredient was sprayed onto the corn seedlings. After the spray deposits were dried, the corn seedlings were infected with 10 second-phase larvae of Diabrotica valteata and placed in plastic containers. After 6 days, the seedlings were observed. The percentage reduction in larval numbers (% reactivity) was calculated by comparing the number of dead larvae on treated corn to the number of dead larvae on untreated corn.
    [341] Enantiomer A of Table 1 showed excellent efficacy against Diabrotica Valteata in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [342] Experimental Example B3 : Effect on Tetranychus urticae
    [343] The young bean plants were infected with the mixed tetranicus urtica community and after 1 day, the plants were sprayed with an aqueous emulsion spray mixed solution containing 400 ppm of active ingredient. The plants were then incubated at 25 ° C. for 6 days and then observed. The percentage reduction (% reactivity) of the tetranicus urtica number was calculated by comparing the total number of dead eggs, larvae, and adults on the treated plants with the dead number on untreated corn.
    [344] Enantiomer A of Table 1 showed excellent efficacy against tetranicus urtica in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [345] Experimental Example B4 : Effect on Heliotis nonresense caterpillar
    [346] An aqueous solution of an emulsion spray mixture containing 400 ppm of active ingredient was sprayed onto young soybean plants. After the spray deposits were dried, the soybean plants were infected with 10 heliotis nonresense larvae of the first-phase and placed in plastic containers. After 6 days, the plants were observed. The reduction rate of larvae number and the reduction rate of nutrient damage (% reactivity) were calculated by comparing the number of dead larvae on the treated plants and the degree of nutrient damage to the number of untreated plants and the degree of damage.
    [347] Enantiomer A of Table 1 showed excellent efficacy against heliotis nonresense in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [348] Experimental Example B5 : Effect on Caterpillar Plutella xylostella
    [349] A young aqueous cabbage plant was sprayed with an emulsion spray mixed aqueous solution containing 400 ppm of active ingredient. After the spray coating was dried, the cabbage plants were infected with 10 third-term caterpillars of flutella xylostella and placed in plastic containers. After 3 days, the plants were observed. The reduction rate of larvae number and the reduction rate of nutrient damage (% reactivity) were calculated by comparing the number of dead larvae on the treated plants and the degree of nutrient damage to the number of untreated plants and the degree of damage.
    [350] Enantiomer A of Table 1 showed excellent efficacy against flutella xyclestella in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [351] Experimental Example B6 : Salan / larvae effect on heliotis non-resense
    [352] Aqueous emulsion spray mixed aqueous solution containing 400 ppm of active ingredient was sprayed onto the eggs of turmeric heliotis nonresense on cotton. After 8 days, the hatching rate of the eggs and the survival rate of the caterpillars were compared with the hatching rate and survival rate of the untreated control (% of population reduction).
    [353] Enantiomer A of Table 1 showed excellent efficacy against heliotis nonresense. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [354] Experimental Example B7: scattering effect on tetranicus urtica
    [355] The young bean plants were infected with female tetranicus urtica and the tetranicus urtica was removed after 24 hours. An aqueous solution of an emulsion spray mixture containing 400 ppm of active ingredient was sprayed onto the infected plants with eggs. The plants were observed after incubation at 25 ° C. for 6 days. The percentage reduction in population (% reactivity) was calculated by comparing the total number of dead eggs, larvae, and adults on the treated plants with the number of untreated plants.
    [356] Enantiomer A of Table 1 showed excellent efficacy against tetranicus urtica in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [357] Experimental Example B8 : Effect on Panonicus ulmi (indicating resistance to organophosphate and cabaryl)
    [358] Apple seedlings were infected with female Panonicus wool adults. After 7 days, the aqueous spray spray mixture containing 400 ppm of the active ingredient was sprayed onto the infected plants and grown in a greenhouse until the infected plants were soaked. After 14 days, the plants were observed. The percentage reduction (% reactivity) of the number of ticks was calculated by comparing the number of dead spider mites on the treated plants with the number of untreated plants.
    [359] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [360] Experimental Example B9: Effect on Nilaparvata lugens
    [361] An emulsion spray mixed aqueous solution containing 400 ppm of active ingredient was sprayed onto rice. After the spray coating was dried, the rice was infected with the second and third young larvae of the plant leaf beetle. After 21 days, the plants were observed. The reduction rate (% reactivity) of the leafworm number was calculated by comparing the number of leafworms on the treated plants with the number of untreated plants.
    [362] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [363] Experimental Example B10 : Effect on Spodoptera littoralis
    [364] An aqueous solution of an emulsion spray mixture containing 400 ppm of active ingredient was sprayed onto young soybean plants. After the spray deposits were dried, the plants were infected with 10 third-level larvae of Spodoptera litoralis and placed in plastic containers. After 3 days, the plants were observed. The reduction rate and nutrient damage rate (% reactivity) of the larvae was calculated by comparing the total number and nutrient damage of dead caterpillars on the treated plants with the total number and degree of damage on the untreated plants.
    [365] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [366] Experimental Example B11 : Effect on Amphis craccivora
    [367] After pea seedlings were infected with Ampis Krasibora, a spray mixture containing 400 ppm of active ingredient was sprayed onto the seedlings and then incubated at 20 ° C. After 3 and 6 days, the seedlings were observed. The percent reduction in aphid number was calculated by comparing the number of dead aphids on the treated seedlings with the number of untreated seedlings on the seedlings.
    [368] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [369] Experimental Example B12 : Effect on Crosidolomia binotalis
    [370] A spray mixed aqueous solution containing 400 ppm of active ingredient was sprayed onto young cabbage plants. After the spray coating was dried, the cabbage plants were infected with 10 third-term caterpillars of Crosidolomia vinotalis and placed in plastic containers. After 3 days, the plants were observed. The reduction rate and nutrient damage rate (% reactivity) of the number of larvae were calculated by comparing the total number of larvae and the nutrient damage to the treated plants with the number and nutrient damage to the untreated plants.
    [371] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [372] Experimental Example B13 : Effect on Anthonomus arandis
    [373] Aqueous emulsion spray mixed aqueous solution containing 400 ppm of active ingredient was sprayed into young cotton water. After the spray coating was dried, the cotton water was infected with 10 Ansonomus arandis adults and placed in plastic. After 3 days, the plants were observed. The reduction rate and nutrient damage rate (% reactivity) of the beetle number was calculated by comparing the total number of larvae killed and the nutritional damages on the treated plants with the total number and nutrient damages of the untreated plants.
    [374] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [375] Experimental Example B14 : Effect on Aonidiella aurantii
    [376] Potato tubers were infected with larvae of Aonidiaella orantii. After two weeks, the potatoes were immersed in an emulsion or suspension spray mixed aqueous solution containing 400 ppm of active ingredient. The tubers were dried and then incubated in a plastic container. After 10-12 weeks, the survival of the first generation 2 larvae of the treated group was compared with that of the untreated control.
    [377] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [378] Experimental Example B15 : Effect on Bemisia tabaci
    [379] Young soybean plants were placed in gauze cages and infected with adult Bemiscia tabaki. After spawning, all adults were removed. After 10 days, an emulsion spray mixed aqueous solution containing 400 ppm of active ingredient was sprayed onto the plant and the larvae on the plant. After 14 days, the hatching rate of eggs was compared with that of untreated control.
    [380] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reaction of 80% or more.
    [381] Examples of use in medicine and hygiene
    [382] Experimental Example B16 : In vitro effect on Boophilus microplus
    [383] For four series of tests, each congested female Buffulus microplus was fixed on a plastic plate and covered with a bundle of cotton wool soaked with an aqueous solution of emulsion or emulsion for 1 hour. This test was performed at concentrations of 100, 32, 10, 3.2, 1.0 and 0.32 ppm. The bundle of cotton wool was then removed and the ticks incubated for 28 days to spawn. The effect on Bupillius microplus was calculated according to the following five criteria.
    [384] 1. the number of females (uncolored and not moving) that died before spawning;
    [385] 2. Number of ticks that did not spawn but survived for several days;
    [386] 3. the number of cases that spawned but did not hatch;
    [387] 4. The number of cases when spawned and embryos hatched from eggs but this embryo did not develop into larvae;
    [388] 5. The number of cases in which the embryo hatched and developed as a larva but showed no metamorphosis within 4 weeks.
    [389] In this test enantiomer A of formula 1 showed the effect described in step 4. These substances inhibited larval hatching 100% at concentrations of 100, 32, 10 and 3.2 ppm. Even at 1 ppm the hatching rate was suppressed 60-90%. Thus, Enantiomer A of 2- (2,6-difluorophenyl) -4- (4'-trifluoromethylbiphenyl-4-yl) -4,5-dihydro-oxazole has the highest activity It is a high test substance. In contrast, enantiomer B of Formula 1 showed substantially no activity under the same conditions.
    [390] This test was performed on both BIARRA and ULAM strains and the results in both cases were the same.
    [391] Experimental Example B17 2- (2,6-difluorophenyl) -4- (4'-trifluoromethylbiphenyl-4-yl) -4,5- against Dermanyssus gallinae In Vitro Comparison of Enantiomers A and B of Dihydro-Oxazole with Enantiomers
    [392]
    [393] Fifteen female ticks in the genus Dermanisus galli fixed on a plastic adhesive film were contacted with 50 μl of suspension or aqueous solution of test substance. This test was performed at concentrations of 32, 10, 3.2, 0.32 to 0.1 ppm. The film was dried and then fixed on a glass plate. This resulted in bubbles around each tick, the bottom of which was formed by the glass plate and the top by the expansion of the adhesive film. This bubble contained enough air to prevent ticks from choking. After 5 days, the effect of the test substance was measured by using a stereomicroscope to determine mortality, turbidity, egg quality, hatching rate, pupation rate, and effects on the development of larvae according to the following four criteria: Was evaluated.
    [394] 1. If 9 to 10 ticks die, this has a fatal effect (M);
    [395] 2. If two or more ticks survived but did not spawn at all, this means infertility (S);
    [396] 3. If two or more mites survive and spawn but do not hatch at all from the larvae and do not develop into larvae, this means a development-inhibitory effect (H);
    [397] 4. If two or more ticks survive and produce a normal number of normal eggs, from which the larvae hatch and develop into larvae, this means no activity.
    [398] The racemate mixture showed the effect described in step 1 in this test. The mixture completely inhibited development into larvae at concentrations of 0.02 ppm or more. Enantiomer A already exhibited the same effect at very low concentrations of 0.0064 ppm and at much lower concentrations. Enantiomer B showed no effect at concentrations below 10 ppm (see no. 4) and was indistinguishable from untreated controls. To obtain significant efficacy, the concentration of Enantiomer B had to be at least 20 ppm, and even at this concentration, only type 3 activity could be exhibited. The concentration of enantiomer B to show activity of type 1 should be at least 32 ppm. The results are summarized as follows (EC 100 = minimum amount to reach 100% mortality).
    [399] Test Compound EC 100 (ppm) Activity Type
    [400] Racemate 0.2 1
    [401] Enantiomer A 0.0064 1
    [402] (Enantiomer B 20.0 3)
    [403] Enantiomer B 32.0 1
    [404] This shows that the activity of Enantiomer A is at least 30 times higher than that of the racemate and even 3000-5000 times higher than the activity of Enantiomer B.
    [405] Experimental Example B18 : In Vitro Effects on Australian Sheep Blackfly Lucilia cuprina
    [406] In a test tube, 4 ml of culture medium suitable for the black fly larvae on the agar substrate were heated to liquefy and mixed with 10 ml of suspension or emulsion test solution. The mixture was cooled to give a solidified culture medium. Test tubes containing test materials at concentrations of 10, 3.2, 1 and 0.32 ppm were prepared. The solidified culture medium was inoculated with 30-50 eggs of freshly laid Lucilia cupri or black fly, the test tubes were loosely sealed with cotton wool and incubated at 26-28 ° C. After 4 days, the test tube was removed from the incubator to determine the anti-larval effect of the test substance. If the larvae surviving in the third developmental stage are found in the liquefied brown culture medium, this indicates no anti-larval effect. On the contrary, if the culture medium remains undiscolored and solidified and no larvae are found, this means 100% anti-larval activity. In this test, Enantiomer A of Formula 1 showed 100% anti-larval effect on black flies at all test concentrations. In contrast, enantiomer B of Formula 1 did not show substantially activity under the same conditions.
    [407] Experimental Example B19 : Effect on Blattella germanica
    [408] The solution was added to the petri dish so that the amount of acetone solution containing the active ingredient corresponds to the addition rate of 2 g / m 2 . When the solvent evaporated, 20 larvae of the blastella germanica (last larval stage) were placed in a dish and exposed to the action of the test substance for 2 hours. Next, the larvae were anesthetized with CO 2, then transferred to a new petri dish, placed in a dark room under the condition of 25 O and 50 to 70% humidity. After 48 hours, mortality was measured to assess the anti-insect effect.
    [409] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reactivity of at least 80%.
    [410] Experimental Example B20 : Effect on Musca domestica
    [411] The sugar cubes were treated with the test substance solution in such a way that the concentration of the test substance in the sugar after drying overnight was 250 ppm. The cubes treated in this way were placed on an aluminum dish containing cotton and 10 adults of Musca domestica, an OP-resistant strain. This dish was covered with a beaker and incubated at 25 ° C. Mortality was measured after 24 hours.
    [412] Enantiomer A of Table 1 showed excellent efficacy in this test. In particular, Enantiomer A of Preparation Example P1 showed a reactivity of at least 80%.
    [413] Experimental Example B21 : In Vitro Effect on Egg, Larva or Pupa of Cat Flea, Stenocephalides felis
    [414] Acetone test solutions were prepared containing test materials at 15, 1.5, 0.15 and 0.015 ppm concentrations. 9.9 ml of each test solution was mixed with 14.58 g of culture medium for flea larvae and dried for about 12 hours. The medium was mechanically ground again until the slightly lumped dry culture medium was homogeneous and freely flowing. Next, the mixture was transferred to a flea breeding bottle, 100 to 200 flea eggs were added, the bottle was loosely sealed with a cotton ball, and then incubator with a temperature of 25 to 26 ° C. and a relative humidity of about 60%. Put on. After 21 days, the effect of the test substance was measured at various concentrations and the lowest effective concentration was determined using a stereomicroscope. Activity was measured based on hatching rate, larval development, pupa development and hatching of fleas. Enantiomer A of Formula 1 showed noticeable effects in this test. At concentrations below 10 ppm, flea outbreaks have been shown to be completely inhibited. Thus, Enantiomer A of 2- (2,6-difluorophenyl) -4- (4'-trifluoromethylbiphenyl-4-yl) -4,5-dihydro-oxazole has the highest activity It is a high test substance. In contrast, enantiomer B of Formula 1 did not show substantially activity under the same conditions.
    [415] Experimental Example B22 : In Vitro Effects of Haemonchus contortus on the Third Stage Larvae
    [416] 2 μl of a 5% test substance solution in DSMO or methanol was diluted with additional solvent and the inside of the test tube was wetted with the solution. After drying, 2 ml of agar was added to each test tube. Each test tube was infected with 100 Hamoncus Contortus fresh eggs in deionized water, and the test tubes were loosely sealed with a cotton wool and placed in an incubator with a temperature of 34 to 36 ° C. and a relative humidity of about 60 to 100%. Twenty four hours after incubation of the larvae, 30 μl of bacterial culture medium was added to allow replication of the freshly introduced bacteria. The volume of water should be about one third filling the test tube. The effect of the test substance was measured based on hatching rate, development of stage 3 larvae, paralysis or death of larvae, or other stages of development. Enantiomer A of Formula 1 showed significant developmental inhibition in this test. At concentrations below 32 ppm it has been shown that the development of stage 3 larvae is completely suppressed. In contrast, enantiomer B of Formula 1 did not show substantially activity under the same conditions.
    [417] Experimental Example B23 : In vivo effect of topical treatment against infection with mouse hair mites
    [418] Mice infected with ticks (Myocopetes musculinus and Mubia muscull) were anesthetized and the density of the tick community was examined under stereomicroscopy. The mice were divided into groups with the same infection index, ranging from grades 1 (no ticks) to grades 30 (highest tick density), ie, in each case with the same tick population. For testing purposes, only mice with an index of at least 25 grade (high tick density) were used. Test substances were administered in the form of pourable solutions, suspensions or emulsions, ie topically to the hair. Dosage was 32 to 0.1 mg / kg body weight. 150 μl of solution, suspension or emulsion per mouse was administered along the top line. Efficacy was measured by comparing the infection index after administration with the infection index after 7 days, 28 days and 56 days after administration. Efficacy is expressed as a decrease in tick population.
    [419] In this test, Enantiomer A of Formula 1 had a reduction of mite infection rate of 80% or more at a concentration of 10 mg / kg (body weight) or less. In contrast, enantiomer B of Formula 1 did not show substantially activity under the same conditions.
    [420] Experimental Example B24 : In vivo effect on infection with mouse hair mites after subcutaneous injection
    [421] Mice infected with ticks (Mucopetes musculinus and Mubia musculin) were anesthetized and the density of the tick community was examined under stereomicroscopy. The mice were divided into groups with the same infection index, ranging from grades 1 (no ticks) to grades 30 (highest tick density), ie, in each case with the same tick population. For testing purposes, only mice with an index of at least 25 grade (high tick density) were used. Test substance was dissolved in a 2: 3 mixture of glycerol formal and polyethylene glycol and injected subcutaneously into test animals. Dosage was 20 to 0.1 mg / kg body weight. Efficacy was measured by comparing the infection index after administration with the infection index after 7 days, 28 days and 56 days after administration. Efficacy is expressed as a decrease in tick population. In this test, Enantiomer A of Formula 1 had a reduction of tick infection rate of 80% or more at a concentration of 0.32 mg / kg (body weight) or less. However, mice did not show skin inflammation and any other unwanted side effects at the site of infection. The resistance to the material was found to be very weak. In contrast, enantiomer B of Formula 1 did not show substantially activity under the same conditions.
    权利要求:
    Claims (14)
    [1" claim-type="Currently amended] Enantiomers of formula (I) in the free form or in the salt form, respectively.
    <Formula 1>

    Where
    X and Y are each independently hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkyl Thio, C 1 -C 4 -haloalkylthio, cyano-C 1 -C 4 -alkyl, cyano-C 1 -C 4 -haloalkyl, cyano-C 1 -C 4 -alkoxy, cyano-C 1 -C 4 -haloalkoxy, cyano-C 1 -C 4 -alkylthio, cyano-C 1 -C 4 -haloalkylthio, halogen, amino, cyano or nitro;
    Z is hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy or di (C 1 -C 4 -alkyl) amino;
    R 1 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkylthio, cyano-C 1 -C 4 -alkyl, cyano-C 1 -C 4 -haloalkyl, cyano-C 1 -C 4 -alkoxy, cyano-C 1 -C 4 -halo Alkoxy, cyano-C 1 -C 4 -alkylthio, cyano-C 1 -C 4 -haloalkylthio, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 - alkenyloxy, C 2 -C 6 - haloalkyl alkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 2 -C 6 - alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 3 -C 8 -cycloalkyl, C 3 -C 8 -halocycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, C 3 -C 8 -halo cycloalkyl, -C 1 -C 4 - alkyl, OC (O) R 3, or halogen;
    R 2 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkylthio or halogen;
    R 3 is C 1 -C 4 - alkyl, C 1 -C 4 - alkoxy, C 2 -C 6 - alkenyl, C 2 -C 6 - alkenyloxy, C 2 -C 6 - alkynyl, C 2 - C 6 - alkynyloxy, C 3 -C 8 - cycloalkyl, C 3 -C 8 - cycloalkyl-oxy, C 3 -C 8 - halocycloalkyl -C 1 -C 4 - alkyl, C 3 -C 8 - Halocycloalkyl-C 1 -C 4 -alkyloxy, N (R 4 R 5 ), unsubstituted phenyl or mono to penta-substituted phenyl, wherein the substituents are C 1 -C 4 -alkyl, C 1 -C 4 -Haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkylthio, halogen, cyano and nitro Selected from);
    R 4 is hydrogen or C 1 -C 4 -alkyl;
    R 5 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 8 -cycloalkyl, C 3 -C 8 -halocycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, C 3 -C 8 -halocycloalkyl-C 1 -C 4 -alkyl, unsubstituted or mono to penta-substituted phenyl, unsubstituted or mono to penta-substituted phenyl-C 1 -C 4 -alkyl, wherein the substituents are each independently selected from the group comprising C 1 -C 4 -alkyl;
    m and n are each independently 0, 1 or 2, and when m or n is 2, R 1 or R 2 may be the same or different from each other.
    [2" claim-type="Currently amended] The enantiomer of claim 1, wherein the optical rotation of α D (589 nm Na D ) in methanol is negative.
    [3" claim-type="Currently amended] Separating the enantiomeric mixture of formula 1 in free or salt form, respectively, and converting the isolated desired enantiomer and / or the glass enantiomer of formula 1 obtained according to this method into a salt, or according to this method A process for the preparation of the enantiomers of formula (I) as defined in claim 1 in the free or salt form, respectively, characterized in that the salts of the enantiomers of formula (I) obtained are converted into free compounds or other salts.
    [4" claim-type="Currently amended] A pesticide containing, as an active ingredient, the substantially pure enantiomer of Formula 1 as an active ingredient in free form or in agrochemically acceptable salt form.
    [5" claim-type="Currently amended] Comprising administering the composition of claim 4 to a pet or to their habitat. How to control pests.
    [6" claim-type="Currently amended] The method of claim 5, wherein the insects and pests belonging to the family of Acarina .
    [7" claim-type="Currently amended] A method of making the composition of claim 4 comprising adding an adjuvant to thoroughly mix and / or grind the active ingredient with the adjuvant (s).
    [8" claim-type="Currently amended] Use of the enantiomer of formula 1 according to claim 1, in the form of a free or agrochemically acceptable salt, for preparing the composition of claim 4.
    [9" claim-type="Currently amended] Use of the composition of claim 8 for controlling pests.
    [10" claim-type="Currently amended] 10. Use according to claim 9 for protecting plant propagation material.
    [11" claim-type="Currently amended] The method according to claim 5, comprising treatment of the propagation material or a place for cultivating the propagation material.
    [12" claim-type="Currently amended] A plant propagation material treated according to the method according to claim 11.
    [13" claim-type="Currently amended] A composition for combating ectoparasites or endoparasites in a human or animal comprising the substantially pure enantiomer of claim 1 and a physiologically acceptable adjuvant.
    [14" claim-type="Currently amended] Use of the substantially pure enantiomer of claim 1 in a method for controlling an external parasite or an internal parasite in a human or animal.
    类似技术:
    公开号 | 公开日 | 专利标题
    US5852012A|1998-12-22|Oxadiazine derivatives
    AU2002234588B2|2005-03-24|Organic compounds
    US6313166B1|2001-11-06|Phenyl acetic acid derivatives as pesticides
    TW561149B|2003-11-11|Pesticides for controlling parasites on warm-blooded animals, intermediates thereof and a process for their preparation
    US6884755B2|2005-04-26|Pesticidal composition
    NL1012526C2|2000-05-16|Pesticide composition that includes emamectin.
    AU2003264288B2|2007-07-12|Organic compounds
    EP0765120B1|2005-12-21|Synergistic compositions comprising lufenuron and profenofos
    AU2002250841B2|2005-03-03|Pharmaceutical composition containing aminoacetonitril compounds and the use thereof for the prepartion of a pharmaceutical composition for the treatment of endoparasitic pests in animals
    AU2002351995B2|2006-08-10|Benzimidazol-or indol-aminoacetonitrile derivatives for parasite control
    CN100527958C|2009-08-19|Use of macrolides in pest control
    US7091371B2|2006-08-15|Aminoacetonitrile derivatives and their use for controlling parasites
    RU2296119C2|2007-03-27|Cyanoacetyl compounds, method for their preparing and their using |, composition and method for control of parasites
    DE60313622T2|2007-12-27|Indazol aminoacetonitrile derivatives with pesticidal effect
    US7521476B2|2009-04-21|Aminoacetonitrile derivatives suitable for controlling parasites
    AU2002345043B2|2006-05-11|Amenoacetonitrile compounds for controlling endoparasites
    ES2202609T3|2004-04-01|Pesticide compositions.
    CN1078045C|2002-01-23|Pesticidal composition
    JP4598052B2|2010-12-15|Use of pyrimidine compounds in the preparation of anthelmintic drugs.
    US7642379B2|2010-01-05|Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals
    JP4303198B2|2009-07-29|N-acylaminoacetonitrile derivatives and their use for controlling parasites
    TWI352693B|2011-11-21|Novel amidoacetonitrile compounds, parasiticidal c
    EP1783114A1|2007-05-09|N-|aryl indole derivatives as pesticides
    US7153814B2|2006-12-26|Amidoacetonitrile derivatives
    DE60013910T2|2005-09-29|Amino-etherocyclylamides as pesticides and antiparasitic active active substances
    同族专利:
    公开号 | 公开日
    BR0009357A|2002-03-05|
    EP1165527A1|2002-01-02|
    AU4290400A|2000-10-16|
    AU767434B2|2003-11-13|
    ZA200107811B|2002-08-23|
    US20020137781A1|2002-09-26|
    RU2233838C2|2004-08-10|
    CA2367508A1|2000-10-05|
    KR100699973B1|2007-03-27|
    CN1345313A|2002-04-17|
    NZ514064A|2004-01-30|
    MXPA01009788A|2002-03-27|
    CA2367508C|2011-04-26|
    JP2002540194A|2002-11-26|
    CN1135225C|2004-01-21|
    WO2000058291A1|2000-10-05|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    1999-03-26|Priority to CH58399
    1999-03-26|Priority to CH0583/99
    2000-03-24|Application filed by 한스 루돌프 하우스, 헨리테 브룬너, 베아트리체 귄터, 노파르티스 아게
    2000-03-24|Priority to PCT/EP2000/002641
    2002-01-30|Publication of KR20020008387A
    2007-03-27|Application granted
    2007-03-27|Publication of KR100699973B1
    优先权:
    申请号 | 申请日 | 专利标题
    CH58399|1999-03-26|
    CH0583/99|1999-03-26|
    PCT/EP2000/002641|WO2000058291A1|1999-03-26|2000-03-24|Pesticidal enantiomer-pure 2,4-disubstituted oxazolines|
    [返回顶部]