WO2008062005A1 - The use of aminoacetonitril compounds in the control of endoparasites in warm- blood animals. - Google Patents

Abstract

The invention relates to the use of aminoacetonitrile compounds of formula (I) wherein A, R4, R5, m, Y1, Y2, Y3, Y4 and Y5 have the significances given in claim 1, in the control of endoparasites, especially helminths, in warm-blooded productive livestock and domestic animals.

Description

THE USE OF AMINOACETONITRIL COMPOUNDS IN THE CONTROL OF ENDOPARASITES IN WARM-BLOOD ANIMALS .

The present invention relates to veterinary compositions comprising as active ingredient a aminoacetonitrile compound of the formula I or an enantiomers thereof, as defined below and to the use of the compounds of the formula I for the preparation of said veterinary compositions and for combating endoparasites in animals, preferably nematodes. Thus the focus of the present invention is on the use of known aminoacetonitrile compounds in the control of endo- and ectoparasites, especially helminths, in and on warm-blooded productive livestock, domestic animals and fishes.

the control of endoparasites, especially helminthes, in warm-blooded productive livestock and domestic animals.

Said active ingredients have the formula

wherein A is hydrogen,

R1 , R2, R3, Ra, Rb, Rc, Rd, Yi, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, Ci-C₆-alkyl, halo-Ci-C₆-alkyl, Ci-Ce-alkoxy, halo-Ci-C₆- alkoxy, CrCe-alkylthio, halo-CrC₆-alkylthio, CrC₆-alkylsulfinyl, halo-CrCe-alkylsulfinyl, C₁- C₆-alkylsulfonyl, halo-Ci-C₆-alkylsulfonyl, di-Ci-C₆-alkylamino and a cyclic moiety M; whereby M is a cyclic moiety selected from the group consisting of unsubstituted or once to three time substituted C₃-C₆-cycloalkyl, phenyl, phenoxy and pyridyloxy, and whereby the substituents are independently of each other selected from the group consisting of halogen, nitro, cyano, d-Ce-alkyl, halo-Ci-C₆-alkyl, Ci-Ce-alkoxy, halo-Ci-C₆-alkoxy, CrC₆-alkylthio, halo-Ci-C₆- alkylthio; or A stands for hetaryl that is unsubstituted or carries one, two or three substituents selected from the group defined for R1 ; R4 and R5 are independently of each other hydrogen, CrC₆-alkyl, or for a saturated C₃-C₆- cycloalkylalkyl, and m is 0, 1 , 2, 3, 4, 5 or 6.

Substituted amidoacetonitrile compounds with pesticidal action are disclosed in EP0953565, for example. The active ingredients specifically revealed therein may not, however, always meet the requirements concerning strength and activity spectrum. There consequently exists a need for active ingredients with improved pesticidal properties. It has now been found that the amidoacetonitrile compounds of the formula I have outstanding pesticidal properties, in particular against endo- and ectoparasites in and on productive livestock, domestic animals fishes and plants.

An important aspect of the present invention is a veterinary composition comprising a compound of the formula I and a physiologically acceptable carrier.

Alkyl - as group per se and as structural component of other groups and compounds, for example of haloalkyl, alkoxy, alkylthio, alkylsulfinyl and alkylsulfonyl, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, either straight-chain, i.e. methyl, ethyl, propyl, butyl, pentyl or hexyl, or branched, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl.

Cycloalkyl - as group per se and as structural component of other groups and compounds, for example of a substituted cycloalkylgroup, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

Aryl is phenyl or naphthyl, preferably phenyl.

Hetaryl is heteroaromatic ring that is bound to the basic molecule through a C-C bond and is selected from the group consisting of pyridyl, pyrimidyl, s-triazinyl, 1 ,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl and indazolyl, preferably from pyridyl, pyrimidyl, s-triazinyl and 1 ,2,4-triazinyl, in particular from pyridyl and pyrimidyl.

Halogen - as group per se and as structural component of other groups and compounds, such as of haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, - is fluorine, chlorine, bromine or iodine, in particular fluorine, chlorine or bromine, especially fluorine or chlorine.

Halogen-substituted carbon-comprising groups and compounds, such as haloalkyl, halo- alkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, can be partially halogenated or perhalogenated, it being possible, in the case of polyhalogenation, for the halogen substituents to be identical or different. Examples of haloalkyl - as group per se and as structural component of other groups and compounds, such as of haloalkoxy or haloalkylthio, - are methyl substituted up to three times by fluorine, chlorine and/or bromine, such as CHF₂ or CF₃; ethyl substituted up to five times by fluorine, chlorine and/or bromine, such as CH₂CF₃, CF₂CF₃, CF₂CCI₃, CF₂CHCI₂, CF₂CHF₂, CF₂CFCI₂, CF₂CHBr₂, CF₂CHCIF, CF₂CHBrF or CCIFCHCIF; propyl or isopropyl substituted up to seven times by fluorine, chlorine and/or bromine, such as CH₂CHBrCH₂Br, CF₂CHFCF₃, CH₂CF₂CF₃ or CH(CF₃)₂; butyl or one of its isomers substituted up to nine times by fluorine, chlorine and/or bromine, such as CF(CF₃)CHFCF₃ or CH₂(CF₂)₂CF₃; pentyl or one of its isomers substituted up to eleven times by fluorine, chlorine and/or bromine, such as CF(CF₃)(CHF)₂CF₃ or CH₂(CF₂)₃CF₃; and hexyl or one of its isomers substituted up to thirteen times by fluorine, chlorine and/or bromine, such as (CH₂)₄CHBrCH₂Br, CF₂(CHF)₄CF₃, CH₂(CF₂)₄CF₃ or C(CF₃)₂(CHF)₂CF₃.

Alkoxy groups preferably have a chain length of 1 to 6 carbon atoms. For example, alkoxy is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, and also the pentyloxy and hexyloxy isomers; preferably methoxy and ethoxy. Haloalkoxy groups preferably have a chain length of 1 to 6 carbon atoms. Haloalkoxy is, e.g., fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2-tetrafluoroethoxy, 2-fluoro- ethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.

Preferred subgroups compounds within the formula I consist of:

(1 ) Compounds of the formula I, wherein R4 and R5 are independently of each other hydrogen or methyl, and the other substituents are as previously defined under formula I.

(2) Compounds of the formula I, wherein A is hydrogen,

- A -

R1 , R2, R3, Ra, Rb, Rc, Rd, Yi, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, Ci-Ce-alkyl, halo-Ci-C₆-alkyl, Ci-Ce-alkoxy, halo-Ci-C₆- alkoxy, Ci-C₆-alkylthio, halo-Ci-C₆-alkylthio, Ci-C₆-alkylsulfinyl and CrC₆-alkylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl, preferably hydrogen; and m is 1 or preferably 0.

(3) Compounds of the formula I, wherein A is

R1 , R2, and R3 independently of each other is hydrogen, chlorine, fluorine, nitro, cyano, methyl, ethyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl; Y₁ , Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, chlorine, fluorine, nitro, cyano, methyl, methoxy, methylthio, trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl, preferably hydrogen; and m is 1 or preferably 0.

(4) Compounds of the formula I, wherein A is

R1 , R2, and R3 independently of each other is hydrogen, cyano, chlorine, fluorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Yi, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl, preferably hydrogen; and m is 0 or 1 .

(5) Compounds of the formula I, wherein A is

R1 , R2, and R3 independently of each other is hydrogen, cyano, chlorine, fluorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Yi, Y₂, Y₃, and Y₅ are hydrogen; Y₄ is trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethyl- sulfonyl; R4 and R5 are independently of each other hydrogen or methyl, preferably hydrogen; and m is 0.

(6) Compounds of the formula I, wherein A is a hetaryl selected from the group consisting of pyridyl, pyrimidyl, s-triazinyl, 1 ,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl and indazolyl, preferably from pyridyl, pyrimidyl, s-triazinyl and 1 ,2,4- triazinyl, in particular from pyridyl and pyrimidyl that is unsubstituted or carries one, two or three substituents selected from the group hydrogen, cyano, chlorine, fluorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy; Yi, Y₂, Y₃, and Y₅ are hydrogen; Y₄ is trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethyl- sulfonyl; R4 and R5 are independently of each other hydrogen or methyl, preferably hydrogen; and m is 0.

The compounds of the formula I listed in Table 1 are particularly preferred within the context of the invention and very particularly those presented with physical pharameters.

A further subject-matter of the invention is the process for the preparation of the compounds of the formula I, which comprises the reaction of a compound of the formula

which is known or can be prepared by analogy to relevant known compounds and in which A, R4, R5 and m are as defined above in the formula I, with a compound of the formula

which is known or can be prepared by analogy to relevant known compounds and in which Yi, Y2, Y₃, Y4 and Y₅ are as defined as in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst.

If desired, one can convert a compound of the formula I obtainable according to this process or in another way, from the free form to a salt form, or to another compound of the formula I. One can also separate the mixture of isomers isolate the desired isomer.

The reactants can be reacted with one another as such, i.e. without addition of a solvent or diluent, e.g. in the molten form. For the most part, however, it is advantageous to add an inert solvent or diluent or a mixture thereof. Mention may be made, as examples of such solvents or diluents, of: aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, such as benzene, toluene, xylene, mesitylene, tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, tetrachloromethane, dichloroethane, trichloroethene or tetrachloroethene; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether, tetrahydrofuran or dioxane; ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone; amides, such as N,N-dimethyl- formamide, N,N-diethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone or hexamethylphosphoramide; nitriles, such as acetonitrile or propionitrile; and sulfoxides, such as dimethyl sulfoxide.

Preferred leaving groups Q are OH, halogens, tosylates, mesylates and triflates, particularly preferably halogens, especially chlorine.

Suitable bases for facilitating the reaction are, e.g., alkali metal or alkaline earth metal hydroxides, hydrides, amides, alkoxides, acetates, carbonates, dialkylamides or alkyl- silylamides, alkylamines, alkylenediamines, if desired N-alkylated and saturated or unsaturated, cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Mention may be made, by way of examples, of sodium hydroxide, sodium hydride, sodamide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-Cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1 ,5-diazabicyclo[5.4.0]undec-5-ene (DBU). The reaction is advantageously carried out at a temperature from approximately O'O to approximately +150⁹C, preferably from approximately 20⁹C to approximately +100⁹C. According to the method or reaction conditions, the compounds I with salt-forming properties can be obtained in the free form or in the form of salts.

The compounds I can also be obtained in the form of their hydrates and/or can incorporate other solvents, which might, for example, be used in the crystallization of compounds existing in the solid form.

The compounds I can exist in the form of one of the possible isomers or as a mixture of the same, e.g., according to the number, absolute and relative configuration of the asymmetric carbon atoms, as pure isomers, for example optical isomers and/or diastereoisomers, or as mixtures of isomers, such as mixtures of enantiomers, e.g. racemates, mixtures of diastereoisomers or racemate mixtures; the invention relates both to the pure isomers and to all possible mixtures of isomers and is to be correspondingly understood in each case heretofore and hereinafter, even if stereochemical details are not specifically referred to in every case.

Mixtures of diastereoisomers and mixtures of racemates of compounds I obtainable according to the process - depending on the choice of the starting materials and operating methods - or otherwise obtainable can be separated in a known way into the pure diastereoisomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.

Correspondingly obtainable mixtures of enantiomers, such as racemates, can be resolved into the optical isomers by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, e.g. high performance liquid chromatography (HPLC) on acetylcellulose, with the help of suitable microorganisms, by cleavage with specific immobilized enzymes, via the formation of inclusion complexes, e.g. by using chiral crown ethers, in which only one enantiomer is complexed.

In addition to through separation of the corresponding mixtures of isomers, pure diastereoisomers or enantiomers according to the invention can also be obtained through generally known methods of diastereoselective or enantioselective synthesis, e.g. by carrying out the process according to the invention with educts with correspondingly suitable stereochemistry.

Advantageously, the biologically more effective isomer, e.g. enantiomer, or mixture of isomers, e.g. mixture of enantiomers, is isolated or synthesized each time, provided that the individual components have different biological activity.

In the process of the present invention, use is preferably made of such starting materials and intermediates which result in the compounds I described at the beginning as particularly valuable. The invention in particular relates to the preparation process described in the example. Starting materials and intermediates used according to the invention for the preparation of the compounds I which are novel, their use and processes for their preparation likewise form a subject-matter of the invention.

In the context of the present invention, ectoparasites are understood to be in particular insects, acari (mites and ticks), and crustaceans (sea lice). These include insects of the following orders: Lepidoptera, Coleoptera, Homoptera, Hemiptera, Heteroptera, Diptera, Dictyoptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Phthiraptera, Thysanura, Isoptera, Psocoptera and Hymenoptera. However reference may in particular be made to ectoparasites which are a nuisance to man or animals and which transmit pathogens, for example flies such as Musca domestica, Musca vetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria, Lucilia cuprina, Lucilia sericata, Hypoderma bovis, Hypoderma lineatum, Chrysomyia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, biting flies such as Haematobia irritans irritans, Haematobia irritans exigua, Stomoxys calcitrans, horse-flies (Tabanids) with the subfamilies of Tabanidae such as Haematopota spp. (e.g. Haematopota pluvialis) and Tabanus spp, (e.g. Tabanus nigrovittatus) and Chrysopsinae such as Chrysops spp. (e.g. Chrysops caecutiens); Hippoboscids such as Melophagus ovinus (sheep ked); tsetse flies, such as Glossinia spp,; other biting insects like midges, such as Ceratopogonidae (biting midges), Simuliidae (Blackflies), Psychodidae (Sandflies); but also blood-sucking insects, for example mosquitoes, such as Anopheles spp, Aedes spp and Culex spp, fleas, such as Ctenocephalides felis and Ctenocephalides canis (cat and dog fleas), Xenopsylla cheopis, Pulex irritans, Ceratophylllus gallinae, Dermatophilus penetrans, blood-sucking lice (Anoplura) such as Linognathus spp, Haematopinus spp, Solenopotes spp, Pediculus humanis; but also chewing lice (Mallophaga) such as Bovicola (Damalinia) ovis, Bovicola (Damalinia) bovis and other Bovicola spp.

Compounds of the formula I can also be used against hygiene pests, especially of the order Diptera of the families Muscidae, Sarcophagidae, Anophilidae and Culicidae; the orders Orthoptera, Dictyoptera (e.g. the family Blattidae (cockroaches), such as Blatella germanica, Blatta orientalis, Periplaneta Americana), Isoptera (termites) and Hymenoptera (e.g. the families Formicidae (ants) and Vespidae (wasps).

The compounds I also have lasting activity in the case of phytoparasitic mites and insects. In the case of spider mites of the order Acarina, they are active against eggs, nymphs and adults of Tetranychidae (Tetranychus spp. and Panonychus spp.). They are highly active in the case of the sucking insects of the order Homoptera, in particular against pests of the families Aphididae, Delphacidae, Cicadellidae, Psyllidae, Loccidae, Diaspididae and Eriophydidae (e.g. citrus rust mite); of the orders Hemiptera, Heteroptera and Thysanoptera, and in the case of the phytophagous insects of the orders Lepidoptera, Coleoptera, Diptera and Orthoptera.

They are also suitable as soil insecticides against pests in the soil. The compounds of the formula I are accordingly active against all development stages of sucking and feeding insects on crops such as cereals, cotton, rice, maize, soya beans, potatoes, vegetables, fruit, tobacco, hops, citrus fruit, avocados and others. Ectoparasites also include members of the order Acarina, such as mites (e.g. Chorioptes bovis, Cheyletiella spp., Dermanyssus gallinae, Demodex canis, Sarcoptes scabiei, Psoroptes ovis and Psorergates spp. and ticks. Known representatives of ticks are, for example, Boophilus, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Ornithodoros and the like, which preferably infest warm-blooded animals including farm animals, such as cattle, horses, pigs, sheep and goats, poultry such as chickens, turkeys, guinea fowls and geese, fur-bearing animals such as mink, foxes, chinchillas, rabbits and the like, as well as domestic animals such as cats and dogs, but also humans.

Ticks may be divided into hard and soft ticks, and are characterized by infesting one, two or three host animals. They attach themselves to a passing host animal and suck the blood or body fluids. Fully engorged female ticks drop from the host animal and lay large amounts of eggs (2000 to 3000) in a suitable crack in the floor or in any other protected site where the larvae hatch. These in turn seek a host animal, in order to suck blood from it. Larvae of ticks which only infest one host animal molt twice and thus become nymphs and finally adult ticks without leaving the host they have selected. Larvae of ticks which infest two or three host animals leave the animal after feeding on the blood, molt in the local environment and seek a second or third host as nymphs or as adult ticks, in order to suck its blood. Ticks are responsible world-wide for the transmission and spread of many human and animal diseases. Because of their economic influence, the most important ticks are Boophilus, Rhipicephalus, Ixodes, Hyalomma, Amblyomma and Dermacentor. They are carriers of bacterial, viral, rickettsial and protozoal diseases and cause tick-paralysis and tick-toxicosis. Even a single tick can cause paralysis whereby its saliva penetrates into the host animal during ingestion. Diseases caused by ticks are usually transmitted by ticks, which infest several host animals. Such diseases, for example babesiosis, anaplasmosis, theileriasis and heart water disease, are responsible for the death or impairment of a large number of domestic and farm animals in the entire world. In many countries of temperate climate, Ixodid ticks transmit the agent of the chronically harmful Lyme's disease from wild animals to humans. Apart from the transmission of disease, the ticks are responsible for great economic losses in livestock production. Losses are not confined to the death of the host animals, but also include damage to the pelts, loss of growth, a reduction in milk production and reduced value of the meat.

The compounds of the formula I according to the invention are also active against all or individual development stages of animal pests showing normal sensitivity, as well as those showing resistance to widely used parasiticides. This is especially true for resistant insects and members of the order Acarina. The insecticidal, ovicidal and/or acaricidal effect of the active substances of the invention can manifest itself directly, i.e. killing the pests either immediately or after some time has elapsed, for example when moulting occurs (growth regulators), or by destroying their eggs, or indirectly, e.g. reducing the number of eggs laid and/or the hatching rate, good efficacy corresponding to a pesticidal rate (mortality) of at least 50 to 60%.

The compounds I also have lasting activity in the case of phytoparasitic mites and insects. In the case of spider mites of the order Acarina, they are active against eggs, nymphs and adults of Tetranychidae (Tetranychus spp. and Panonychus spp.).

They are highly active in the case of the sucking insects of the order Homoptera, in particular against pests of the families Aphididae, Delphacidae, Cicadellidae, Psyllidae, Loccidae,

Diaspididae and Eriophydidae (e.g. citrus rust mite); of the orders Hemiptera, Heteroptera and Thysanoptera, and in the case of the phytophagous insects of the orders Lepidoptera,

Coleoptera, Diptera and Orthoptera.

They are also suitable as soil insecticides against pests in the soil.

The compounds of the formula I are accordingly active against all development stages of sucking and feeding insects on crops such as cereals, cotton, rice, maize, soya beans, potatoes, vegetables, fruit, tobacco, hops, citrus fruit, avocados and others.

The compounds are particularly active against helminths, among which the endoparasitic nematodes and trematodes can be the cause of serious diseases in mammals, fish and poultry, e.g. in sheep, pigs, goats, cattle, horses, donkeys, dogs, cats, guinea pigs, salmonids, cods and ornamental birds. Typical nematodes of this indication are: Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostonum, Oesophagostonum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and

Parascaris. Mention may specifically be made, among the trematodes, of the family of the

Fasciolideae, in particular Fasciola hepatica.

The particular advantage of the compounds of the formula I is their activity against such parasites, which are resistant to benzimidazole-based active ingredients and to macrocyclic lactones.

Certain species of the genera Nematodirus, Cooperia and Oesophagostonum infect the intestinal tract of the host animal, while others of the genera Haemonchus and Ostertagia parasitize in the stomach and others of the genus Dictyocaulus parasitize in lung tissue.

Parasites of the families Filariidae and Setariidae are found in internal cell tissue and in organs, e.g. the heart, blood vessels, lymph vessels and subcutaneous tissue. Mention may particularly be made here of the dog heartworm, Dirofilaria immitis.

The compounds of the formula I are highly effective against these parasites.

The pests which can be controlled with the compounds of the formula I also include, from the class Cestoda (tapeworms), the families Mesocestoidae, in particular the genus

Mesocestoides, especially M. lineatus; Dilepididae, in particular Dipylidium caninum,

Joyeuxiella spp., especially Joyeuxiella pasquali, and Diplopylidium spp.; and Taeniidae, in particular Taenia pisiformis, Taenia cervi, Taenia ovis, Taenia hydatigena, Taenia multiceps,

Taenia taeniaeformis, Taenia serialis and Echinocuccus spp., particularly preferably Taenia hydatigena, Taenia ovis, Taenia multiceps, Taenia serialis; Echinocuccus granulosus,

Echinococcus multilocularis, and Multiceps multiceps.

In a very particularly preferred way, Taenia hydatigena, Taenia pisiformis, Taenia ovis,

Taenia taeniaeformis, Multiceps multiceps, Joyeuxiella pasquali, Dipylidium caninum,

Mesocestoides spp., Echinococcus granulosus and E. multilocularis are controlled simultaneously with Dirofilaria immitis, Ancylostoma spp., Toxocara spp. and/or Trichuris vulpis on or in dogs and cats. Also in a preferred way, Ctenocephalides felis and/or

Ctenocephalides canis are controlled simultaneously with the abovementioned nematodes and cestodes.

The compounds of the formula I are also suitable for controlling parasites which are pathogenic to man, among which may be mentioned, as typical representatives occurring in the digestive tract, those of the genera Ancylostoma, Necator, Ascaris, Strongyloides,

Trichinella, Capillaria, Trichuris and Enterobius. The compounds of the present invention are also active against parasites of the genera Wuchereria, Brugia, Onchocerca and Loa from the family of the Filariidae, which occur in the blood, in tissue and in various organs, and also against Dracunculus and parasites of the genera Strongyloides and Trichinella, which specifically infect the gastrointestinal tract.

The compounds of the formula I are also active against plant nematodes of the genera Meloidogyne, Heterodera, Pratylenchus, Ditylenchus, Radopholus, Rizoglyphus and others.

The compounds of the formula I are used as such or preferably together with the auxiliaries conventional in formulation technology and can accordingly be processed in a known way, for example to liquid formulations such as solutions, suspensions, emulsions, emulsifiable concentrates, dilutable solutions or solid formulations such as soluble powders, granules, tablets, capsules. The application methods as well as the compositions are chosen in accordance with the intended aims and the prevailing circumstances. The formulation, i.e. the compositions, preparations or combinations comprising the active ingredient of the formula I, or combinations of these active ingredients with other active ingredients, and, if desired, a solid or liquid additive, is prepared in a known way, for example by dissolving, intimately mixing and/or grinding the active ingredients with extenders, for example with solvents, solid carriers and other excipients with required properties like surface-active compounds (surfactants), solubilizers, stabilizers, preservatives. Preferred application forms for use in warm-blooded animals for controlling helminths include oral liquid formulations (drenches) such as solutions, emulsions, suspensions, emulsion concentrates, directly dilutable solutions, oral solid formulations such as feed additives, powders, tablets, including effervescent tablets, boluses, capsules, microencapsulations and topically applied pour-on formulations such as solutions, suspensions, emulsions, emulsion concentrates, solution concentrates, and parenterally or subcutaneously administered formulations such as solutions, suspensions, emulsions or long acting parenteral formulations like microparticles, implants or injectable depots; care having to be taken over the physiological compatibility of the formulation auxiliaries.

The following are possible as solvents: alcohols, such as ethanol, propanol or butanol, and glycols, and their ethers and esters, such as propylene glycol, dipropylene glycol ether, ethylene glycol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, ketones, such as cyclohexanone, isophorone or diacetone alcohol, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide or water, vegetable and mineral oils, such as rapeseed oil, castor oil, coconut oil, soybean oil or medium chain triglycerides; and, if desired, silicone oils.

Suitable binders for tablets and boluses are chemically modified polymeric natural products which are soluble in water or alcohol, such as starch, cellulose or protein derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxyethylcellulose, proteins, such as zein, gelatin, and the like), and synthetic polymers, for example polyvinyl alcohol, polyvinylpyrrolidone, and the like. Tablets also comprise fillers (e.g., starch, microcrystalline cellulose, sugar, lactose, and the like), glidants, lubricants and disintegrating agents. If the anthelmintic compositions are present in the form of feed concentrates, then high- performance feed, feed cereals or protein concentrates, for example, are used as carriers. Such feed concentrates or compositions can, in addition to the active ingredients, also comprise additives, vitamins, antibiotics, chemotherapeutics, or other pesticides, mainly bacteriostats, fungistats, coccidiostats, or also hormone preparations, anabolics or substances which promote growth, influence the quality of meat from animals for slaughter or are useful to the organism in another way. If the compositions or the active ingredients of the formula I present therein are added directly to the feed or to the drinking water for the animals, the finished feed or the finished drinking water comprises the active ingredients preferably in a concentration from approximately 0.0005 to 0.02% by weight (5-200 ppm).

The compounds of the formula I according to the invention can be used alone or in combination with other biocides. They can, e.g., be combined with pesticides possessing the same direction of action, in order to enhance the action, or can be combined with substances possessing another direction of action, in order to broaden the activity spectrum. It may also make sense to add substances which repel, known as repellents. If it is desired to expand the activity spectrum with regard to endoparasites, for example worms, the compounds of the formula I are appropriately combined with substances having endoparasiticidal properties. They can also, naturally, be used in combination with antibacterial compositions. Since the compounds of the formula I represent adulticides, i.e. since they are effective in particular against the adult stages of the target parasites, the addition of pesticides which are more likely to attack the juvenile stages of parasites can be highly advantageous. In this way, most of those parasites causing great economic damage are namely included. In addition, a substantial contribution is also made as well to avoiding the formation of resistance. Some combinations can also lead to synergistic effects, i.e. that the total amount of active substance consumed can be reduced, which is desirable from an ecological viewpoint. Preferred groups of combination participants and particularly preferred combination participants are mentioned subsequently, which combinations can, in addition to a compound of the formula I, comprise one or more of these participants.

Suitable participants in the mixture include biocides, for example the insecticides and acaricides with different mechanisms of action mentioned subsequently and sufficiently known to a person skilled in the art, for example chitin synthesis inhibitors, growth regulators; active ingredients which act as juvenile hormones; active ingredients which act as adulticides; broad spectrum insecticides, broad spectrum acaricides and nematicides; but also the sufficiently known anthelmintics and substances which repel insects and/or members of the Acarina, known as repellents or detachers. Nonlimiting examples of suitable insecticides and acaricides are:

1. Abamectin 29. Carbaryl 57. Dioxathion

2. AC 303 630 30. Carbofuran 58. DPX-MP062

3. Acephate 31 . Carbophenothion 59. Edifenphos

4. Acrinathrin 32. Cartap 60. Emamectin

5. Alanycarb 33. Cloethocarb 61 . Endosulfan

6. Aldicarb 34. Chlorethoxyfos 62. Esfenvalerate

7. -Cypermethrin 35. Chlorfenapyr 63. Ethiofencarb

8. Alphamethrin 36. Chlorfluazuron 64. Ethion

Amitraz 37. Chlormephos 65. Ethofenprox

10. Avermectin B₁ 38. Chlorpyrifos 66. Ethoprophos

1 1. AZ 60541 39. Cis-Resmethrin 67. Etrimfos

12. Azinphos E 40. Clocythrin 68. Fenamiphos

13. Azinphos-methyl 41 . Clofentezine 69. Fenazaquin

14. Azocyclotin 42. Cyanophos 70. Fenbutatin oxide

15. Bacillus subtil, toxin 43. Cycloprothrin 71 . Fenitrothion

16. Bendiocarb 44. Cyfluthrin 72. Fenobucarb

17. Benfuracarb 45. Cyhexatin 73. Fenothiocarb

18. Bensultap 46. D 2341 74. Fenoxycarb

19. -Cyfluthrin 47. Deltamethrin 75. Fenpropathrin

20. Bifenthrin 48. Demeton M 76. Fenpyrad

21. BPMC 49. Demeton S 77. Fenpyroximate

22. Brofenprox 50. Demeton-S-methyl 78. Fenthion

23. Bromophos E 51 . Dichlofenthion 79. Fenvalerate

24. Bufencarb 52. Dicliphos 80. Fipronil

25. Buprofezin 53. Diethion 81 . Fluazinam

26. Butocarboxim 54 Diflubenzuron 82. Fluazuron

27. Butylpyridaben 55 Dimethoate 83. Flucycloxuron

28. Cadusafos 56 Dimethylvinphos 84. Flucythrinate 85. Flufenoxuron 1 17. Milbemectin 150. RH-5992

86. Flufenprox 1 18. Moxidectin 151. RH-2485

87. Fonofos 1 19. Naled 152. Salithion

88. Formothion 120. NC 184 153. Sebufos

89. Fosthiazate 121. NI-25, Acetamiprid 154. Silafluofen

90. Fubfenprox 122. Nitenpyram 155. Spinosad

91. HCH 123. Omethoate 156. Sulfotep

92. Heptenophos 124. Oxamyl 157. Sulprofos

93. Hexaflumuron 125. Oxydemeton M 158. Tebufenozide

94. Hexythiazox 126. Oxydeprofos 159. Tebufenpyrad

95. Hydroprene 127. Parathion 160. Tebupirimfos

96. lmidacloprid 128. Parathion-methyl 161. Teflubenzuron

97. Insect-active fungi 129. Permethrin 162. Tefluthrin

98. Insect-active 130. Phenthoate 163. Temephos nematodes 131. Phorate 164. Terbam

99. Insect-active viruses 132. Phosalone 165. Terbufos

100 . lprobenfos 133. Phosmet 166. Tetrachlorvinphos

101 . lsofenphos 134. Phoxim 167. Thiafenox

102 . lsoprocarb 135. Pirimicarb 168. Thiodicarb

103 . Isoxathion 136. Pirimiphos E 169. Thiofanox

104 . Ivermectin 137. Pirimiphos M 170. Thionazin

105 . -Cyhalothrin 138. Promecarb 171. Thuringiensin

106 . Lufenuron 139. Propaphos 172. Tralomethrin

107 . Malathion 140. Propoxur 173. Triarathene

108 . Mecarbam 141. Prothiofos 174. Triazamate

109 . Mesulfenfos 142. Prothoate 175. Triazophos

1 10 . Metaldehyde 143. Pyraclofos 176. Triazuron

1 1 1 . Methamidophos 144. Pyridaphenthion 177. Trichlorfon

1 12 . Methiocarb 145. Pyresmethrin 178. Triflumuron

1 13 . Methomyl 146. Pyrethrum 179. Trimethacarb

1 14 . Methoprene 147. Pyridaben 180. Vamidothion

115 . Metolcarb 148. Pyrimidifen 181.XMC (3,5-xylyl

1 16 . Mevinphos 149. Pyriproxyfen methylcarbamate) 182.Xylylcarb

183. Yl 5301/5302

184. -Cypermethrin

185.Zetamethrin

Nonlimiting examples of suitable anthelmintics are mentioned subsequently, in which some representatives, in addition to the anthelmintic activity, also have an insecticidal and acaricidal activity and are already included in the above list: (AD Praziquantel = 2-Cyclohexylcarbonyl-4-oxo-1 ,2,3,6,7,1 1 b-hexahydro-4H-pyrazino[2,1 - α]isoquinoline (A2) Closantel = 3,5-Diiodo-N-[5-chloro-2-methyl-4-(α-cyano-4-chlorobenzyl)phenyl]- salicylamide

(A3) Triclabendazole = 5-Chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1 H-benzimidazole (A4) Levamisole = /.-(-)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1 -b]thiazole (A5) Mebendazole = Methyl 5-benzoyl-1 H-benzimidazol-2-ylcarbamate (A6) Omphalotin = a macrocyclic fermentation product from the fungus Omphalotus olearius disclosed in WO 97/20857 (A7) Abamectin = Avermectin B1 (A8) Ivermectin = 22,23-Dihydroavermectin B1 (A9) Moxidectin = 5-0-Demethyl-28-deoxy-25-(1 ,3-dimethyl-1 -butenyl)-6,28-epoxy-23-

(methoxyimino)milbemycin B

(A10) Doramectin = 25-Cyclohexyl-5-0-demethyl-25-de(1 -methylpropyl)avermectin A1 a (A1 1 ) Milbemectin = Mixture of Milbemycin A3 and Milbemycin A4 (A12) Milbemvcin oxime = 5-Oxime of Milbemectin

Nonlimiting examples of suitable repelling substances (repellents or detachers) are: (RD DEET (N,N-Diethyl-m-toluamide)

(R2) KBR 3023 N-Butyl-2-oxycarbonyl-2-(2-hydroxyethyl)piperidine (R3) Cvmiazole = N-2,3-Dihydro-3-methyl-1 ,3-thiazol-2-ylidene-2,4-xylidine The participants in the mixture which are mentioned are very well known to a person skilled in the art. Most are described in the various editions of The Pesticide Manual, The British Crop Protection Council, London, others in the various editions of The Merck Index, Merck & Co. Inc., Rahway, New Jersey, USA, or in the patent literature. The following listing is accordingly restricted to a few references by way of examples.

(I) 2-Methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime (Aldicarb), from The Pesticide Manual, 13^th Ed. (200D, The British Crop Protection Council, London, page 26;

(II) S-(3,4-Dihydro-4-oxobenzo[c(|[1 ,2,3]triazin-3-ylmethyl) 0,0-dimethyl phosphorodithioate (Azinphos-methyl), from The Pesticide Manual, 13^th Ed. (200D, The British Crop Protection Council, London, page 67; Ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N- isopropyl-β-alaninate (Benfuracarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 96;

(IV) 2-Methylbiphenyl-3-ylmethyl (Z)-(I f?S)-c/s-3-(2-chloro-3,3,3-trifluoroprop-1 -enyl)-2,2- dimethylcyclopropanecarboxylate (Bifenthrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 18;

(V) 2-tert-Butylimino-3-isopropyl-5-phenyl-1 ,3,5-thiadiazinan-4-one (Buprofezin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 157;

(VI) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (Carbofuran), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 186;

(VII) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate (Carbosulfan), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 188;

(VIII) S,S'-(2-Dimethylaminotrimethylene) bis(thiocarbamate) (Cartap), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 193;

(IX) 1 -[3,5-Dichloro-4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenyl]-3-(2,6-difluorobenzoyl)- urea (Chlorfluazuron), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 213;

(X) O,O-Diethyl 0-3,5,6-trichloro-2-pyridyl phosphorothioate (Chlorpyrifos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 235;

(XI) (f?S)-α-Cyano-4-fluoro-3-phenoxybenzyl (1 f?S,3f?S;1 f?S,3f?S)-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropanecarboxylate (Cyfluthrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 293;

(XII) Mixture of (S)-α-cyano-3-phenoxybenzyl (Z)-(I f?,3f?)-3-(2-chloro-3, 3, 3-trifluoro- propenyl)-2,2-dimethylcyclopropanecarboxylate and (f?)-α-cyano-3-phenoxybenzyl (Z)- (1 S,3S)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate (Lambda-Cyhalothrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 300;

(XIII) Racemate consisting of (S)-α-cyano-3-phenoxybenzyl (1 f?,3f?)-3-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropanecarboxylate and (f?)-α-cyano-3-phenoxybenzyl (1 S,3S)-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (Alpha-cypermethrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 308; (XIV) A mixture of the stereoisomers of (S)-α-cyano-3-phenoxybenzyl (1 f?S,3f?S,1 RS,3RS)- 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (zeta-Cypermethrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 314;

(XV) (S)-α-Cyano-3-phenoxybenzyl (1 f?,3f?)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane- carboxylate (Deltamethrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 344;

(XVI) 1 -(4-Chlorophenyl)-3-(2,6-difluorobenzoyl)urea (Diflubenzuron), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 395;

(XVII) (1 ,4,5,6, 7,7-Hexachloro-8, 9,10-trinorborn-5-en-2,3-ylenebismethylene) sulfite (Endosulfan), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 459;

(XVIII) α-Ethylthio-o-tolyl methylcarbamate (Ethiofencarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 479;

(XIX) O,O-Dimethyl 0-4-nitro-m-tolyl phosphorothioate (Fenitrothion), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 514;

(XX) 2-sec-Butylphenyl methylcarbamate (Fenobucarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 516;

(XXI) (f?S)-α-Cyano-3-phenoxybenzyl (f?S)-2-(4-chlorophenyl)-3-methylbutyrate (Fenvalerate), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 539;

(XXII) S-[Formyl(methyl)carbamoylmethyl] 0,0-dimethyl phosphorodithioate (Formothion), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 625;

(XXIII) 4-Methylthio-3,5-xylyl methylcarbamate (Methiocarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 813;

(XXIV) 7-Chlorobicyclo[3.2.0]hepta-2,6-dien-6-yl dimethyl phosphate (Heptenophos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 670;

(XXV) 1 -(6-Chloro-3-pyridylmethyl)-Λ/-nitroimidazolidin-2-ylideneamine (Imidacloprid), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 706;

(XXVI) 2-lsopropylphenyl methylcarbamate (Isoprocarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 729; (XXVII) O,S-Dimethyl phosphoramidothioate (Methamidophos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 808;

(XXVIII) S-Methyl Λ/-(methylcarbamoyloxy)thioacetimidate (Methomyl), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 815;

(XXIX) Methyl 3-(dimethoxyphosphinoyloxy)but-2-enoate (Mevinphos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 844;

(XXX) 0,0-Diethyl O-4-nitrophenyl phosphorothioate (Parathion), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 926;

(XXXI) 0,0-Dimethyl O-4-nitrophenyl phosphorothioate (Parathion-methyl), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 928;

(XXXII) S-6-Chloro-2,3-dihydro-2-oxo-1 ,3-benzoxazol-3-ylmethyl 0,0-diethyl phosphoro- dithioate (Phosalone), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 963;

(XXXIII) 2-Dimethylamino-5,6-dimethylpyrimidin-4-yl dimethylcarbamate (Pirimicarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 985;

(XXXIV) 2-lsopropoxyphenyl methylcarbamate (Propoxur), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1036;

(XXXV) 1 -(3,5-Dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea (Teflubenzuron), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 158;

(XXXVI) S-tert-Butylthiomethyl 0,0-diethyl phosphorodithioate (Terbufos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 165;

(XXXVII) Ethyl (3-tert-butyl-1 -dimethylcarbamoyl-1 H- 1 ,2,4-triazol-5-ylthio)acetate, (Triazamate), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1224;

(XXXVIII) Abamectin, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 3;

(XXXIX) 2-sec-Butylphenyl methylcarbamate (Fenobucarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 516;

(XL) Λ/-te/t-Butyl-/V-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide (Tebufenozide), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 147; (XLI) (±)-5-Amino-1 -(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethylsulfinylpyrazole-

3-carbonitrile (Fipronil), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop

Protection Council, London, page 545; (XLII) (flS)-α-Cyano-4-fluoro-3-phenoxybenzyl (1 flS,3flS;1 flS,3Sfl>3-(2,2-dichlorovinyl)-

2,2-dimethylcyclopropanecarboxylate (beta-Cyfluthrin), from The Pesticide Manual,

1 1^thEd. (1997), The British Crop Protection Council, London, page 295; (XLIII) (4-Ethoxyphenyl)[3-(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane (Silafluofen), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 105; (XLIV) te/t-Butyl (£)-α-(1 ,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy)-p-toluate

(Fenpyroximate), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection

Council, London, page 530; (XLV) 2-te^Butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2/-/)-one (Pyridaben), from

The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 161 ; (XLVI) 4-[[4-(1 ,1 -Dimethylethyl)phenyl]ethoxy]quinazoline (Fenazaquin), from The Pesticide

Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 507; (XLVII) 4-Phenoxyphenyl (f?S)-2-(2-pyridyloxy)propyl ether (Pyriproxyfen), from The

Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1073; (XLVIII) 5-Chloro-Λ/-{2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl}-6-ethylpyrimidin-4- amine (Pyrimidifen), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop

Protection Council, London, page 1070; (XLIX) (£)-Λ/-(6-Chloro-3-pyridylmethyl)-Λ/-ethyl-/V-methyl-2-nitrovinylidenediamine

(Nitenpyram), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection

Council, London, page 880; (L) (^-^-[(θ-Chloro-S-pyridyOmethyll-Λ^-cyano-Λ/^methylacetamidine (NI-25, Acetamiprid), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 9; (Ll) Avermectin B₁, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection

Council, London, page 3; (LII) An insect-active extract from a plant, in particular (2f?,6aS, 12aS)-1 ,2,6,6a, 12, 12a- hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4-/?]furo[2,3-/?]chromen-6-one

(Rotenone), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1097; and an extract from Azadirachta indica, in particular azadirachtin, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 59;

(LIII) A preparation comprising insect-active nematodes, preferably Heterorhabditis bacteriophora and Heterorhabditis megidis, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 671 ; Steinernema feltiae, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 1 15, and Steinernema scapterisci, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1 1 16;

(LIV) A preparation obtainable from Bacillus subtilis, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 72; or from a Bacillus thuringiensis strain except for compounds isolated from GC91 or from NCTC1 1821 ; The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 73;

(LV) A preparation comprising insect-active fungi, preferably Verticillium lecanii, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1266; Beauveria brogniartii, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 85; and Beauveria bassiana, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 83;

(LVI) A preparation comprising insect-active viruses, preferably Neodipridon Sertifer NPV, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1342; Mamestra brassicae NPV, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 759; and Cydia pomonella granulosis virus, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 291 ;

(CLXXXI) /V-tert-Butyl-Λ/-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzohydrazide (RH- 2485, Methoxyfenozide), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1094;

(CLXXXII) lsopropyl Λ/-[4-methoxybiphenyl-3-yl]hydrazinecarboxylate (D 2341 ), from Brighton Crop Protection Conference, 1996, 487- 493; and

(R2) Book of Abstracts, 212th ACS National Meeting, Orlando, FL, August 25-29 (1996), AGRO-020. Publisher: American Chemical Society, Washington, D. C. CONEN: 63BFAF.

As a consequence of the above details, a further essential aspect of the present invention relates to combination preparations for the control of parasites on warm-blooded animals, characterised in that they contain, in addition to a compound of formula I, at least one further active ingredient having the same or different sphere of activity and at least one physiologically acceptable carrier. The present invention is not restricted to two-fold combinations.

Especially preferred combination partners for the compounds of the formula I of the present inventions are the more modern natural or chemically modified macrocyclic lactones (macrolides), such as avermectins, milbemycins and derivatives thereof, including prominent representatives such as Ivermectin, Doramectin, Moxidectin, Selamectin, Emamectin, Eprinomectin, Milbemectin, Abamectin, Milbemycin oxime, Nemadectin, and a derivative thereof, in the free form or in the form of a physiologically acceptable salt. The combination of these two different classes of compounds leads to several advantageous effects. In the first instant, one observes a broadening of the activity spectrum with regard to the endo-parasites. The combination product is highly active against all sorts of commercially important worms and, what is really surprising, also against metabolic active larval stages. Investigations concerning arrested larval stages are still ongoing but it could well turn out that the combination product will also be effective against these stages.

A further advantage of the combination product is the pest resistance management, meaning that the occurrence of resistance against the compounds of the formula I can drastically be delayed by the administration of the combination product instead of applying the compounds of formula I only. Another advantage is that the combination product can successfully be used even in those cases where the worm population has already developed resistance against a macrocyclic lactones.

Beyond this, a major advantage of the compounds of the formula I is their exhibiting full efficacy against worms resistant to commonly used products such as representatives of the macrocyclic lactones, e.g. Ivermectin or Moxidectin, and to Levamisole or representatives of the benzimidazole class of anthelmintics.

The macrocyclic lactones are most preferred because they exhibit a broad spectrum of activity. Most of them exhibit ecto- and in parallel endo-parsiticidal activity. Therefore, they are also called endectocides. Macrocyclic lactones bind to glutamated chlorine channels causing paralysis of the parasites in the first instance, followed by their death. Especially preferred combination partners are Ivermectin, Abamectin and Moxidectin. The anthelmintic compositions according to the invention generally comprise 0.1 to 99% by weight, in particular 1 to 95% by weight, of active ingredient of the formula I or mixtures thereof, and 99.9 to 1 % by weight, in particular 99 to 5% by weight, of solid or liquid additives The compositions according to the invention can be applied topically, perorally, parenterally or subcutaneously to the animals to be treated. The compositions include topically applied pour-on formulations such as solutions, suspensions, emulsions, emulsion concentrates, solution concentrates; oral liquid formulations (drenches) such as solutions, emulsions, suspensions, emulsion concentrates, directly dilutable solutions; oral solid formulations such as feed additives, powders, tablets, including effervescent tablets, boluses, capsules, microencapsulations and parenterally or subcutaneously administered formulations such as solutions, suspensions, emulsions or long acting parenteral formulations like microparticles, implants or injectable depots; care having to be taken over the physiological compatibility of the formulation auxiliaries.

The pour-on or spot-on method consists in applying the compound of the formula I to a locally restricted part of the skin or fur, advantageously on the neck or back of the animal. This is carried out, e.g., by applying a spot or dash of the pour-on or spot-on formulation to a relatively small area of the fur, from where the active substance spreads out virtually unaided over wide regions of the fur because of the spreading components of the formulation and supported by the movements of the animal.

It is advantageous for pour-on or spot-on formulations to comprise carriers which promote speedy distribution on the surface of the skin or in the fur of the host animal and which are generally described as spreading oils. Suitable carriers are, e.g., oily solutions; alcoholic and isopropanolic solutions, for example solutions of 2 octyldodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids, such as isopropyl myristate, isopropyl palmitate, lauric acid oxal ester, oleyl oleate, decyl oleate, hexyl laurate, capric acid esters of saturated fatty alcohols with a chain length of C12 C18; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate, diisopropyl adipate or di(n-butyl) adipate, or also solutions of esters of aliphatic acids, e.g. glycols. It can be advantageous if a dispersant known from the pharmaceutical or cosmetics industry is additionally present. Examples are 2 pyrrolidone, 2 (N-alkyl)pyrrolidone, acetone, polyethylene glycol and ethers and esters thereof, propylene glycol or synthetic triglycerides.

The oily solutions include, e.g., vegetable oils, such as olive oil, groundnut oil, sesame oil, pine oil, linseed oil or castor oil. The vegetable oils can also be present in epoxidized form. Paraffin oils and silicone oils can also be used.

In general, a pour-on or spot-on formulation comprises 1 to 20% by weight of a compound of the formula I, 0.1 to 50% by weight of dispersant and 45 to 98.9% by weight of solvent. The pour-on or spot-on method can be used particularly advantageously with gregarious animals, such as cattle, horses, sheep or pigs, where it is difficult or time-consuming to treat all the animals orally or via injection. Because of its simplicity, this method can naturally also be used with all other animals, including individual domestic animals or pets, and is very popular with animal owners because it can often be implemented without the expert assistance of a veterinary surgeon.

While concentrated compositions are more preferred as commercially available products, the end user generally uses dilute compositions.

Such compositions can comprise yet further additives, such as stabilizers, antifoaming agents, viscosity regulators, binders, deposit builders and other active ingredients to obtain specific effects.

Such anthelmintic compositions used by the end user likewise form part of the present invention.

In each of the methods according to the invention for controlling pests or of the pesticides according to the invention, the active ingredients of the formula I can be used in all their steric configurations or mixtures thereof.

The invention also includes a method for the prophylactic protection of warm-blooded animals, in particular of productive livestock, domestic animals and pets, against parasitic helminths, which comprises applying the active ingredients of the formula I or the active ingredient formulations prepared therefrom as a feed additive or drinking water additive or also in the solid or liquid form, orally, by injection or parenterally, to the animals. The invention also includes the compounds of the formula I according to the invention for use in one of the methods mentioned.

The following examples serve merely to illustrate the invention, without limiting it, the term

"active ingredient" represents a substance listed in Table 1 , for example compound No. 29.

Preferred formulations are in particular composed in the following way:

(% = per cent by weight)

Formulation examples

1. Granules a) b)

Active ingredient 5% 10%

Kaolin 94% -

Highly dispersed silica 1 % _

Attapulgite - 90% The active ingredient is dissolved in methylene chloride and sprayed onto the carrier, and the solvent is subsequently evaporated under reduced pressure. Such granules can be added to the animal feed.

2. Granules

Active ingredient 3%

Polyethylene glycol (MW 200) 3%

Kaolin 94%

(MW = molecular weight)

The finely milled active ingredient is applied evenly in a mixer to the kaolin, which has been moistened with polyethylene glycol. In this way, dust-free coated granules are obtained.

3. Tablets or Boluses

I Active ingredient 33.00% Methylcellulose 0.80% Highly dispersed silica 0.80% Maize starch 8.40%

II Cryst. lactose 22.50% Maize starch 17.00% Microcryst. cellulose 16.50% Magnesium stearate 1 .00%

I Methylcellulose is stirred into water. After the material has swollen, silica is stirred in and the mixture is homogeneously suspended. Active ingredient and maize starch are mixed. The aqueous suspension is incorporated in this mixture and kneaded to a dough. The substance thus obtained is granulated through a 12 M sieve and dried.

II All 4 auxiliaries are intimately mixed.

III The premixes obtained according to I and Il are mixed and pressed to give tablets or boluses.

4. lniectables

A. Oily vehicle (slow release)

1. Active ingredient 0.1 -1.0 g Groundnut oil ad 100 ml

2. Active ingredient 0.1 -1.0 g Sesame oil ad 100 ml

Preparation: The active ingredient is dissolved in a portion of the oil with stirring and, if desired, gentle heating, made up to the required volume after cooling and sterilely filtered through a suitable membrane filter with a size of 0.22 m. B. Water-miscible solvent (medium release rate)

1. Active ingredient 0.1 -1.O g 4-Hydroxymethyl-1 ,3-dioxolane (glycerol formal) 40 g 1 ,2-Propanediol ad 100 ml

2. Active ingredient 0.1 -1.O g Glycerol dimethyl acetal 40 g 1 ,2-Propanediol ad 100 ml

Preparation: The active ingredient is dissolved in a portion of the solvent with stirring, made up to the required volume and sterilely filtered through a suitable membrane filter with a size of 0.22 m.

C. Aqueous solubilisate (rapid release)

1. Active ingredient 0.1 -1.0 g Polyethoxylated castor oil (40 ethylene oxide units) 10 g 1 ,2-Propanediol 2O g Benzyl alcohol 1 g Water for injections ad 100 ml

2. Active ingredient 0.1 -1 .0 g Polyethoxylated sorbitan monooleate (20 ethylene oxide units) 8 g 4-Hydroxymethyl-1 ,3-dioxolane (glycerol formal) 20 g Benzyl alcohol 1 g Water for injections ad 100 ml

Preparation: The active ingredient is dissolved in the solvents and the surfactant and made up to the required volume with water. Sterile filtration is carried out through a suitable membrane filter with a pore diameter of 0.22 m.

5. Pour-on A.

Active ingredient 5 g lsopropyl myristate 10 g lsopropanol ad 100 ml

B.

Active ingredient 2 g

Hexyl laurate 5 g

Triglycerides of medium chain length 15 g

Ethanol ad 100 ml

C.

Active ingredient 2 g

Oleyl oleate 5 g

N-Methylpyrrolidone 40 g lsopropanol ad 100 ml

The aqueous systems can preferably also be used for oral and/or intraruminal administration.

The compositions can also comprise further additives, such as stabilizers, e.g. epoxidized or nonepoxidized vegetable oils (epoxidized coconut oil, rapeseed oil or soybean oil), antifoaming agents, e.g. silicone oil, preservatives, viscosity regulators, binders, deposit builders and fertilizers or other active ingredients to obtain specific effects. Further biologically active substances or additives which are neutral towards the compounds of the formula I and have no adverse effect on the host animal to be treated, and mineral salts or vitamins, can also be added to the compositions described.

6. Spot on

A. active ingredient 10-15 g diethyleneglycol monoethylether ad 100 ml

B active ingredient 10-15 g octyl palmitate 1 O g isopropanol ad 100 ml

C active ingredient 10-15 g isopropanol 20 g benzyl alcohol ad 100 ml

7. Spray on

A. active ingredient 1 g isopropanol 40 g propylene carbonate ad 100 ml

B active ingredient 1 g propylene glycol 1 O g isopropanol ad 100 ml

The aqueous systems may also preferably be used for oral and/or intraruminal application.

The compositions may also contain further additives, such as stabilisers, e.g. where appropriate epoxidised vegetable oils (epoxidised coconut oil, rapeseed oil, or soybean oil); antifoams, e.g. silicone oil, preservatives, viscosity regulators, binders, tackifiers, as well as fertilisers or other active ingredients to achieve special effects.

Further biologically active substances or additives, which are neutral towards the compounds of formula I and do not have a harmful effect on the host animal to be treated, as well as mineral salts or vitamins, may also be added to the described compositions.

The following examples serve to illustrate the invention. They do not limit the invention. The letter 'h' stands for hour. The starting substances used may be produced by methods described in literature or are commercially available.

7. Tablets: (each containing a total of 0.0183 g active ingredient) are prepared as follows: Composition (for 10,000 tablets)

Active ingredient 183.00 g

Lactose 290.80 g

Potato starch 274.70 g

Stearic acid 10.0O g

Talc 217.0O g

Magnesium stearate 2.50 g

Colloidal silica 32.00 g

Ethanol q.s.

A mixture of the active ingredient, the lactose and 274.70 g potato starch is wetted with an ethanolic solution of stearic acid and granulated through a sieve. After drying, the remaining potato starch, the talc, the magnesium stearate, and the colloidal silica are added and the mixture compressed to form tablets of 0.1 g each in weight, which - if so desired - can be scored to allow for a finer adjustment of the dose.

8. Capsules: each containing a total of 0.022 g active ingredient can be prepared as follows: Composition (for 1000 capsules)

Active ingredient 22.00 g

Lactose 249.80 g

Gelatin 2.00 g

Corn starch 10.00 g

Talc 15.0O g

Water q.s.

The active ingredient is mixed with the lactose, the mixture wetted evenly with an aqueous solution of the gelatine and granulated through a sieve with a mesh size of 1.2-1 .5 mm. The granulate is mixed with the dried cornstarch and the talc, and portions of 300 mg are filled into hard gelatine capsules (size 1 ).

The following examples serve to clarify the invention. They do not limit the invention. The symbol 'h' denotes hour. Preparation examples

Example 1 :

N-[1 -Cyano-1 -methyl-2-(4-trifluoromethyl-benzyloxy)-ethyl]-4-trifluoromethoxy-benzamide

a) In 40 ml of water are added 2.22 g of ammonium chloride, 2.04 g of sodium cyanide before adding dropwise 4.62 g of hydroxyaceton over 15 minutes. The reaction mixture is stirred for 19 h at RT, cooled to O⁹C and 4.36 g of sodium bicarbonate and 10 ml of ethylacetate are added. Over 30 minutes are added dropwise a solution of 4.49 g of 4-(trifluoromethoxy)benzylchloride in 10 ml of ethylacetate. The reaction mixture is stirred for 90 minutes at O⁹C and then washed successively with a saturated solution of sodium bicarbonate (2x), with water and with brine. The organic phases are dried on magnesium sulphate, filtered and concentrated. The residue is purified by chromatography to afford 3.97 g of N-(1 -Cyano-2-hydroxy-1 -methyl-ethyl)- 4-trifluoromethoxy-benzamide.

b) 144 mg of N-(1 -Cyano-2-hydroxy-1 -methyl-ethyl)-4-trifluoromethoxy-benzamide are dissolved in 1 ml of THF, a solution of 1 12 mg of potassium tert-butoxyde in 1 ml of THF is added followed by 0.155 ml of 4-(trifluoromethyl)benzyl bromide. The reaction mixture is stirred for an hour and then washed with brine. The organic phase is concentrated and the residue purified by chromatography to afford 78 mg of N-[1 - Cyano-1 -methyl-2-(4-trifluoromethyl-benzyloxy)-ethyl]-4-trifluoromethoxy-benzamide, melting point is 102-103⁰C. Table 1 Compounds of the formula Ia

_CT)

Y_{1 1} Y₂₁ Y₃, and Y₅ are hydrogen, Me stands for methyl

No. A m Y₃ m.p.

1 . 4-CI-C6H4- 0 4-CF3

2. 4-CI-C6H4- 0 4-OCF3

3. 4-CI-C6H4- 0 4-SCF3

4. - 3 4-OCF3

5. 4-MeO-C6H4- 0 4-OCF3

6. 3-MeO-C6H4- 0 4-OCF3 93-94 ^<O

7. 4-CN-C6H4- 0 4-OCF3

8. 3-CN-C6H4- 0 4-OCF3 1 10-1 12'C

2-CN-C6H4- 0 4-OCF3 109-1 1 1 ⁰C

10. 2-CI-C6H4- 0 4-OCF3

1 1 . 3-CI-C6H4- 0 4-OCF3 92-93^

12. 2-CI,4-F-C6H3- 0 4-OCF3 88-90^

13. 2-CF3,4-F-C6H3- 0 4-OCF3 69-70^

14. 3-CF3,4-F-C6H3- 0 4-OCF3 95-96^

15. 3-CF3,2-F-C6H3- 0 4-OCF3 83-84 ^<O

16. 5-CF3,2-F-C6H3- 0 4-OCF3 101 -102'C

17. 5-CF3,3-F-C6H3- 0 4-OCF3 87-89^

18. 4-CF3,3-F-C6H3- 0 4-OCF3 69-70^

19. 2-CF3,5-F-C6H3- 0 4-OCF3 82-84^

20. 2-OCF3-C6H4- 0 4-OCF3 61 -62^

21 . 3-OCF3-C6H4- 0 4-OCF3 76-77^

22. 4-OCF3-C6H4- 0 4-OCF3 1 10-1 12'C

23. 4-F-C6H4- 0 4-OCF3 100-101 ⁰C

24. 3-F-C6H4- 0 4-OCF3 88-89^

25. 2-F-C6H4- 0 4-OCF3 106-108⁰C 26. 4-MΘ-C6H4- 0 4-OCF3 120-121 ^<O

27. 3-MΘ-C6H4- 0 4-OCF3 90-91 ⁰C

28. 2-MΘ-C6H4- 0 4-OCF3 121 -123^<O

29. 4-CF3-C6H4- 0 4-OCF3 102-103⁰C

30. 3-CF3-C6H4- 0 4-OCF3 77-79^C

31. 2-CF3-C6H4- 0 4-OCF3 73-74 ^<O

32. 4-MeO-C6H4- 0 4-CF3

33. 3-MeO-C6H4- 0 4-CF3

34. 4-CN-C6H4- 0 4-CF3

35. 3-CN-C6H4- 0 4-CF3

36. 2-CN-C6H4- 0 4-CF3

37. 2-CI-C6H4- 0 4-CF3

38. 3-CI-C6H4- 0 4-CF3

39. 2-CI,4-F-C6H3- 0 4-CF3

40. 2-CF3,4-F-C6H3- 0 4-CF3

41. 3-CF3,4-F-C6H3- 0 4-CF3

42. 3-CF3,2-F-C6H3- 0 4-CF3

43. 5-CF3,2-F-C6H3- 0 4-CF3

44. 5-CF3,3-F-C6H3- 0 4-CF3

45. 4-CF3,3-F-C6H3- 0 4-CF3

46. 2-CF3,5-F-C6H3- 0 4-CF3

47. 2-OCF3-C6H4- 0 4-CF3

48. 3-OCF3-C6H4- 0 4-CF3

49. 4-OCF3-C6H4- 0 4-CF3

50. 4-F-C6H4- 0 4-CF3

51. 3-F-C6H4- 0 4-CF3

52. 2-F-C6H4- 0 4-CF3

53. 4-MΘ-C6H4- 0 4-CF3

54. 3-MΘ-C6H4- 0 4-CF3

55. 2-MΘ-C6H4- 0 4-CF3

56. 4-CF3-C6H4- 0 4-CF3

57. 3-CF3-C6H4- 0 4-CF3

58. 2-CF3-C6H4- 0 4-CF3

59. 4-MeO-C6H4- 0 4-SCF3 60. 3-MeO-C6H4- 0 4-SCF3

61. 4-CN-C6H4- 0 4-SCF3

62. 3-CN-C6H4- 0 4-SCF3

63. 2-CN-C6H4- 0 4-SCF3

64. 2-CI-C6H4- 0 4-SCF3

65. 3-CI-C6H4- 0 4-SCF3

66. 2-CI,4-F-C6H3- 0 4-SCF3

67. 2-CF3,4-F-C6H3- 0 4-SCF3

68. 3-CF3,4-F-C6H3- 0 4-SCF3

69. 3-CF3,2-F-C6H3- 0 4-SCF3

70. 5-CF3,2-F-C6H3- 0 4-SCF3

71. 5-CF3,3-F-C6H3- 0 4-SCF3

72. 4-CF3,3-F-C6H3- 0 4-SCF3

73. 2-CF3,5-F-C6H3- 0 4-SCF3

74. 2-OCF3-C6H4- 0 4-SCF3

75. 3-OCF3-C6H4- 0 4-SCF3

76. 4-OCF3-C6H4- 0 4-SCF3

77. 4-F-C6H4- 0 4-SCF3

78. 3-F-C6H4- 0 4-SCF3

79. 2-F-C6H4- 0 4-SCF3

80. 4-MΘ-C6H4- 0 4-SCF3

81. 3-MΘ-C6H4- 0 4-SCF3

82. 2-MΘ-C6H4- 0 4-SCF3

83. 4-CF3-C6H4- 0 4-SCF3

84. 3-CF3-C6H4- 0 4-SCF3

85. 2-CF3-C6H4- 0 4-SCF3

Bioloqical examples

1. Activity in vitro against Haemonchus contortus & Trichostronqylus colubriformis (Gastrointestinal nematodes).

Freshly harvested and cleaned nematode eggs are used to seed a suitably formatted 96-well plate containing the test substances to be evaluated for antiparasitic activity. Each compound is tested by serial dilution in order to determine its MED. The test compounds are embedded in an agar-based nutritive medium allowing the full development of eggs through to 3rd instar larvae. The plates are incubated for 6 days at 25 °C and 60% relative humidity (RH). Egg- hatching and ensuing larval development are recorded to identify a possible nematicidal activity. Efficacy is expressed in percent reduced egg hatch, reduced development of L3, or paralysis & death of larvae of all stages. In above HTS assay (5.), a given compound has to exhibit a nematicidal efficacy of higher than 99% at a concentration of 32 ppm in order to qualify for further testing. This result is achieved by the compounds Nos. 1 , 4, 5, 6, 7, 10, 1 1 , 12, 13, 14, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 .

2. In vivo test against Trichostronqylus colubriformis and Haemonchus contortus in Mongolian qerbils (Meriones unquiculatus) by peroral administration

Six- to eight-week-old Mongolian gerbils are infected, using manufactured feed, with in each case approximately 2 000 larvae of the 3rd stage of T. colubriformis and H. contortus. Six days after infecting, the gerbils are lightly anaesthetized with N₂O and are treated by peroral administration with the test compounds, dissolved in a mixture of 2 parts of DMSO and 1 part of polyethylene glycol (PEG 300), with amounts of 100, 32 and 10 - 0.1 mg/kg. On day 9 (3 days after treating), when most of the H. contortus larvae still existing are in the late 4th stage and most of the T. colubriformis are immature adults, the gerbils are sacrificed in order to count the worms. The activity is calculated in % reduction in the number of worms in each gerbil by comparison with the geometric mean of the number of worms from 8 infected and untreated gerbils. In this test, a large decrease in the nematode infestation is obtained with compounds of the formula I, in particular from Table 1 , more specifically compounds Nos. 1 , 4, 5, 7, 10, 1 1 , 13, 18, 22, 26, 29. The following embodiments A to L are especially preferred within the present invention: A. The use of compounds the formula I

wherein A is hydrogen,

R1 , R2, R3, Ra, Rb, Rc, Rd, Yi, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, CrC₆-alkyl, halo-Ci-C₆-alkyl, d-Ce-alkoxy, halo-Ci-C₆- alkoxy, d-Ce-alkylthio, halo-CrC₆-alkylthio, CrC₆-alkylsulfinyl, halo-d-Ce-alkylsulfinyl, C₁- C₆-alkylsulfonyl, halo-Ci-C₆-alkylsulfonyl, di-Ci-C₆-alkylamino and a cyclic moiety M; whereby M is a cyclic moiety selected from the group consisting of unsubstituted or once to three time substituted C₃-C₆-cycloalkyl, phenyl, phenoxy and pyridyloxy, and whereby the substituents are independently of each other selected from the group consisting of halogen, nitro, cyano, d-Ce-alkyl, halo-Ci-C₆-alkyl, C_rC₆-alkoxy, halo-Ci-C₆-alkoxy, Ci-C₆-alkylthio, 1IaIo-C₁-C₆- alkylthio; or A stands for hetaryl that is unsubstituted or carries one, two or three substituents selected from the group defined for R1 ;

R4 and R5 are independently of each other hydrogen, d-C₆-alkyl, or for a saturated C₃-C₆- cycloalkylalkyl, and m is 0, 1 , 2, 3, 4, 5 or 6, and optionally enantiomers thereof, as such or in combination with at least one suitable carrier in the control of endoparasitic pests in warm-blooded productive livestock and domestic animals or the use of said compounds for the preparation of a veterinary composition. B. Said use of compound of the formula I, whereby in the compound of the formula I, A is

hydrogen,

; R1 , R2, R3, Ra, Rb, Rc, Rd, Y₁, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, Ci-C₆- alkyl, halo-Ci-C₆-alkyl, Ci-Ce-alkoxy, halo-Ci-C₆-alkoxy, Ci-C₆-alkylthio, halo-Ci-C₆-alkylthio, d-Ce-alkylsulfinyl, halo-Ci-C₆-alkylsulfinyl, Ci-Ce-alkylsulfonyl, halo-Ci-C₆-alkylsulfonyl, di- CrCe-alkylamino and a cyclic moiety M; whereby M is a cyclic moiety selected from the group consisting of unsubstituted or once to three time substituted C₃-C₆-cycloalkyl, phenyl, phenoxy and pyridyloxy, and whereby the substituents are independently of each other selected from the group consisting of halogen, nitro, cyano, Ci-Ce-alkyl, halo-Ci-C₆-alkyl, Ci- C₆-alkoxy, halo-CrC₆-alkoxy, CrC₆-alkylthio, halo-CrCe-alkylthio; or A stands for hetaryl that is unsubstituted or carries one, two or three substituents selected from the group defined for R1 ; R4 and R5 are independently of each other hydrogen or methyll, and m is 0, 1 , 2, 3, 4, 5 or 6.

C. Said use of compound of the formula I, whereby in the compound of the formula I, A is hydrogen,

R1 , R2, R3, Ra, Rb, Rc, Rd, Yi, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, Ci-C₆-alkyl, halo-Ci-C₆-alkyl, Ci-Ce-alkoxy, halo-Ci-C₆- alkoxy, Ci-C₆-alkylthio, halo-CrC₆-alkylthio, CrC₆-alkylsulfinyl and CrC₆-alkylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl; and m is 0 or 1. D. Said use of compound of the formula I, whereby in the compound of the formula I, A is

R1 , R2, and R3 independently of each other is hydrogen, chlorine, fluorine, nitro, cyano, methyl, ethyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl; Y₁ , Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, chlorine, fluorine, nitro, cyano, methyl, methoxy, methylthio, trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl, and m is 0 or1. E. Said use of compound of the formula I, whereby in the compound of the formula I, A is

R1 , R2, and R3 independently of each other is hydrogen, cyano, chlorine, fluorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Yi, Y₂, Y3, Y₄ and Y₅ is each independently of each other hydrogen, trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl, and m is 0 or 1 . F. Said use of compound of the formula I, whereby in the compound of the formula I, A is

R1 , R2, and R3 independently of each other is hydrogen, cyano, chlorine, fluorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Yi, Y₂, Y3, and Y₅ are hydrogen; Y₄ is trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are hydrogen, and m is 0.

G. A veterinary composition comprising as active ingredient an aminoacetonitrile compound of the formula I as defined above or an enantiomers thereof and a suitable physiologically acceptable carrier.

H. Said veterinary composition consisting of a solution, emulsion, suspension, feed additive, powder, tablet, bolus, capsule, microencapsule, pour-on, spray-on, spot-on, drench or an injectable formulation.

I. The use of a compound of formula I as defined above in a process for controlling endoparasites on warm-blooded animals.

K. The use of a compound of formula I as defined above in the preparation of a veterinary composition against endoparasites.

L. A method of controlling endoparasites on warm-blooded animals comprising the administration of a pesticidally amount of a compound as defined above to the endoparasite.

Claims

What is claimed is:

1. Use of compounds the formula

wherein A is hydrogen,

R1 , R2, R3, Ra, Rb, Rc, Rd, Yi, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, CrC₆-alkyl, halo-CrC₆-alkyl, d-C₆-alkoxy, 1IaIo-C₁-C₆- alkoxy, Ci-C₆-alkylthio, halo-Ci-C₆-alkylthio, Ci-C₆-alkylsulfinyl, halo-Ci-C₆-alkylsulfinyl, C_r C₆-alkylsulfonyl, halo-Ci-C₆-alkylsulfonyl, di-Ci-C₆-alkylamino and a cyclic moiety M; whereby M is a cyclic moiety selected from the group consisting of unsubstituted or once to three time substituted C₃-C₆-cycloalkyl, phenyl, phenoxy and pyridyloxy, and whereby the substituents are independently of each other selected from the group consisting of halogen, nitro, cyano, d-Ce-alkyl, halo-Ci-C₆-alkyl, Ci-Ce-alkoxy, halo-Ci-C₆-alkoxy, CrC₆-alkylthio, halo-Ci-C₆- alkylthio; or A stands for hetaryl that is unsubstituted or carries one, two or three substituents selected from the group defined for R1 ;

R4 and R5 are independently of each other hydrogen, Ci-Ce-alkyl, or for a saturated C₃-C₆- cycloalkylalkyl, and m is 0, 1 , 2, 3, 4, 5 or 6, and optionally enantiomers thereof, in the control of endoparasitic pests in warm-blooded productive livestock and domestic animals

2. Use according to claim 1 , whereby in the compound of the formula I, A is hydrogen,

R1 , R2, R3, Ra, Rb, Rc, Rd, Yi, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, d-C₆-alkyl, halo-Ci-C₆-alkyl, d-C₆-alkoxy, halo-d-C₆- alkoxy, Ci-C₆-alkylthio, halo-Ci-C₆-alkylthio, Ci-C₆-alkylsulfinyl, halo-Ci-C₆-alkylsulfinyl, C₁- C₆-alky lsu If onyl , halo-Ci-C₆-alkylsulfonyl, di-Ci-C₆-alkylamino and a cyclic moiety M; whereby M is a cyclic moiety selected from the group consisting of unsubstituted or once to three time substituted C₃-C₆-cycloalkyl, phenyl, phenoxy and pyridyloxy, and whereby the substituents are independently of each other selected from the group consisting of halogen, nitro, cyano, d-Ce-alkyl, halo-Ci-C₆-alkyl, Ci-C₆-alkoxy, halo-Ci-C₆-alkoxy, Ci-C₆-alkylthio, halo-d-dr alkylthio; or A stands for hetaryl that is unsubstituted or carries one, two or three substituents selected from the group defined for R1 ;

R4 and R5 are independently of each other hydrogen or methyll, and m is 0, 1 , 2, 3, 4, 5 or 6.

3. Use according to claim 1 , whereby in the compound of the formula I, A is hydrogen,

R1 , R2, R3, Ra, Rb, Rc, Rd, Y₁, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, halogen, nitro, cyano, CrC₆-alkyl, halo-CrC₆-alkyl, d-C₆-alkoxy, HaIo-C₁-C₆- alkoxy, d-Ce-alkylthio, halo-d-C₆-alkylthio, d-C₆-alkylsulfinyl and d-C₆-alkylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl; and m is 0 or 1.

4. Use according to claim 1 , whereby in the compound of the formula I, A is

R1 , R2, and R3 independently of each other is hydrogen, chlorine, fluorine, nitro, cyano, methyl, ethyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl; Y₁ , Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, chlorine, fluorine, nitro, cyano, methyl, methoxy, methylthio, trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl, and m is 0 or1.

5. Use according to claim 1 , whereby in the compound of the formula I, A is

R1 , R2, and R3 independently of each other is hydrogen, cyano, chlorine, fluorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Y₁, Y₂, Y₃, Y₄ and Y₅ is each independently of each other hydrogen, trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are independently of each other hydrogen or methyl, and m is 0 or 1 .

6. Use according to claim 1 , whereby in the compound of the formula I, A is

R1 , R2, and R3 independently of each other is hydrogen, cyano, chlorine, fluorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Yi, Y₂, Y3, and Y₅ are hydrogen; Y₄ is trifluoromethyl, trifluormethoxy, trifluormethylthio, trifluormethylsulfinyl or trifluormethylsulfonyl; R4 and R5 are hydrogen, and m is 0.

7. Veterinary composition comprising as active ingredient an aminoacetonitrile compound of the formula I as defined in claims 1 to 6 or an enantiomers thereof and a suitable physiologically acceptable carrier.

8. Veterinary composition according to claim 7 consisting of a solution, emulsion, suspension, feed additive, powder, tablet, bolus, capsule, microencapsule, pour-on, spray- on, spot-on, drench or an injectable formulation.

9. Use of a compound of formula I according to claim 1 in a process for controlling endoparasites on warm-blooded animals.

10. Use of a compound of formula I according to claim 1 in the preparation of a veterinary composition against endoparasites.

1 1 . Method of controlling endoparasites on warm-blooded animals comprising the administration of a pesticidally amount of a compound as defined in claim 1 to the endoparasite.