WO1997036582A1 - Use of substituted aryl imidazoles - Google Patents

Abstract

The present invention relates to the use of aryl imidazoles of formula (I), in which Ar is possibly substituted aryl, W is halogen alkyl, A is hydrogen or CH2R, R is possibly substituted aryl or one or the radicals -OR1, -SR1 or -N(R2)COR3, and Y is halogen, trifluoromethyl, nitro, -S(O)¿nR?6, CN or -CONR4R5 or possibly substituted aryl, where R1 is hydrogen, possibly substituted alkyl, cycloalkyl, alkenyl, alkinyl, aryl or aralkyl, R2 is hydrogen, alkyl, halogen alkyl, cycloalkyl or possibly substituted aryl, R3 is (X)¿mR?7, X is O, S, -N(R8)2-, m is 0 or 1, R?4, R5, R8¿ are mutually independently hydrogen, alkyl or possibly substituted aryl, R6 is alkyl, halogen alkyl or possibly substituted aryl and R7 is alkyl, halogen alkyl or possibly substituted aryl, aralkyl or hetaryl and n is 0, 1 or 2, for combatting parasitic protozoa.

Description

Use of substituted aryl imidazoles

The present invention relates to the use of substituted aryl imidazoles as agents for combating parasitic protozoa and in particular

Coccidia and fish and insect parasites.

Aryl-haloalkylimidazoles and their use as fungicides, insecticides and herbicides have already been disclosed (WO 95/17390, WO 95/04724, EP 283 173, WO 95/33730)

It has been found that aryl imidazoa of the formula (I)

in which

Ar represents optionally substituted aryl,

W represents haloalkyl,

A represents hydrogen or CH ₂ R,

R represents optionally substituted aryl or one of the radicals -OR ¹ , -SR ¹ or -N (R ² ) COR ³ and

Y represents halogen, trifluoromethyl, nitro, -S (O) _n R ⁶ , CN, -CONR ⁴ R ⁵ or optionally substituted aryl,

R ¹ for hydrogen, for each optionally substituted alkyl, cycloalkyl.

Alkenyl, alkynyl. Aryl or aralkyl,

R ^"represents hydrogen, alkyl, haloalkyl, cycloalkyl or optionally substituted aryl, R ^{3 stands} for (X) _m R ⁷ ,

R ⁸ IX stands for O, S or ^N ,

m represents 0 or 1,

R ⁴ , R ⁵ , R ⁸ independently of one another represent hydrogen, alkyl or optionally substituted aryl,

R ^{6 represents} alkyl, haloalkyl or optionally substituted aryl and

R ^{7 represents} alkyl, haloalkyl or optionally substituted aryl, aralkyl or hetaryl and

n represents 0, 1 or 2,

are excellent for fighting parasitic protozoa

The following formulas (la), (Ib) and (lc)

in which A, Ar, W and Y have the meanings given above,

represent preferred substitution patterns.

The aryl imidazoles which can be used according to the invention are known and are generally defined by the formula (I).

Preferred substituents or ranges of the radicals listed in the formulas mentioned above and below are explained below.

Ar preferably represents optionally mono- or polysubstituted by identical or different halogen, nitro, cyano, C _j -C _j2 alkyl, C, -C ₁₂ alkylthio, CpC ^ alkoxy, optionally substituted by, or doubly linked dioxyalkylene by -OCF ₂ Z, -S (O), CF ₂ Z or -CFR ⁹ R ¹⁰ , substituted C ₆ -C _{] 0} aryl

W preferably represents C, -C ₆ -haloalkyl

A preferably represents hydrogen or CH ₂ R

R preferably represents phenyl which is optionally monosubstituted to trisubstituted by halogen, cyano, nitro, C, -C ₆ -alkyl, C _r C ₆ -haloalkyl or C, -C ₆ -alkoxy or one of the radicals -OR ¹ , -SR ¹ , -N (R ² ) COR ³

Y preferably represents halogen, trifluoromethyl, nitro, -S (O) _n R ⁶ , CN,

-CONR ⁴ R ⁵ or for optionally single to triple, identical or different by halogen, cyano, nitro, by optionally substituted double-linked dioxyalkylene or by -OCF ₂ Z,

-S (O) _n CFR ⁹ R ¹⁰ , -CFR ⁹ R ¹⁰ substituted C ₆ -C _{] 0} aryl

R ¹ preferably represents hydrogen, C _r C ₆ alkyl, C _r C ₄ alkoxy-C _r C ₆ alkyl,

C _r C ₆ haloalkyl, C ₃ -C ₆ cycloalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ haloalkenyl, C ₂ -C ₆ alkynyl, C ₂ -C ₆ haloalkynyl or for each up to three times, if necessary, the same or different by halogen,

C, -C ₆ alkyl or C _r C ₆ alkoxy substituted phenyl or benzyl R ² preferably represents hydrogen, C _r C ₆ alkyl, C _r C ₆ haloalkyl, C ₃ -C ₆ cycloalkyl or optionally optionally up to triple by halogen, C _j -C ₆ alkyl or C _r C ₆ - Alkoxy substituted phenyl

R ³ preferably represents (X) _m R ⁷ .

X preferably represents O.

m is preferably 0 or 1.

R ⁴ and R ⁵ independently of one another preferably represent hydrogen, C _r C ₆ alkyl or phenyl which is optionally monosubstituted to trisubstituted identically or differently by halogen or CpC ₈ alkyl

R ⁶ preferably represents C, -C ₆ alkyl, C, -C ₆ haloalkyl or, if appropriate, mono- to trisubstituted or differently substituted by halogen, C ₁ -C ₆ alkyl or C, -C ₆ alkoxy

R ⁷ is preferably C, -C ₆ alkyl, C _r C ₆ haloalkyl, which is optionally monosubstituted to trisubstituted by halogen, C _j ^ -C alkyl, C ^ Cg alkoxy, trifluoromethyl, cyano or nitro-substituted phenyl or benzyl or for pyridyl or pyridylmethyl which is optionally monosubstituted to trisubstituted identically or differently by halogen, C 1 -C ₄ -alkyl or C 1 -C ₆ -alkoxy

R ⁹ and R ¹⁰ independently of one another preferably represent hydrogen or halogen.

Z preferably represents hydrogen, halogen or C, -C ₆ -haloalkyl

1 preferably represents 0, 1 or 2

n is preferably 0, 1 or 2

Ar particularly preferably represents optionally one to three times, identical or different by halogen, nitro, cyano, by optionally Halogen-substituted, double-linked dioxyalkylene with 1 to 4 carbon atoms or up to twice by

-OCF ₂ Z, -S (O), CF ₂ Z or -CFR ⁹ R ¹⁰

substituted phenyl.

W particularly preferably represents C _] -C ₄ -alkyl which is substituted by fluorine or chlorine

A particularly preferably represents hydrogen or CH ₂ R

R particularly preferably represents one of the radicals -OR ¹ , -SR ¹ , -N (R ² ) COR ⁷ or N (R ² ) CO ₂ R ⁷

Y particularly preferably represents halogen, trifluoromethyl, nitro for -S (O) _n R ⁶ ,

CN, CONR ⁴ R ⁵ or for phenyl which is optionally monosubstituted to trisubstituted, identically or differently, by halogen, cyano, nitro or by -OCF ^ Z, -S (O) _n CFR ⁹ R ¹⁰ or -CFR ⁹ R ¹⁰

R particularly preferably represents hydrogen, C 1 -C ₄ -alkyl, C ₃ -C ₆ cycloalkyl, C ₂ -C ₄ alkenyl optionally substituted by one to three fluorine and / or chlorine atoms or by methoxy or ethoxy , C ₂ -C ₄ alkynyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ haloalkynyl or for optionally single to triple, identical or different by F, Cl, Br, C, -C ₄ alkyl or C _j -C ₄ alkoxy substituted phenyl

R ² particularly preferably represents hydrogen, C _r C ₄ alkyl, C _j -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl or optionally single to triple, identical or different, by fluorine, chlorine, bromine, C , -C ₄ alkyl or C, -C ₄ alkoxy substituted phenyl

R ⁴ and R ⁵ independently of one another particularly preferably represent hydrogen, C, -C ₄ alkyl or phenyl which is optionally monosubstituted to trisubstituted by fluorine, chlorine, bromine or C _r C ₄ alkyl R ⁶ particularly preferably represents single to triple, identical or different, methyl-substituted by fluorine, chlorine and / or bromine.

R ⁷ in -N (R ² ) CO ₂ R ^{7 is} particularly preferably C _r C ₄ alkyl.

R ⁷ in -N (R ² ) COR ⁷ particularly preferably represents C ₁ -C ₄ -alkyl which is optionally substituted by halogen, each in each case optionally up to triple, identically or differently, by fluorine, chlorine, bromine, C ₁ -C ₄ - Alkyl or C ₁ -C ₄ alkoxy substituted phenyl or pyridyl.

R ⁹ and R ¹⁰ independently of one another particularly preferably represent hydrogen, fluorine, chlorine or bromine.

Z particularly preferably represents hydrogen, fluorine, chlorine or monosubstituted or polysubstituted by fluorine and / or _chlorine-C] -C ₄ alkyl

1 particularly preferably represents 0 or 1

n particularly preferably represents 0, 1 or 2.

Ar very particularly preferably represents optionally one to three times, identical or different by fluorine, chlorine, bromine, nitro, cyano, by optionally linked by one to four fluorine and / or chlorine atoms, double-linked dioxyalkylene having one or two carbon atoms or up to two times by

-OCF ₂ Z, -S (O), CF ₂ Z or -CFR ⁹ R ¹⁰

substituted phenyl

W very particularly preferably represents CF ₃ or C ₂ F ₅

A very particularly preferably represents hydrogen or CH ₂ R

R very particularly preferably represents a radical of the formula -OR ¹ , -SR ¹ ,

-N (R ² ) CO ₂ R ⁷ or -NHCOR ⁷ Y very particularly preferably represents chlorine, bromine, trifluoromethyl, nitro or optionally single to triple, identical or different, by fluorine, chlorine, bromine, cyano, nitro or by -OCF ₂ Z, -S (O) _n CFR ⁹ R ¹⁰ or -CFR ⁹ R ¹⁰ substituted phenyl.

R ¹ very particularly preferably represents methyl, ethyl, n- or i-propyl, n-, see-, i- or t-butyl optionally substituted by one to three fluorine and / or chlorine atoms or by methoxy, cyclopropyl, cyclopentyl , for 2-propenyl, 2-butenyl, 4-chloro-2-butenyl, 2-propynyl, 4-chloro-2-butynyl or for phenyl optionally substituted by fluorine, chlorine, bromine, methoxy or methyl.

R ² very particularly preferably represents hydrogen, optionally substituted by one to three fluorine and / or chlorine atoms, methyl, ethyl, n- or i-propyl, n-, see-, I- or t-butyl, cyclopropyl, cyclopentyl or for phenyl which is optionally monosubstituted to trisubstituted identically or differently by fluorine, chlorine, bromine, methyl or methoxy

R ⁷ in -N (R ² ) CO ₂ R ⁷ very particularly preferably represents methyl, ethyl, n- or i-propyl, n-, see-, i- or t-butyl

R 'in -NHCOR' very particularly preferably represents methyl, ethyl, n- or i-propyl, n-, see-, 1- or t-butyl optionally substituted by one to three fluorine and / or chlorine atoms or optionally optionally simple up to three times the same or different by fluorine, chlorine, bromine, methyl or

Methoxy substituted phenyl

R ⁹ and R ¹⁰ independently of one another very particularly preferably represent hydrogen, fluorine or chlorine

Z very particularly preferably represents hydrogen, fluorine, chlorine, difluoromethyl, trifluoromethyl, chlorofluoromethyl or the rest of the formula -CHFCF ₃

1 very particularly preferably represents 0

n very particularly preferably represents 0 or] The general definitions or explanations given above, or those listed in preferred areas, can be combined with one another, that is to say also between the respective area and preferred areas.

Preference is given to using the compounds of the general formula (I) in which there is a combination of the meanings listed above as preferred (preferred).

The compounds of the general formula (I) in which a combination of these meanings listed above as very particularly preferred are used with very particular preference.

The following arylimidazoles of the general formula (Ia) may be mentioned in particular:

The following arylimidazoles of the general formula (Ib) may be mentioned in detail:

The following arylimidazoles of the general formula (lc) may be mentioned in detail

The following may be mentioned as particularly preferred compounds from the series of arylimidazoles of the formula (Ia):

The following may be mentioned as particularly preferred compounds from the series of the arylimidazoles of the formula (Ib):

The following may be mentioned as particularly preferred compounds from the series of arylimidazoles of the formula (lc):

The compounds which can be used according to the invention can be used excellently in mixtures with synthetic coccidiosis agents or polyether antibiotics. Compared to the effect of the individual components, these mixtures sometimes show considerable increases in effectiveness (synergism). They can also be used advantageously in control programs alternating with synthetic coccidiosis or polyether antibiotics.

Maduramycin, lasalocid, monensin, narasin, salinomycin, semduramycin may be mentioned as polyether antibiotics. The following may be mentioned as synthetic coccidiosis: l (- (4-Amino-2-n-propyl-5-pyrimidinylmethyl) -2-picoline amprolium chloride I (- (4-Amino-2-n-propyl-5-pyrimidinylmethyl) -2-picolinium amprolium + chloride + sulfaquinoxaline sulfaquinoxaline 1 (- (4-amino-2-n-propyl-5-pyrimidinylmethyl) -2-picolinium-amprolium + chloride + sulfaquinoxaline + ethopabate sulfaquinoxaline + ethopabate

4,4-dinitrocarbanilide + 2-hydroxy-4,6-dimethylpyrimidine nicarbazine

3,5-dichloro-2,6-dimethyl-4-pyridinol clopidol

3,5-dichloro-2,6-dimethyl-4-pyridinol + methyl-7-benzyloxy-clopidol + 6-butyl-l, 4-dihydro-4-oxylquinoline-3-carboxylate methyl benzoquate

Ethyl 6-n-decyloxy-7-ethoxy-4-hydroxyquinoline-3-carboxylate decoquinate

9- (2-Chloro-6-fluorophenylmethyl) -9H-purine-6-amine arprinocid

(±) -2,6-dichloro-alpha- (4-chlorophenyl) -4- (4,5-dihydro-3,5-benzeneacetone-dioxo- 1, 2,4-triazin-2 (3H) -yl) -benzeneacetonitrile tril, diclazuril 1 - [3-methyl-4- (4'-trifluoromethylthiophenoxy) phenyl] -3- toltrazuril methyl-l, 3,5-trιazin-2,4,6 (lH, 3H, 5H) - trion

4,4-dinitrocarbanilide + 2-hydroxy-4,6-dimethylpyrimidine robenidine [= nicarbazine]

7-bromo-6-chloro-febrifugin halofuginone 3,5-dinitro-o-toluamide zoalen.

The active ingredients are suitable for combating parasitic protozoa which are found in animal husbandry and animal breeding in useful, breeding, zoo, laboratory, experimental and hobby animals, with favorable warm-blooded toxicity. They are effective against all or individual stages of development of the pests and against resistant and normally sensitive strains. By fighting parasitic

Protozoa should reduce illness, deaths and reduced performance (eg in the production of meat, milk, wool, hides, eggs, honey, etc.) so that the use of the active ingredients enables more economical and simple animal husbandry. Parasitic protozoa include.

Mastigophora (Flagellata) such as Trypanosomatidae e.g. Trypanosoma b. brucei, T b. gambiense, T b rhodesiense, T. congolense, T. cruzi, T. evansi, T. equinum, T. lewisi, T percae, T. simiae, T vivax, Leishmania brasiliensis, L donovani, L tropica, such as Trichomonadidae such as Trichomonas vaginalis, Tritrichomonas foetus, such as, for example, Diplomonadida Giardia lamblia, G canis.

Sarcomastigophora (Rhizopoda) such as Entamoebidae e.g. Entamoeba histolytica, Hartmanellidae e.g. Acanthamoeba sp, Hartmanella sp

Apicomplexa (Sporozoa) such as Eimeridae e.g. Eimeria acervulina, E adenoides, E alabahmensis, E anatis, E anseris, E arloingi, E ashata, E auburnensis, E bovis,

E brunetti, E canis, E chinchillae, E clupearum, E columbae, E contorta, E crandalis, E debliecki, E dispersa, E ellipsoidales, E falciformis, E faurei, E fiavescens, E gallopavonis, E hagani, E intestinalis, E iroquoina , E irresidua, E labbeana, E leucarti, E magna, E maxima, E media, E meleagridis, E meleagrimitis, E mitis, E necatπx, E ninakohlyakimovae, E ovis, E parva, E pavonis, E perforans, E phasani, E piriformis, E praecox, E residua, E scabra, E spec, E stiedai, E suis, E tenella, E truncata, E truttae, E zuernπ, Globidium spec, Isospora belli, I canis, I felis, I ohioensis, I rivolta, I spec, I suis, Cystisospora spec, Cryptosporidium spec like Toxoplasmadidae e.g. Toxoplasma gondii, like Sarcocystidae e.g. B Sarcocystis bovicams, S bovihominis, S ovicanis,

S ovifelis, S spec, S suihominis such as Leucozoidae z B Leucozytozoon simondi, such as Plasmodiidae z B Plasmodium berghei, P falciparum, P malaπae, P ovale, P vivax, P spec, such as Piroplasmea z B Babesia argentina. B bovis, B canis, B spec, Theileπa parva, Theileria spec, such as Adeleina z B Hepatozoon canis, H spec

Furthermore Myxospora and Microspora eg Glugea spec Nosema spec

Furthermore Pneumocystis carinii, as well as Ciliophora (Ciliata) such as Balantidium coli, Ichthiophthiπus spec, Trichodina spec, Epistyhs spec

The compounds according to the invention are also active against protozoa which occur as parasites in insects. Parasites of the strain may be mentioned as such

Microsporida, in particular of the genus Nosema. Nosema apis is particularly mentioned in the honey bee The livestock and breeding animals include mammals such as cattle, horses, sheep, pigs, goats, camels, water buffalos, donkeys, rabbits, fallow deer, reindeer, fur animals such as mink, chinchilla, raccoon, birds such as chickens, geese, turkeys, Ducks, pigeons, bird species for home and zoo keeping. It also includes farm and ornamental fish.

Laboratory and experimental animals include mice, rats, guinea pigs, golden hamsters, dogs and cats

The pets include dogs and cats.

The fish include farmed, farmed, aquarium and ornamental fish of all ages, which live in fresh and salt water

Carp, eel, trout, white fish, salmon, bream, roach, rudd, dobel, sole, plaice, halibut, Japanese yellowtail (Seriola quinqueradiata), Japanese eel (Anguilla japonica), red seabream (Pagurus major), seabass (Dicentrarchus labrax ), Gray mullet (Mugilus cephalus), Pompano, Gilthread seabream (Sparus auratus), Tilapia spp, Chichlid species such as Plagioscion, Channel catfish

The compositions according to the invention are particularly suitable for the treatment of fish brood, for example carp of 2-4 cm in body length. The compositions are also very suitable for eel fattening

The application can be prophylactic as well as therapeutic

The active ingredients are used directly or in the form of suitable preparations enterally, parenterally, dermally, nasally

The enteral application of the active ingredients takes place, for example, orally in the form of powder, suppositories, tablets, capsules, pastes, drinkers, granules, drenches, boluses, medicated feed or drinking water. The dermal application takes place, for example, in the form of diving (dipping), spraying (spraying) , Bathing, washing, pouring

(pour-on and spot-on) and powdering Parenteral use is, for example, in the form of injection (intramuscular, subcutaneous, intravenous, intrapeπtoneal) or by implants

Suitable preparations are Solutions such as injection solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, infusion formulations, gels;

Emulsions and suspensions for oral or dermal use and for injection; Semi-solid preparations;

Formulations in which the active ingredient is processed in an ointment base or in an oil in water or water in an oil emulsion base,

Solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, boluses, capsules, aerosols and inhalants, molded articles containing active ingredients

Injection solutions are administered intravenously, intramuscularly and subcutaneously

Injection solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly adding additives such as solution mediators, acids, bases, buffer salts, antioxidants, preservatives. The solutions are sterile filtered and filled

Physiologically contractual solvents such as

Water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, hydrocarbons, propylene glycol, polyethylene glycols, N-methyl-pyrrolidone, and mixtures thereof

The active ingredients can optionally also be dissolved in physiologically acceptable vegetable or synthetic oils which are suitable for injection

Solvents which may be mentioned are solvents which require the active ingredient to be dissolved in the main solvent or prevent it from precipitating out. Examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters

Preservatives are benzyl alcohol, trichlorobutanol, p-hydroxybenzoate, n-butanol Oral solutions are used directly. After prior dilution to the application concentration, concentrates are administered orally. Oral solutions and concentrates are produced as described above for the injection solutions, and sterile work can be dispensed with

Solutions for use on the skin are dripped on, spread on, rubbed in, sprayed on, sprayed on or applied by dipping (dipping), bathing or washing. These solutions are prepared as described above for the injection solutions

It can be advantageous to add thickeners in the preparation. Thickeners are inorganic thickeners such as bentonites, colloidal

Silicic acid, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and metacrylates

Gels are applied or spread onto the skin or placed in body cavities. Gels are produced by adding solutions, which have been prepared as described for the injection solutions, with so much thickening agent that a clear mass with ointment-like consistency is produced thickeners, the thickeners specified above are used

Pour-on formulations are poured or sprayed onto limited areas of the skin, the active ingredient either penetrating the skin and acting systemically or being distributed over the surface of the body

Pour-on formulations are produced by dissolving, suspending or emulsifying the active ingredient in suitable skin-compatible solvents or solvent mixtures. If necessary, other auxiliaries such as dyes, absorption-promoting substances, antioxidants, light stabilizers and adhesives are added

Water, alkanols, glycols, polyethylene glycols,

Polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzylbenzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol monobutyl ether, ketones such as acetone, methyl ethyl ketonic alcohols, aromatic and / or, aromatic and / or, aromatic or or synthetic oils, DMF,

Dimethyiacetamide, N-methylpyrrohdon, 2-dimethyl-4-oxy-methylene-1, 3-dimoxolane Dyes are all dyes approved for use on animals, which can be dissolved or suspended.

Absorbing substances are e.g. DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol

Light stabilizers are, for example, substances from the class of benzophenones or novanti sol acid

Adhesives are, for example, cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin

Emulsions can be used orally, dermally or as injections

Emulsions are either of the water in oil type or of the oil in water type

They are produced by dissolving the active ingredient either in the hydrophobic or in the hydrophilic phase and then using the solvent with the aid of suitable emulsifiers and, if appropriate, other auxiliaries such as dyes, absorption-promoting substances, preservatives, antioxidants, light stabilizers, viscosity-increasing substances homogenized the other phase

Paraffinols, silicone oils, natural vegetable oils such as sesamol, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid bigylceride, triglyceride mixture with vegetable fatty acids are mentioned as the hydrophobic phase (ole)

Chain length C ₈ _ ₁₂ or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids which may also contain hydroxyl groups, mono- and diglycerides of C ₈ / C _{] 0} fatty acids

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate. Lauπnsaurehexylester, dipropylene glycol pelargonate, esters of a branched fatty acid medium chain length with saturated fatty alcohols of chain length C ₁₆ -C ₁₈ , isopropyl myristate, isopropyl palmitate, caprylic / capric acid ester of saturated fatty alcohols of the chain long C _n -C ₁₈ . isopropyl stearate, oleic acid olylester, oleic acid decyl ester, ethyl oleate, Lactic acid ethyl ester, waxy fatty acid esters such as dibutyl phthalate, adipic acid diisopropyl ester, the latter related ester mixtures, inter alia fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetyl stearyl alcohol, oleyl alcohol.

Fatty acids such as Oleic acid and its mixtures.

The following can be mentioned as the hydrophilic phase:

Water, alcohols such as e.g. Propylene glycol, glycerin, sorbitol and their mixtures.

The following may be mentioned as emulsifiers: nonionic surfactants, e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether;

ampholytic surfactants such as di-Na-N-lauryl-β-iminodipropionate or lecithin;

anionic surfactants, such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt;

cationic surfactants such as cetyltrimethylammonium chloride.

The following may be mentioned as further auxiliaries: substances which increase the viscosity and stabilize the emulsion, such as carboxymethyl cellulose, methyl cellulose and others

Cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal silica or mixtures of the substances listed.

Suspensions can be used orally, dermally or as an injection. They are produced by suspending the active ingredient in a carrier liquid, optionally with the addition of other auxiliaries such as wetting agents, dyes, absorption-promoting substances, preservatives, antioxidants, light stabilizers.

All homogeneous solvents and solvent mixtures are mentioned as carrier liquids. The surfactants specified above may be mentioned as wetting agents (dispersants).

Further additives mentioned are those mentioned above.

Semi-solid preparations can be administered orally or dermally. They differ from the suspensions and emulsions described above only in their higher viscosity.

To prepare solid preparations, the active ingredient is mixed with suitable excipients, if appropriate with the addition of auxiliaries, and brought into the desired form.

All physiologically compatible solid inert substances may be mentioned as carriers.

All of these serve inorganic and organic substances. Inorganic substances are e.g. Table salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays, precipitated or colloidal silicon dioxide, phosphates.

Organic substances are e.g. Sugar, cellulose, food and feed such as

Milk powder, animal meal, cereal flour and meal, starches.

Excipients are preservatives, antioxidants, dyes, which have already been listed above.

Other suitable auxiliaries are lubricants and lubricants such as Magnesium stearate, stearic acid, talc, bentonite, decay-promoting substances such as starch or cross-linked polyvinylpyrrolidone, binders such as e.g. Starch, gelatin or linear polyvinylpyrrolidone and dry binders such as microcrystalline cellulose.

The active substances can also be present in the preparations as a mixture with synergists or with other active substances.

Ready-to-use preparations contain the active ingredient in concentrations of 10 ppm to 20 percent by weight, preferably 0.1 to 10 percent by weight. Preparations which are diluted before use contain the active ingredient in concentrations of 0.5-90 percent by weight, preferably from 1 to 50 percent by weight.

In general, it has proven to be advantageous to administer amounts of about 0.5 to about 50 mg, preferably 1 to 20 mg, of active ingredient per kg of body weight per day in order to achieve effective results.

The active ingredients can also be administered together with the animal's feed or drinking water.

Feed and food contain 0.01 to 100 ppm, preferably 0.5 to 50 ppm of the active ingredient in combination with a suitable edible material

Such feed and food can be used for medicinal purposes as well as for prophylactic purposes.

Such a feed or foodstuff is produced by mixing a concentrate or a premix containing 0.5 to 30%, preferably 1 to 20% by weight of an active ingredient in admixture with an edible organic or inorganic carrier with conventional feedstuffs are, for example, corn flour or corn and soybean flour or mineral salts, which preferably contain a small amount of an edible dust-preventing oil, for example corn oil or soybean oil. The premix obtained in this way can then be added to the complete feed before it is fed to the animals.

One example is the use in coccidiosis.

For the healing and prophylaxis of, for example, coccidiosis in poultry, in particular in chickens, ducks, geese and turkeys, 0.1 to 100 ppm, preferably 0.5 to 100 ppm, of an active ingredient with a suitable edible material, for example a nutritious feed, are used , mixed If desired, these can

Amounts are increased, especially if the active ingredient is well tolerated by the recipient. Accordingly, the administration can take place via the drinking water

For the treatment of individual animals, for example in the case of the treatment of coccidiosis in mammals or toxoplasmosis, amounts of active substance are preferred from 0.5 to 100 mg / kg body weight administered daily in order to achieve the desired results. Nevertheless, it may be necessary at times to deviate from the amounts mentioned, in particular depending on the body weight of the test animal or the type of administration method, but also because the animal species and its individual reaction to the active ingredient or the type of formulation and the time or the interval at which it is administered. In certain cases it may be sufficient to make do with less than the minimum amount mentioned above, while in other cases the the upper limit mentioned must be exceeded. When administering large quantities, it may be advisable to divide them into several individual forms during the day

The parasites in fish include from the sub-realm of the protozoan species of the strain of the Cihata, e.g. Ichthyophthiπus multifilπs, Chilodonella cypπni, Tπchodina spp, Glossatella spp, Epistyhs spp of the strain of Myxospoπdia, e.g. Myxosxiumiumbrppus, Myxidomolebium sppya, Myxidomolegu sppya, Myxidoma sppya spp,

Hoferellus spp, the class of Mikrospoπdia eg Glugea spp, Thelohania spp, Pleistophora spp, from the strain of the Plathelminths Trematodes, Monogenea z B Dactylogyrus spp, Gyrodactylus spp, Pseudodactylogyrus spp, Diplozoon Cpp from denyllidea (denyll groups, denyl groups, Cestidea der Cyllodenea e.g. Caryophyllaeus laticeps), Pseudophylhdea (e.g. Diphyllobothπum spp), Tetraphyllidea (e.g.

Phyllobothπum spp) and Protocephahda (e.g. species of the genus Proteocephalus) and various parasitic crustaceans from the trunk of the Arthropoda, in particular from the subclasses of the Branchiura (fish louse) and Copepoda (oar crabs) as well as the orders of the Isopoda (woodlice) and Amphipoda (woodlice Amphipods)

The fish are treated either orally, eg via the feed, or by short-term treatment, "medical bath", in which the fish are placed and in which they are kept for a time (minutes to several hours), for example when moving from one breeding tank to another

But it can also be a temporary or permanent treatment of the

Habitat of the fish (e.g. entire pond systems, aquariums, tanks or basins) in which the fish are kept The active ingredient is administered in preparations which are adapted to the applications

The concentration of the active ingredient in the preparations is 1 ppm to 10% by weight

Preferred preparations for short-term treatment when used as

"Medical bath" eg in the treatment when the fish are moved or for the treatment of the habitat (pond treatment) of the fish are solutions of the active ingredient in one or more polar solvents which react alkaline when diluted with water

To prepare these solutions, the active ingredient is dissolved in a polar, water-soluble solvent which either reacts in an alkaline manner or to which an alkaline water-soluble substance is added. The latter is also advantageously dissolved in the solvent, but can also be suspended in the solvent and only in the water loose After adding the active ingredient solution, the water should have a pH of 7-10, but preferably a pH of 8-10

The concentration of the active ingredient can be in the range from 0.5-50%, but preferably in a range from 1-25%

All water-soluble solvents in which the active ingredient is soluble in sufficient concentration and which are physiologically harmless are suitable as solvents.

These are ethyl alcohol, isopropyl alcohol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycols, poly (oxoethylene) poly (oxypropylene) polymers, basic alcohols such as mono-, di- and Tn ethanol amine, ketones such as acetone or methyl ethyl ketone, esters such as Lactic acid ethyl ester also N-methylpyrrolidone,

Dimethylacetamide, dimethylformamide, also dispersants and emulsifiers such as polyoxyethylated castor oil, polyethylene glycol sorbitan monooleate, polyethylene glycol stearate, or polyethylene glycol ether, polyethylene glycol alkyl amines

As bases for adjusting the alkaline pH, organic bases such as basic amino acids such as L- or D, L-Argιnιn, L- or D, L-lysine may be mentioned, Methylglucosamine, glucosamine, 2-amino-2-hydroxymethylpropanediol- (1,3) also like N, N, N ', N'-tetrakis (2-hydroxypropyl) -ethylenediamine or polyether-tetrol based on ethylenediamine (MW 480- 420), inorganic bases, such as ammonia or sodium carbonate - optionally with the addition of water

The preparations can also contain 0.1 to 20% by weight, preferably 0.1-10% by weight, of other formulation auxiliaries, such as antioxidants, surfactants, suspension stabilizers and thickeners, such as, for example, methyl cellulose, alginates, polysaccharides, galactomannans and colloidal silica . The addition of color, aroma and builders for animal nutrition is also possible. Acids, which together with the base provided form a buffer system or the pH of the

Reduce the solution should be mentioned here

The concentration of the active ingredient depends on the type and duration of the treatment, as well as the age and condition of the treated fish. For short-term treatment, for example, it is 2-50 mg active ingredient per liter of water, preferably 5-10 mg per liter, for a treatment duration of 3- 4 hours When treating young carp, for example, a concentration of 5-10 mg / 1 and a treatment time of approx. 1-4 hours are used

Eels are treated with concentrations of approx. 5 mg / 1 for approx. 4 hours

In the case of longer treatment times or long-term treatment, the concentration can be chosen correspondingly lower

For pond treatments, 0.1-5 mg of active ingredient per liter of water can be used

Preparations for use as feed additives are composed, for example, as follows a) Active ingredient of the 10 parts by weight of formula I soybean protein 49-90 parts by weight

b) Active ingredient of 0.5-10 parts by weight of formula I benzyl alcohol 0.08-1.4 parts by weight of hydroxypropyl- 0-3.5 parts by weight of methylcellulose water remainder ad 100

Preparations for use in "medical baths" and for pond treatment are composed and produced, for example, as follows

c) 2.5 g of active ingredient of the formula (I) are dissolved in 100 ml of triethanolamine with heating

d) 2.5 g of active ingredient of formula (I) 12.5 g of lactic acid are heated in 100 ml of triethanolamine and

Ruhren solved

e) 10.0 g of active ingredient of the formula (I) is dissolved in 100 ml of monoethanolamine

0 active ingredient of the formula I 5.0 g

Propylene glycol 50.0 g

Sodium carbonate 5.0 g

Water to 100 ml

g) Active ingredient of the formula I 5.0 g

Monoethanolamine 10 g

N-Methy Ipy rrol i don ad 100 m

h) active ingredient of the formula I 2.5 g

Sodium carbonate 5.0 g

Polyethylene glycol 200 ad 100 ml The active ingredient is dissolved in polyethylene glycol under heating and sodium carbonate is suspended therein

An active ingredient-containing feed is usually prepared with the compounds according to the invention in such a way that about 0.1 to 5000 ppm, preferably 0.1 to 100 ppm, of active ingredient with a nutritionally balanced animal feed, for example with the chicken feed described in the following example, is thoroughly mixed

If a concentrate or a premix is to be prepared, which is ultimately to be diluted in the feed to the above-mentioned values, about 1 to 30%, preferably about 10 to 20% by weight of active ingredient are generally used with an edible organic or inorganic Carrier, e.g. corn and soy flour or mineral salts containing a small amount of an edible dedusting oil, e.g. corn oil or soybean oil, mixed. The premix obtained in this way can then be added to the whole poultry feed before administration

The following composition can be considered as examples of the use of the substances according to the invention in poultry feed

52.00% feed grain, 40% corn, 12% wheat

17.00% soybean meal extr

5.00% corn gluten feed

5.00% wheat feed flour

3.00% fish meal

3.00% mineral fabric mix

3.00% alfalfa grass flour

2.50% vitamin premix

2.00% wheat germ, crushed

2.00% soybean oil

2.00% meat bone meal

1.50% whey powder

1.00% molasses

1.00% brewer's yeast, bound to beer spent grains

100.00% Such feed contains 18% crude protein, 5% crude fiber, 1% Ca, 0.7% P as well as 1200 iE vitamin A, 1200 iE vitamin D ₃ , 10 mg vitamin E, 20 mg zinc bacitracin per kg.

The effectiveness of the compounds according to the invention is shown by the following example without any limitation with regard to the chemical width of their

To give applicability.

Example A

Cage trial coccidiosis / chick

Cocci male chickens, 8 to 12 days old, raised free of service (eg LSL Brinkschulte / Senden) received the present invention from 3 days before (day -3) the infection (= a i.) To 8 (9) days after the infection (= pi) Compounds (test substances) in the concentration given in ppm with the feed. 3 animals are kept in each cage. One to several such groups are used per dosage. The infection occurs by means of a pharyngeal tube directly into the goiter with about 100,000 sporulated oocysts from Eimeria acervulina and with about 5-80,000 sporulated oocysts from E. maxima and E. tenella. These are highly virulent strains. The exact dose of infection is set so that one of three experimentally infected untreated chicks dies as a result of infection. The following criteria are taken into account for the assessment of the effectiveness: weight gain from the start of the trial to the end of the trial, infection-related death rate, macroscopic assessment of the

Faeces with regard to diarrhea and blood excretion on days 5 and 7 p.i., macroscopic assessment of the intestinal mucosa, in particular the appendix and the oocyst excretion as well as the proportion (in%) of the oocysts sporulating within 24 hours. The number of oocysts in the faeces was determined using the McMaster counting chamber (see Engelbrecht and co-workers

"Parasitological working methods in medicine and veterinary medicine, Akademie-Verlag, Berlin (1965)). The individual findings are related to the untreated infected and the untreated uninfected control groups and an overall evaluation is calculated (cf. A. Haberkorn (1986) pp. 263-270 in Research in Avian Coccidiosis ed. LR McDougald, L P. Joyner, PL Long

Proceedings of the Georgia Coccidiosis Conference Nov. 1 8-20. 1995 Athens / Georgia USA). The effectiveness is rated as follows: 2 = fully effective; 1 = partially effective; 0 = ineffective. Table 1

Efficacy of exemplary compounds against coccidia (E acervulina, E. maxima, E tenella) in the chick

= fully effective, 1 = partially effective, 0 = ineffective, + = dead inf toxicity

Claims

Claims

1. Use of aryl imidazoles of the formula (I)

in which

Ar represents optionally substituted aryl,

W represents haloalkyl,

A represents hydrogen or CH ₂ R,

R represents optionally substituted aryl or one of the radicals -OR ¹ , -SR ¹ or -N (R ² ) COR ³ and

Y for halogen, trifluoromethyl, nitro, -S (O) _n R ⁶ for CN or

-CONR ⁴ R or represents optionally substituted aryl,

R represents hydrogen, for optionally substituted alkyl,

Cycloalkyl, alkenyl, alkynyl, aryl or aralkyl,

R represents hydrogen, alkyl, haloalkyl, cycloalkyl or optionally substituted aryl,

R ^{3 stands} for (X) _m R ⁷ ,

R ⁸

I.

X stands for O, S, ~ ^N ~,

m represents 0 or 1, R ⁴ , R ⁵ , R ⁸ independently of one another represent hydrogen, alkyl or optionally substituted aryl,

R ^{6 represents} alkyl, haloalkyl or optionally substituted aryl and

R ^{7 represents} alkyl, haloalkyl or optionally substituted aryl, aralkyl or hetaryl and

n represents 0, 1 or 2,

for the production of agents for combating parasitic protozoa in veterinary medicine

Use according to claim 1, characterized in that aryl imidazoles of the formulas (la), (Ib) and (lc)

in which

A, Ar, W and Y have the meanings mentioned in claim 1,

are used as active ingredients 3. Use of aryl imidazoles as a means of combating parasitic protozoa

4. Agent for combating parasitic protozoa, characterized by a content of at least one aryl-imidazole of the formula (I) according to claim 1

5 A method of combating parasitic protozoa, characterized gekenn¬ characterized in that aryl imidazoles of formula (I) according to claim 1 are allowed to act on these and / or their habitat

6 A process for the preparation of agents against parasitic protozoa, characterized in that aryl imidazoles of the formula (I) according to Claim 1 are mixed with extenders and / or surface-active agents