Indian Patents. 224612:1-ARYLPYRAZOLE COMPOUNDS AND COMPOSITION FOR THE CONTROL OF ARTHROPODS

Title of Invention	1-ARYLPYRAZOLE COMPOUNDS AND COMPOSITION FOR THE CONTROL OF ARTHROPODS
Abstract	Novel 1-arylpyrazole compounds and composition are described which are useful for controlling parasites in on an animal

Full Text	Control of Arthropods in Animals Tre present invention relates to a method of control of parasites in animals, compositions comprising a compound effective for the sale control and compounds effective against parasites. !t is generally a goal of agronomists and veterinarians to possess sufficient means to con™i pests, particularly arthropods, when they attempt to invade or attack mammais, particularly domestic animals and/ or livestock. A c;assical method of controlling such pests has been the use of topical and/or systemic pesticides on or in the domestic animal which is being attacked. Generally effective treatments include the oral administration of insect growth regulators, such as lufenuron, or antiheiminth compounds such as an ivermectin or an avermectin, or the topical application of the insecticide fipronil. It is advantageous to apply pesticides tc animals in oral form so as tc prevent the possible contamination of humans or the surrounding environment. !t is an object of the present invention to provide new pesticides which may be used in domestic animals. Another object of the invention is to provide safer pesticides for domestic animals. Another object of the invention Is to provide new pesticioes for domestic animais that .•ray be used in lower doses than existing pesticides. These objects are met in whole or in part by the present invention. US 5,079,370, EP-A 0,846,686, WO 98/24769 and WO 97/23126 disclose the use of sr/ipyrazoles as parasiticidai agents. However, these references are completely silent on the problem that anti parasitical agents cften elicit emesis in the animal to be protected or cured from the parasites. The cresert invention crevices a method of ccntrcilinc sarasliss in or en an animai com^nsing administering, preferably orally, tc the animal a oarasiticidaily effective. substantially non-emetic amount of a l-aryipyrazcie of formula (!}: wherein: R20, is cyano, C(0)aikyl, C(S)NH2, C(NH)OR203, C(NH)SR2C3, alkyl, C(=NOH)NH2, C(=NNH2)NH2, C(0)NH2, C(O)NHR205, C(O)NR205R2C6l haioalkyl or heterocyciyl from the group: optionally substituted by R203; R202 is S(O)hR203, C2-C6 aikenyl, C2-C6 haloalkenyi. cycicalkyi, halocycloalkyi, cycloalkyl-alky! , C2-C5 alkynylT nitro or imidazol-2-yl optionally substituted by alkyl, alkoxy, haioalkyl, halogen, cyano and/or nitro; R2C3 is aikyl or haioalkyl; R2C4 is -OH, RajsO-, HC(0)O, R205C(O)O-, R20£OC(O)O-, NH2C(0)0-, R2C5NHC(0)0-I RzosRsceNCCOJO-, R2C5S(0)RC(0)0-, R206SO2O-, aryl-SO:0-, (C4-C7)-oxacycioalkyloxy, R^R-eN-aNR^J-O-, RM5R206N-C(NH)-O- , R^NH-CiNR-^rC-. R^NH-CfNHVO-. R205N=CH-O-. R2«N=C(R206)-0-f R205NH-C(S)-O-( R2C5R:C£N-C(S)-C- ; R:c5 is alkyl, haioalkyl, cycloalkyi, halocycloalkyi, aikoxyaikyi, haicaikoxyaikyl, adarnantyl, aminoalkyl, alkylaminoalkyl, dialkyiaminoaikyl, haloalkylaminoalkyi, di(haloalkyl)aminoalkyl, aryl optionally substituted, hetaryl optionally substituted, arylaikyl optionally substituted, hetarylalkyi optionally substituted, C2-Cfi alkenyl, C2- C5 alkinyl; R:c6 is aikyi, haicalkyl, cycioalkyi, halocycioaikyl, aikoxyaikyl, haioaikcxyalkyi, aryl optionally substituted, hetaryl optionally substituted, arylaikyl optionally substituted, hetarylalkyi optionally substituted; or R2C5 ar.c R206 may fcrm together with the nitrogen to which they are attached a 3 to 7 membered ring which additionally may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur; X- is selected from nitrogen and C-R212; R:-,f R2,2 are independently selected from halogen, hydrogen, CN, C,-C3 alkyl and NO:; R2-3 is selected from halogen, haloalkyl, haloalkoxy, -S(0)kCF3, and -SF5 or forms a ring with R2«4; R2.4 is hydrogen or may constitute together with R213 a group of OCF20, CF2OCF2, CF.OCF-0 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring; and h. k and r. are independently selected from 0, 1, and 2; am* vciDMidM;jy aooe^uauic SCJUO uicreoi. By the term "veterinarily acceptable salts" is meant salts the anions of which are known and accepted in the art for the formation of salts for veterinary use. Suitable acic addition salts, e.g. formed by compounds of formula (i) containing a basic nitrogen atom, e.g. an amino group, include salts with inorganic acids, for example hydrochlorides, sulphates, phosphates and nitrates and salts with organic acids for exsmcie acetic aciu. When R-. is OH the cvrazoie structure can also be exhibited bv its tautomeric forr': as cvrazcicn structure. Uniess otherwise specified, alkyl and alkoxy groups are straight chain or branched and are generally lower alkyl and alkoxy groups, that is having from one to six carbon atoms, preferably from one to four carbon atoms. Generally, the haicalkyl, haloalkoxy and haioaikylamino groups have from one to four carbon atoms. Halogen means F, CI, Br, and I, preferably F and CI. The haloaikyl and haloalkoxy and haioaikylamino groups can bear one or more halogen atoms; preferred groups of this type include -CF3 and -OCF3. Cycioaikyl groups generally have from 3 to 6 carbon atoms, preferably from 3 to 5 carbon atoms and may be substituted by one or more halogen atoms. Preferably in compounds of formula (I), alkyl groups are generally substituted by from one to five halogen atoms, preferably from one to three halogen atoms. Chlorine and fluorine atoms are preferred. In compounds of formula (I) the following examples of radicals are provided: An example of cycioalkylalkyi is cyclopropylmethyl; an example of cycioalkoxy is cyclopropyloxy;and an example of alkoxyalkyl is CH3OCH2~. Generally, in diaikylamino ordi(haloalkyl)amino radicals, the alkyl and haloaikyl groups on nitrogen may be chosen independently of one another. Generally, the term "aryl" means a carbocyclic aromatic radical having preferably 6 to 14, in particular 6 to 12, carbon atoms, for example phenyl, naphthyl or biphenyiyl, preferably phenyl; the term "heterocyclyi" preferably a hetaryl or heteroaliphatic ring system, "hetaryl" preferably being understood as meaning an aryl radical in which at least one CH group is replaced by N and/or at least two adjacent CH groups are replaced by S, NH or O, for example a radical of thiophene, furan, pyrrole, thiazole, oxazole, imidazole, isothiazole, isoxazoie, pyrazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,3,4- triazole, 1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,3,4- tetrazole, benzo[b]thicphene, benzo[b]furan, indole, benzo[c]thiophene, benzo[c]furan, isoindole, benzoxazole, benzcthiazole, benzimidazole, benzisoxazcie, benziscthiazole, benzcpyrazcie, benzothiatiiazole, benzotriazole, dibenzofuran, dibenzcthicphene, carbazoie, pyridine, pyrazine, pyrimidine, pyridazine, 1,3,5-triazine, 1,2,4-triazine, 1,2,4,5-triazine, quinoline, isoquinoiine, quinoxaline, quinazoline, cinnoline, 1,8-naphthyridine, 1,5-naphthyridine, 1,6-naphthyridine, 1,7-naphthyridine, phthalazine, pyridopyrimidine, purine, pteridine or4H-quinolizine; and the term "heteroaliphatic; ring system" preferably a (C3-C8)cycioalkyl radical in which at least one carbon unit is replaced by 0, S or a group NR' and R' is hycrogen, (C:-C4)alkyl, (CrC4)aikanoyl, (C--Cl)aikoxycarbcnyl, (C^CJalkylsulfonyl, (C The substituents with which the various aliphatic, cycicaiiphatic, aromatic and heterocyclic ring systems can be provided are. for example, halogen, nitro, cyano, di-(CrC4)alkylamino, (C1-C4)alkyl] (C3-C3)cycloaikyi, (Ci-CJtrialkyisilyl, (C1-C4)alkoxy, (CrC4)alkoxy-(CrC4)alkyl, (CrC2)alkoxy-[CH-CH:0]c:-ethcxy? (C.-CJaikylthio, (Cr Cu)alkylsulfinyl, (C,-C4)alkylsulfonyl, phenyl, benzyl, phenoxy, halophenoxy, (Cr C4)alkylphenoxy? (CrC4)alkoxyphenoxy, phenylthio. heterocyclyl, heterocyclylthio or heterocyclyloxy, it being possible for one or more, in the case of fluorine also up to the maximum number of, hydrogen atoms in the alky! radicals and the radicals derived therefrom to be replaced by halogen, preferably chlorine or fluorine, where, in the event that these substituents are (C.-C^aikyi, they may also be linked cyclically and where one or two aliphatic careen units in these fused ring systems, such as, for example, the indane, di-, tetra- cr cecahycronaphthyl or benzocycloheptane system, may be replaced by hetercatom units such as oxygen or sulfur and where one or more, in the case cf nuenne also up to the maximum number cf, hydrogen atoms on the aliphatic carbon atom units can be replaced by halogen or (CrC4)alkyt. It is also to be understood that enantiomeric arc diastereomeric forms of the compounds of formulae (I) and salts thereof are embraced by the present invention. By the term non-emetic is meant a compound that cces not generally elicit emesis from the animal when a protective, preventative cr cleaning dose is administered to the animal. Sy the term emesis is meant vomiting. Generally an emetic substance elicits the said emesis in less than 24 hcu" a^te- ac~~:s::a::cr, preferably less than 3 hours, more preferably less than 2 hours. Generally when the compounds of the invention are administered to a population of animals, more than 70% of the animals are free of emesis, preferably more than 30%r most preferably more than 90%. Preferred compounds of the formula (I) are those wherein: R2C1 is cyano, C(0)alkyl, C(S)NH2, alkyl, C(=NOH)NH: cr C(=NNH2)NH2; R2Q2 is S(O)hR203, C2-C3 alkenyl, C2-C3 haloalkenyl, cycioalkyl, haiocycloalkyl, cycloalkyl-alkyl, C2-C3 alkynyl; R2C- E5 aiky' cr haioalkyl; R^ is -OH, R205O-, HC(0)0-, R205C(O)O-, R205OC(O)O-, NH2C(0)0-, R205NHC(O)O-, R2e5R2ceNC(O)O-tR205S(O)nC(O)O-; R2C5 is alkyl, haioalkyl, cycioalkyl, haiocycloalkyl, alkoxyalkyl, haioalkoxyalkyl, aminoaikyi, alkylaminoalkyl, diaikylaminoalkyl, haloalkylaminoalkyl, di(haloalkyl)aminoalkyl, R206 is alkyi, haioalkyl, cycioalkyl, haiocycloalkyl, alkoxyalkyl, haioalkoxyalkyl, or R205 and R206 may form together with the nitrogen to which they are attached a 3 to 7 membered ring which additionally may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur; X, is selected from nitrogen and C-R212; R2:1, R212 are independently selected from halogen, hydrogen, CN, and N02; R2,3 is selected from halogen, haioalkyl, haloalkoxy, -S(0).„CF2f and -SF5 r"\~-. is nvGrcGefi. and h, k and n are independently selected from 0, 1, and 2. Further compounds of formula (I) which are preferred according to the present invention are those wherein: R^, is cyano: Zs ic C//*\ \ O > ••2C2 -'\>™/yhl ^2C3* R2C3 is aikyi cr haioaikyi: R2rti is OH cr R—5O; X1 is selected from nitrogen and C-R212; R2, R213 is selected from halogen, haioalkyl, haloalkoxy, -S(0)kCF3, and -SF5; and h and k are independently selected from 0, 1, and 2. The compounds of formula (I) of the present invention preferably have one or more of the following features: R~n, is cvano; R^3 is haiorneihyl, preferably CF3; R211 and R212are independently halogen; X, is C-Rr2; R213 is halcalkyf, haioalkoxy or-SF5; or h is 0 or 1, or 2. A further embodiment of the invention includes compounds of the formula (I), with the proviso that if R201 is CM and R202 is S(O)hR203 then R2CM is not R205O or R2o5R2G6N-C(0)-0-. in another aspect of the present invention there is provided a method of controlling parasites in or on an animal by administering to the animal an 1-arylpyrazole of formula (II): •.vnerein: Rz, is cyano, C(=S)NH2l C(=NOH)NH: cr C(=NNH2)NH:; Rr is S(0)mR22; R22 is alkyl orhaloalkyl; R24 is OH, HC(0)0-, R25C(0)O-, R25OC(0)0-, R25R25-N-C(0)-0- or R25S(0)nC(0)0-; R:£ is alkyl, haioalkyl, cycioalkyl, halocycloalkyl, aikoxyalkyl, haloalkoxyalkyi, adamantyl, adamantyl, aminoalkyl, alkylamincalkyi, dialkyiamir.oalkyl, haioalkylaminoalkyl, di(haloa!kyl)aminoalkyi, aryl optionally substituted, hetaryl optionally substituted, arytalkyi optionally substituted, hetar/ialkyl optionally substituted, C2-C6 alkenyl, C2-C6 alkinyl; or two groups R25 may form together with the nitrogen to which they are attached a 3 to 7 membered ring which additionally may contain one or mere heteroatoms selected T'rom nitrogen, oxygen and sulfur; X is selected from nitrogen and C-R32; R3- and R32 are independently selected from halogen, hydrogen, CN, C--C3 alkyl and N02; R33 is selected from halogen, haioalkyl, haloaikoxy, -S(0)rCF3, and -SF5 or forms a ring together with R^ ; R34 is hydrogen or may constitute together with R2:3 a group of OCF20, CF2OCF2, CF2OCF20 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring; m is 0, 1 or 2; r is selected from 0, 1, and 2; and veterinarily acceptable salts thereof; provided that if R21 is cyano then R24 is not R2£R:5-N-C(0)-0-. Preferred are compounds of formula (II), wherein; RT_ is cyano, C(=S)NH2, C(=NOH)NH2 or C(=NNH2)NH:; r\22 ^ b\ J)Ti \22i \23 R:4 Is OH, HC(0)0-, R:5C(0)0-, R25OC(0)0- cr R^5Q;rC(0)0-; R:5 is alky!, haioalkyl, cycioalkyl, halocycloalkyl. aikoxyalkyl, haloalkoxyalkyi; X is selected from nitrogen and C-R32; R31 and R32 are independently selected from halogen, hydrogen, CM, C.-C3 alkyl and N02; R33 is selected from halogen, haloaikyi, haioaikoxy, -S(0).CF3, and ~SF5 in another aspect of the present invention there is provided a compound of formula (!!) or salt thereof as hereinbefore described with the proviso that the compound is not 1 -(2, 6-dichioro-4-trifluoromethylphenyi)-3-cyano-4-trifluoromethylthio-5-hycrcxypyrazole. A further preferred class of compounds of formula (I!) are those wherein: R2. is cyano; R^ is 8(0)^23; R^ is haloaikyi, preferably CF3; R24 is OH; X is selected from nitrogen and C-R32; R2: and R32 are independently selected from halogen, R^ is selected from halogen, haloaikyi, haioaikoxy, -S(CICF3, and -SF5; m and r are independently selected from 0, 1, and 2 with the proviso that the compound is not 1-(2t6-dichIcro-4-trifluoromethylphenyl)-3- cyar:C-4-trifluoromethylthio-5-hydroxypyrazole. in a further aspect of the invention the following groups of compounds are provicec: Compounds of the formula (I), wherein R:,, is C(0)NH2t C(O)NHR205, C(O)NR205R2C6, C(0)N=S(R2C3)~, haloaiky! or heterocyciyi from the group: coiionailv substituted by R^. Compounds of the formula (I), wherein R202 is nitro or imidazol-2-yl optionally substituted by alkyl, alkoxy, haioalkyl, halogen, cyano, nitro. Compounds of the formula (I), wherein * Rio- is R2C5S020-, aryi-S020-, (C4-C7)-oxacycioalkyioxy, R:c5R2c6N-C(NR205)-O-, -:c5-2csN-C(NH}-0- , R205NH-C(NR205)-O-, R2Q5NH-C(NH)-0-, R205N=CH-O-f R:c£N=C(R:ce)-0-, R2Q5NH-C(S)-0-, R205R2o6N-C(S)-0-. Compounds of the formula (I), wherein R214 constitute together with R2,3 a group of OCF20, CF.OCF,, CF2OCF20 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring. The compounds 1-(2,6-dichioro-4-trifluoromethylphenyl}-3-cyano-4-trifluromethylsulfinyl-5-hydroxypyrazoie and 1-(216-dichicro-4-trifluoromethylphenyl)-3-cyano-4-trifluromethylsulfonyl-5-hydroxypyrazoie are highly preferred compounds according to the invention. The following compounds of formula (!) are preferred according to the present invention as listed in Tables 1 to 3. The Compound Numbers are for identification purposes only. The following symbols are hereby defined: Me means methyl; Et means ethyl; n-Pr means n-propyt; i-Pr means iscprcpyi; n-Bu means n-Butyl; and Ph means Phenyl. Methods of Synthesis Method 1 The compounds of formula (I) and (II) with R2oa/R24 = OH and R22= SR23 can te synthesized by reacting 5-hydrcxypyrazoles with sulfenyichlorides with or without bases in organic solvents (see e.g. EP-A-295 117): Method 2 The compounds of formula (!) and (II) with R204/R24 = OH and R^ SR23 can be synthesized by reacting 5-hydrcxypyrazoles with disulfurdichloride. The resulting pyrazoledisuifides can be alkylated to yield 4-pyrazolsulfides (see e.g. EP-A-374 061, EP295117, C. Wakselman, J. Chem. Soc. Perkin Trans 1, 1992 3371-3375.; : Method 3 The compounds of formula (I) and (II) with R204/R24 = OH and R22= S(0)aR~: (a=1f2) can be synthesized by reacting pyrazolsulfides RC2= SR:3 with oxidizing agents like peroxy compounds (hydrogenperoxide, organic peroxides as peroxyaceticacic), halogenderivatives (like periodate salts) and others to obtain sulfoxides R1== SOR:3 and sulfones R^SO-R^ (see e.g. EP-A-295 117). in another aspect of the present invention, compounds of formula (II) wherein R:4 is HC(0)0-, R25C(0)0-, R:5OC(0)0-( or R25S(0)nC(0)0 and R21, R^, R31, R23, X and n are defined above are generally prepared by reaction of compounds of formula (II) wherein R:4 is OH and R21I R32, R3,, R33, X and n are defined above with a compounds of formulae (III), (IV), (V), and (V!) respectively wherein X2 is a leaving group such as a halogen atom or an acetyl group: HC(0)X: R25C(0)X2 R25OC(0)X2 R25S(0)nC(0)X2 (HI) (IV) (V) (VI) Compounds of general formula (II) wherein of formula (II) wherein R24 is OH and R2,t R^, R3^. R23. X and n are defined above may be prepared by methods known in the art generally or by methods described in International Patent Publications WO 94/21606, WO 97/07102, WO 98/24767, WO 98/28277, WO 98/28278 and WO 98/28279, European Patent Application 385809, and United States Patent 5232940, 5047550 or other methods known to the person skilled in the art. The present invention also relates to a composition comprising a parasiticidally effective, substantially non-emetic amount of a compound of formula (I) or a salt thereof and an acceptable carrier. Acceptable carriers for the use of the compounds are generally known to the skilled addressee concerned with pest control in animals, particularly domestic animals, most preferably dogs or cats. The compositions which can be used in the invention can comprise generally from about 0.001 to 95% of the compound of formula (I) or a salt thereof. The remainder of the composition up to 100% comprises a carrier as well as generally various additives. In this specification and the accompanying claims, percentages are by weight. The diluted liquid formulations generally comprise from about 0.001 to about 3% of compound of formula (I) or a salt thereof, preferably from about 0.1 :c aocu: J.Z°'Z. Soiid formulations generally comprise from about 0.1 to about 8% of compound c-* formula (!) cr a salt thereof, preferably from about 0.5 to about 1.5%. Compositions for oral administration comprise one or more of the compounds of general formula (i) or salts thereof in association with veterinarily acceptable carriers or coatings and include, for example, tablets, pills, capsules, gels, drenches, medicated feeds, medicated drinking water, medicated dietary supplements, slow- release boluses or other slow-release devices intended to be retained within the gastro-intestinal tract. Any of these may incorporate the active ingredients contained within micro-capsules or coated with acid-labile or alkali-labile or other pharmaceutical^ acceptable enteric coatings. Feed premixes or concentrates containing compounds of the present invention for use in preparation of medicated diets, drinking water cr ether materials for consumption by animals may also be used. In a highly preferred embodiment, the compositions are administered postprandially, preferably from just after a meal to 2 hours after the meal. In a highly preferred embedment, there is provided a product which is readily chewed by the animal and which product does generally not allow human contamination when the product is provided to the animal by hand. The compounds of general formula (I) or salts thereof may be administered before, during or after meals. The compounds of general formula (I) or salts thereof may be mixed with a carrier ar.c/cr a foodstuff. According to the present invention the compound of formula (I) or a salt thereof is administered orally in a ccse to the animal in a dose range generally from 0.1 to 5C0 mg/kg of the compound cf formula (I) or a salt thereof per kilogram of animai body weight (mg/kg), preferaciy from 1 to 100 mg/kg, more preferably from 1 to 50 mg.-kg. even more preferably from 2 to 25 mg/kg, most preferably from 3 to 15 mg/kg According to the present invention, the frequency of treatment of the animai. preferably the domestic animal to be treated by the compound of formula (I) or a salt thereof is generally from about once per week to about once per year, preferaciy from about once ever/ twe weeks to about once every six months, mere preferaciy from about once every rwc weeks to once every three months, and most preferably from about once ever/ twe weeks to about ence every six weeks. Generally the animai to be treated is a domestic animal, preferably a domestic companion animai. Mere :'s'e^:'y the animal to be treated is a dog and/er a cat. Accordingly, in a preferred embodiment there is provided a method of controlling parasites in or on a cat comprising administering orally to the cat a parasiticaily effective, substantially ncn emetic amount of a 1-arylpyrazole of formula (I). In a further preferred embodiment there is provided a method of controlling parasites in or on a dog comprising administering orally to the dog a parasitically effective, substantially non emetic amount of a 1-ar/lpyrazole of formula (I). The present invention also relates tc a ccmpositicn comprising a parasiticidally effective amount of a compound of formula (II) or a salt thereof and an acceptable carrier. Acceptable carriers for the use of the compounds are generally known to the skilled addressee concerned with pest control in animals, particularly domestic animals, most preferably dogs or cats. In another aspect of the present invention, the compounds of formula (II) or salts thereof may be used in the field of veterinary medicine or livestock husbandry or in the maintenance of public health against arthropods, helminths or protozoa which are parasitic internally or externally upon vertebrates, particularly warm-blooded vertebrates, for example domestic animals, e.g. cattle, sheep, goats, equines, swine, poultry, dogs or cats. The compounds to animals infested by or exposed to infestation by arthropods, helminths or protozoa, by parenteral, crai or topical application of compositions in which the active ingredient exhibits an immediate and/or prolonged action over a period of time against the anhropccs, helminths or protozoa, for example by incorporation in feed or suitable orally-ingestible pharmaceutical formulations, edible baits, salt licks, dietary supplements, pour-on formulations, sprays, baths, dips, showers, jets, dusts, greases, shampoos, creams, wax smears or livestock self-treatment systems. Solid or liquid compositions fcr application topically to animals, timber, stored products or household goods usuaiiy contain from about 0.00005% to about 90%, more particularly from about 0.001% to about 10%, by weight of one or mere compounds of formula (II) or veterinariiy acceptable salts thereof. For administration to animais orally or parenteral^/, including percutaneously solid or liquid compositions, these normally contain from about 0.1% to about 90% by weight of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. Medicated feedstuffs normally contain from about 0.001 % to about 3% by weight of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. Concentrates or supplements for mixing with feedstuffs normally contain from about 5% to about 90%T preferably from about 5% to about 50%, by weight of one or mere compounds of formula (II) or veterinariiy acceptable salts thereof. Mineral salt licks normally contain from about 0.1 % to about 10% by weight of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. Dusts or liquid compositions for application to livestock, goods, premises or outdoor areas may contain from about G.GG01 % to about 15%, more especially from about 0.005% to about 2.0%, by weight, of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. Suitable concentrations in treated waters are between about 0.0001 ppm and about 20 ppm, more particularly about 0.001 ppm to about 5.0 ppm. of one or more compounds of formula (II), or veterinariiy acceptable salts thereof, and may be used therapeutically in fish farming with appropriate exposure times. Edible baits may contain from about 0.01% to about 5%, preferably from about 0.01 % to about 1.0%, by weight, of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. When administered to vertebrates oarenterally, orally or by percutaneous or other means, the dosage of compounds of formula (II), or veterinariiy acceptable salts thereof, will depend upon the species, age, or health of the vertebrate and upon the nature and degree of its actual or potential infestation by arthropod, helminth or protozoan pests. A single dose of about 0.1 to about 500, preferably from 0.1 to about 100 mg, preferably about 2.0 to about 20.0 mg, per kg body weight of the animal or doses of about 0.01 to about 20.0 mg, preferably about 0.1 to about 5.0 mg, per kg body weight of the animal per day, for sustained medication, are generally suitable by orai or parenteral administration. By use of sustained release formulations or devices, the daily deses required over a perlcd cf months may be combined and administered to animals on a sinale occasion. The compounds of the invention may be administered most advantageously with another parasiticidalty effective material, such as an endoparasiticide, and/or an ectoparasiticide, and/or an endectoparasiticide. For example, such compounds include macrocyclic lactones such as avermeciins or milbemycins e.g., ivermectin; pyratel (generally adminsitered as pyrantel pamoate) or an insect growth regulator such as lufenuron or methoprene. By the term "parasites" as used in the specification and claims is meant endoparasites and ectoparasites of warm-blooded animals, particularly ectoparasites. Preferably, fleas and/cr ticks are controlled by the method of the present invention. Illustrative of specific parasites of various host animals which may be controlled by the methods of this invention include arthropods such as: Mites: Mesostigmata spp. e.g. mesostigmatids such as the chicken miteT Dermanyssus gallinae; itch or scab mites such as Sarcoptidae spp. for example Sarcoptes scabiei; mange mites such as Psoroptidae spp. including Chorioptes bovis and Psoroptes ovis; chiggers e.g. Trombiculidae spp. for example the north american chigger, Trombicula aifreddugesi; Ticks: e.g., soft-bcdied ticks including Argasidae spp. for example Argas spp. and Ornithodoros spp ; hard-bodied ticks including Ixodidae spp., for example Rhipicephalus sanguineus, and Bcophiius spp.; Lice: sucking lice, e.g., Menopon spp. and Bovicola spp.; biting lice, e.g.. Haematopinus spp., Linognathus spp. and Solenopotes spp.; Fleas: e.g., Ctenocephalides spp., such as dog flea (Ctenocephaiides canis) and cat flea (Ctenccephalides felis); Xencpsyila spp. such as oriental rat flea [Xencpsylia cheopis]; and Pulex spp. such as human flea [Pulex irritans]; True bugs: e.g., Cimicldae cr Including the common bed bug (Cimex iectularus :. Triatominae spp. inducing inaicmsd bugs aiso known as kissing bugs; for examole Rhodnius prolixus and Tristcms spp.; bloodsuckina adult flies: (e.c., horn fly THaematobia irrita.nsl, horse flv [Tabanus spp.], stable fly [Stomoxys calcitrans], black fly [Simulium spp.], deer fly [Chryscps spp.], louse fly [Meicphagus ovinus], tsetse fly [Glossina spp.], mosquitoes [Culex spp., Anopheles spp., and Aedes spp.); and parasitic fly maggots: (e.g., bot fly [Oestrus ovis and Cuterebra spp.], blow fly [Phaenicia spp.], screwworm [Cochliomyia hominivorax], cattle grub [Hypoderma spp.], fieeceworm. The present invention also provides for the use of a compound cf formula (I) or a salt thereof hereinbefore described as a therapeutic agent, preferably for animals, more preferably for domestic animals. The veterinary composition may be sterile or non-sterile. It may be a liquid (e.g. aqueous) or solid (e.g., dry) composition, in particular a freeze-dried composition, which, by addition of water or another liquid, orally effective solutions may be prepared. The present invention also provides for the use of a compound of formula (I) or a salt thereof as hereinbefore defined for the manufacture of a veterinary ccmoosition for the control of parasites in or on an animal. In a further embodiment of the invention there is provided the use cf a compound of formula (I) or salt thereof for controlling parasites in or on an animal without causing emesis of the animal. Preferred is the use forcraily administering the compound to the animal, which is preferably a domestic animal, highly preferred a cat or a dog. In a further embodiment of the invention there is provided the use of a compound of formula (I) or salt thereof for the manufacture of a substantially ncn emetic composition, for controlling parasites in cr en an animal, preferab'y ~er era! administerina. The present invention aisc relates to a method of cleaning anima.s •- coed health comprising the application to the animal of a compound of formula (!) cr a sait thereof as hereinbefore defined to the animal. The method of cleaning an animal is not a method of treatment by therapy of the animal body per se, because (a) the animal is in good health and requires no substantial treatment to correct a deficiency of health; (b) the cleaning of the animal is not intended to be done by veterinary personnel, but by persons interested in the cleaning of the animal; and (c) the purpose of such cleaning is to avoid unpleasant conditions for humans and the environment in which humans inhabit so as to not infest the said humans with arthropods carried by the animal. By "carrier" is meant an organic or inorganic material, which can be natural or synthetic, and which is associated with the compound and which facilitates its application to the animal. This carrier is thus generally inert and should be arthropocidally acceptable. The carrier can be solid (e.g., clay, silicates, silica, resins, wax.) or liquid (e.g., water, alcohols, ketones, oil solvents, polar aprotic solvents) An example of an oil solvent is corn oil. An example of a polar aprotic solvent is dimethyl sulfoxide. The compounds of the invention also have utility in the control of arthropod or nematode pests of plants. The active compound is generally applied to the locus in which arthropod or nematode infestation is to be controlled at a rate cf about 0.C05 kg to about 25 kg of active compound per hectare of locus treated, preferably 0.02 tc 2 kg/ha. Under ideal conditions, depending on the pest to be controlled, the lower rate may offer adequate protection. On the other hand, adverse weather conditions, resistance of the pest and other factors may require that the active ingredient be used in higher proportions. For foliar application, a rate cf 0.01 to 1 kg/ha may be used. When the pest is soil-borne, the formulation containing the active ccmpcur.c is distributed evenly over the area to be treated in any convenient manner. Application may be made, if desired, to the field or crop-growing area generally cr in close proximity to the seed or plant to be protected from attack. The active component can be washed into the soil by spraying with water over the area or can be left tc the natural action of rainfall. During or after application, the formulation can, if desired, be distributed mechanically in the soil, for example by ploughing or disking. Application can be prior to planting, at planting, after planting but before sprouting has taken place or after sprouting. The compounds of the invention may be applied in solid or liquid compositions to the soil principally to control those nematodes dwelling therein but also to the foliage principally to control those nematodes attacking the aerial parts of the plants The compounds of the invention are of value in controlling pests which feed on parts of the plant remcte from the point of application, e.g. leaf feeding insects are Killed by the subject compounds applied to roots. In addition the compounds may reduce attacks on the plant by means of antifeeding or repellent effects. The compounds of the invention are of particular value in the protection of field, forage, plantation, glasshouse, orchard and vineyard crops, or ornamentals and of plantation and forest trees, for example, cereals (such as maize, wheat, rice, sorghum), cotton, tobacco, vegetables and salads (such as beans, coie crops, curcurbits, lettuce, onions, tomatoes and peppers), field crops (such as potato, sugar beet, ground nuts, soyabean, oil seed rape), sugarcane, grassland and forage (such as maize, sorghum, lucerne), plantations (such as of tea, coffee, cocoa, banana, cii palm, coconut, rubber, spices), orchards and groves (such as of stone and pip fruit, citrus, kiwrfruit. avocado, mango, olives, and walnuts), vineyarcs, ornamental plants, flowers and shrubs under glass and in gardens and parks, forest trees (both deciduous and evergreen) in forests, plantations and nurseries. They are also valuable in the protection of timber (standing, felled, converted, stored or structural) from atiack by sawflies (e.g. urocerus) or beetles (e.g. scciytids, platypodidst lyciids, bcstrychids, cerambycids, anobiids), or termites, for example, reticulitermes szz., ^eteroteimes spp., coptotermes. They have applications in the protection of stored products such as grains, bruits, nuts, spices arc zz~szzc. whether whole, miiled or compounded into prccucts. from moth, beetle and mite attack. Also protected are stored animal products such as skins, hair, wool and feathers in natural or converted form (e.g. as carpets or textiles) from moth and beetle attack; also stored meat and fish from beetle, mite and fly attack. The disclosure in US provisional application No. 60/163658 from which this application claims priority is incorporated herein by reference. The invention is further illustrated by the fcilowing examples, without limiting it thereto. Examples and Preparations Example 1 Preparation of l-(2,6-Dichloro-4-trifluoromethylphenyl)- 3-cyano-4-trifiuoromethylsuIfinyl-5-hydroxypyrazole. To a solution of 15 g (35.5 mmol) of 1-(2t6-dichioro-4-trifluoromethylpheny[)-3-cyano-4-trifluoromethylsulfenyl-5-hydroxypyrazole in 125 ml of dichlcromethane at room temperature was added a solution of m-chioroperbenzoic acid (8.76 g, 70 %, 35.5 mmol) in 375 ml of dichloromehane. The resulting solution was stirred at room temperature for 17 hr. It was then concentrated and triturated with ethyl acetate and heptane(1:2). Upon filtration a soiid was obtained. This solid was dissolved in ethyl acetate and stirred with saturated sodium bicarbonate solution. Ther layers were separated and the aqueous layer was extracted with three times of ethyl acetate. The combined organic layer was dried (magnesium sulfate) and concentrated. Upon chromatographic purification via siiica cei column, a soiid (5.7 g, 13.01 mol, 37 %) was obtained as the desired product, mp 135-187d. Example 2 Preparation of 1-(2,5-Dichloro-4-trifiucrcmethyiphenyi)-3-cyano-4-trifiuoromethylsulfonyl-5-hydroxypyrazole. To the solution of 2 g (4.74 mmol) of 1-(2,6-dichloro-4trifiuoromethylphenyl)-3-cyano-4-trifluoromethyisulfenyl-5- hydroxypyrazole in 1,2-dichloroethane was added 1.83 ml (9.52 mmol, 35 % in acetic acid) of peracetic acid at room temperature. The resulting solution was heated up to 60 C for 9 hr. It was then cooled and concentrated to give 2.05 g of residue. Upon chromatographic purification via silica gel column eiuting with gradient solvent mixture (heptance/ethyl acetate), an oil (1.08 g, 2.38 mmol, 50.2 % yield ) was obtained as the desired product with 98 % HFLC puriety; F-NMR, -60.999 ppm (AR-CF3), -79.893 ppm (S02CF3). H-NMR, 8.18 ppm (s, 2 H). Example 3 Preparation of 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-amido-4-trifluoromethylsulfenyl-5-hydroxypyrazole. To the mixture of 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifIuoromethylsulfenyl-5-hydroxypyra2ole (3.0 g, 7.13 mmol) and concentrated sulfuric acid (3 ml) was heated at 100 C for 3 hr. The reaction mixture was cooled and poured into ice-water. A solid was collected via filtration and was washed with water. It was then vacuum dried to obtain a solid (2.88 g, 6.56 mmol, 92 % yield) with 98 % HPLC puriety, m. p. 197-198 C. Example 4 Preparation of 1-{2,6-dichicrc4-trifluoromethyiphenyI)-3-thioamido-4-trifluoromethylsuIfenyl-5-hycroxypyrazole. To the mixture of 1-{2,6-dichloro-4- trifluoromethylphenyl)-3-amidc-44rifluoromethylsuif9ny!-5-hydroxypyrazole (1 g, 2.28 mmol) and Lawesson's reagent (0.49 g, 1,21 rnrnoi) in toluene was heated up to reflux for 4 hr. The reaction r.ixture turned into a solution during this time. This solution was then cooled , concentrated, and via chromatographic purification to provide a solid (0.283 g, 0.623 mmol, 27.3 % yield) with 96 % HPLC puriety m. p. 150-151 decomp. Example 5 Preparation of 1 -(2f6-Dichloro-4-trifluoromethylphenyl)-3-oxirnicamido-4- trifluoromethylsulfenyl-5-hydroxypyrazoie. To the solution of 1-(2,6-dichioro-4- trifIuoromethylphenyl)-3-cyano^trifluoromethy!sulfeny!-5-hyd (3.0 g, 7.11 mmoi) in 15 ml of methanol at room temperature was added hydroxyamine hydrochloride (0.59 g, 8.53 mmoi) and triethyiamine (0.94 g, 9.24 mmol). The resulting mixture was stirred at room temperature for a total of 48 hr with additional hydroxyamine hydrochloride (I.ISg, 17.06 mmol) and triethyiamine (1.88 g, 18.5 mmol) added portionwise. The resulting reaction mixture was concentrated and then dissolved in ethyl acetate. The organic layer was washed with saturated ammonium chloride, water.dried (sodium sulfate), concentrated to give a brown oil which solidified after standing, m. p. 184 C. Example 6 Preparation of 1 -(2,6-Dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulfenyl-5-trimethylacetoxypyra2ole. To the solution of 1-(2,6-dichioro-4-trifiuoromethylphenyl)-3-cyano-4-trifluorcmethylsulfenyl-5-hydroxypyrazole (7.00 g, 16.6 mmol) and pyridine (4.91 g, 62.1 mmcl) in 1,2-dichicroethane at room temperature was added trimethyiacetyi chloride (4.37 g, 26.2 mmol) dropwise. Ice bath was used to maintain the temperature of the reaction. After 20 hr at room temperature, the orgainc layer was washed with five times of aqueous KHS04 tii! the aqueous solution was at pH 1. The orgainc layer was then dried (Mg S04) and concentrated to aive a solid residue. User, chromatccrachic purification via silica eel column of the soiid residue, after trituration with pentane. a off white solid (2.403 c, 23.6 % yield, 97.0 % HPLC puriety) was provided as the desired product, m. p. 82-83 C. Example 7 Preparation of 1-(2,6-dichloro-4-trifluoromethyfphenyl)-3-cyano-4-chlorodifluoromethylsulfenyl-5-hydroxypyrazole. To the solution of 1-(2,6-dichloro-4-triilucromethylphenyl)-3-cyano-5-hydroxypyrazole (12.0 g. 37.3 mmol.) and pyridine (3.25 g, 41.0 mmol) in dichloromethane at -50- -60 C was added chiorodifluoromethanesuifenyl chloride (8.1 g, 46.6 mmol). Tr.e resulting solution was gradually warmed up to room temperature. After 20 hr, the organic layer was washed five times with water. It was then washed with brine and dried (Na2S04) to provide an oil. Upon chromatographic purification of the oil, a total of 11.6 g (26.4 mmol., 71 % yield) of the desired product with 97 % HPLC puriety was isolated. F-NMR: -30.05 ppm (CCIF2), -63.80 ppm (ArCF3). Biological Example The compounds 1-(2I6-dichloro-4-trifluoromethylphenyl)-3-cyanc-4-trifIuromethylthio-5-hydroxypyrazole, 1-(2,6-dichloro-4-trifluoromethylphenylr3-cyano-4-trifiuromethylsulfinyi-5-hydroxypyrazcie and 1-(2,6-dichloro-4-trifiuoromethylphenyl)-3-cyano-4-trtfluromethylsulfonyl-5-hydroxypyrazoie are formulated as a 30 mg/mL formulations in a 1:1 volume/volume solution of dimethyl sulfoxide and corn oil. Using this formulation, mixed breed dogs and cats are treated a: a rate of 10 mg of the compound per kg (mg/kg)of body weight of the dog and 20 mg/kg of the cat treated. The animals are fasted for at least 8 hours prior to -jeainent fed half cf the daiiy ration immediately prior to treatment, then allowed access to the remainder of the daiiy ration immediately following treatment. All dogs are infested with cat fleas (Ctenocephalides feiis) and with ticks (Rhipicephaius sanguineus) 1 day prior to administration of the compound. Cats are oniy infested with fleas. The initial flea and tick counts are performed 1 day after the administration of the compounds. At 7, 14, 21 and 28 days after treatment the dogs are re-infested with ticks and 8, 15, 22 and 29 days after treatment the dogs and cats are re-infested with fleas. At 1, 9, 16f 23 and 30 days after treatment the control of fleas and ticks in treated dogs and cats is determined versus a group of infested dogs and cats which receive a placebo consisting of a 1:1 volume/volume solution of dimethyl sulfoxide and corn oil. To determine the efficacies of the compounds, the arthropods are combea from the animals and counted. Satisfactory results are obtained for many of the above-mentioned compounds in any of the three areas of evaluation without any significant side effect for a period ranging from eight to thirty days: control of flea on dogt control of tick on dog, and control of flea on cat. They are: 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4- trifluoromethylsulfenyl-5-trimethylacetoxypyra20le 3-10 , 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifiuoromethylsulfenyl-5-ethoxypyrazole 3-1. 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-chlorodifluoromethyisulfenyl-5-hydroxypyrazole 1-9 , 1-(2?6-dichloro-4-trifIuoromethylphenyl)-3-cyano-4-trifluorornethyisulfenyl-5-hydroxypyrazoie 1-1 , 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyisulfonyl-5-hydroxypyrazole 1-5, 1-(2?6-dichloro-4-thfluoromethylphenyl)-3-cyano-4-tnfluoromethylsulfinyl-5-hydroxypyrazole 1-3 , 1-(2,6-dichioro-4-trifiuormethyi(phenyl)-3-cyano-4-trifluonmethylsulfonyl-5-N,N-dimethylcarbamyloxypyrazoie 19-1. CLAIMS 1. A method of controlling parasites in or on an animal comprising administering to the animal a parasiticidaily effective, substantially non-emetic amount of a 1-arylpyrazoie cf formula (I): wherein: R20, is cyar.c, C(0)alkyl, C(S)NH2, C(NH)OR203, C(NH)SR203, alkyi, C(=NOH)NH2, C(=NNH2)NH2. C(0)NH2, C(O)NHR205, C(O)NR205R2C6l haloalkyl or heterocyclyl from the group: optionally substituted by R^,; R:02 is Si'C^R^., C:-C5 alkeny!, C2-C5 haioaikenyi, cycicalkyl, haiccycicalkyl. cycioaikyi-alkyi , C2-CQ aikynyi, nitro or imidazoi-2-yi optionally substituted by alkyl, aikcxy, ha!ca:kyi, halogen, cyano and/or nitro; R2C3 is aikyi or haloalkyl; R:C4 is -OH. R2Q50-, HC(0)0-, R205C(O)O-, R205OC(O)O-, NH2C(0)0-, R205NHC(O)O-, R:osR:o6NC(0)0-, R2a£S(0)nC(0)C-, R2C6S020-, aryl-S02CK (CrC7)-oxacyc!oalkyloxy, R2o5R206N-C(NR205)-0-, R2C5R206N-C(NH)-O-, R2C5NH.C(NR:c5)-0., R205NH-C(NH)-O-, R2G5N=CH-0-, R205N=C(R2C6)-O-, R205NH-C(S)-O-, R2C5R206N-C(S)-O-; R^ is alkyi, haloaikyl, cycicalkyi, halocycioaikyl, alkoxyalkyl, haloalkoxyalkyl, adamantyl, aminoalkyt, alkyiaminoaikyi, dialkylaminoalkyl, haloalkylaminoalkyl, di(haioalkyl)aminoalkyl, aryi optionally substituted, hetaryi optionally substituted, aryiaikyl optionally substituted, hetarylalkyl optionally substituted, C2-C6 alkenyi, C2- C5 alkinyl; R206 is alky!, haloaikyl, cycioalkyl, halocycScaikyi. alkoxyalkyl, haloalkoxyalkyl, an/1 optionally substituted, hetaryi optionally substituted, arylalkyl optionally substituted, hetarylalkyl optionally substituted; or R205 and R2C6 may form together with the nitrogen to which they are attached a 3 to 7 membered ring which additionally may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur X, is selected from nitrogen and C-R212; R2,,, R212 are independently selected from halogen, hydrogen, CNT (VC3 alkyi and N02; R213 is selected from halogen, haloaikyl, haloaikoxy, -S(0)kCF3, and -SF5 or forms a ring with R21A; R214 is hydrogen or may constitute together with R213 a group of OCF20, CF2OCF2, CF2OCF20 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring; and h, k and n are independently selected from 0, 1. and 2; and veterinariiy acceptable salts thereof. 2. A method of controiiina parasites in or on an animal as claimed in claim 1 bv administering to the animal an 1-ary!pyrazcie cf formula (II): wherein: R21 is cyano, C(=S)NH2, C(=NOH)NH, or C(=NNH2)NH2; R22 's S(0)mR23; R23 is alkyi or haloalkyi; R24 is OH, HC(0)0-, R25C(0)0-, R25OC(0)0- or R25S(0)nC(0)0- R25 is alkyi, haloalkyi, cycloalkyl, halocycloalkyl, alkoxyalkyl, haloalkoxyalkyl, adamantyl, adamantyl, aminoalkyl, alkyiaminoalkyi, dialkylaminoalkyl, haloalkylaminoalkyl, di(haloaIkyi)aminoalkyl, aryi optionally substituted, hetaryl optionally substituted, arylalkyl optionally substituted, hetarylalkyl optionally substituted, C2-Cs alksnyi, C2-C6 alkinyl, or two groups R25 may form together with the nitrogen to which they are attached a 3 to 7 membered ring which additionally may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur; X is selected from nitrogen and C-R32; R31 and R32 are independently selected from halogen, hydrogen, CN, CrC3 alkyi and N02; R33 is selected from haicgen, haloalkyi, haloalkcxy, -S(0)rCF3, and -SF5 or forms a ring together with R^ ; R^ is hydrogen or may constitute together with R213 a group of OCF20, CF2OCF2, CF2OCF20 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring; m is 0, 1 or 2; r is selected from 0, 1, and 2; and veterinarily acceptable salts thereof; provided that if R:1 is cyano then R24 is not R25R25-N-C(0)-O. 3. A compound of formula (II) or salt there of as hereinbefore described in claim 2 with the proviso that the compound is not 1-(2,6-dichioro-4-trifluorcmethylphenyl)-3-cyano-4-trifluoromethylthio-5-hydroxypyrazole. 4. A compound according to claim 3 wherein R21 is cyano; Re is S(0)mR23; R23 is haloalkyi, preferably CF3; R24isOH; X is selected from nitrogen and C-R3:; R31 and R32 are independently selected from halogen, R33 is selected from halogen, haloalkyi, hsioaikoxy, -S(0)fCF3, and -SF5; m and r are independently selected from 0, 1, and 2. 5. The compound of formula (!) as defined in Claim 1 or the compound of formula (II) as defined in any one of ciaims 2,3 or 4 which is 1-(2f6-dichloro-4-trifIuoromethylphenyl)-3-cyano-4-trifturomethyisulfinyi-5-hydroxypyrazole. 6. The compound of formula (I) as defined in Claim 1 or the compound of formula (II) as defined in any one of ciaims 2,3 or 4 which is 1-(2,6-dichloro-4-trifIuoromethylphenyl)-3-cyano-4-trifIurcmethylsulfonyl-5-hydroxypyrazole. 7. A composition comprising a parasiticida!!y effective, amount of a compound of formula (I) or (II) or a salt thereof as defined ;n any one of the foregoing ciaims and an acceptable carrier. 8. A composition comprising a parasiticidally effective, amount of a compound of formula (II) or a salt thereof and an acceptable carrier as defined in any one of ciaims 2, 3,4, 5 or 6. 9. The method according to claims 1 wherein the animal is a domestic animal. 10. The method according to claim 1 wherein the 1-aryipyrazoie is administered orally in a dose to the animai in a dose range from 0.1 to 500 mg/kg. 11. A compound of formula (I) according to claim 1 wherein R201 is cyano, C(0)alkyl, C(S)NH2, C(NH)OR203, C(NH)SR2C3, alkylT C(=NOH)NH2, C(=NNH2)NH2, C(0)NH2, C(O)NHR205; C(O)NR205R2C6, haicaikyi or heterocyclyl from the group: optionally substituted by R203; and/or R202 is S(O)hR203, C2-C6 aikenyl, C2-C6 haloalkenyl, cyclcalkyl, halocycloalkyl, cycioalkyl-alkyl, C2-C6 alkynyl, nitro or imidazol-2-yl opticraily substituted by alkyl, aikoxy, haioalkyl, halogen, cyano and/or nitro; and/or R:c, is -OH, R2G50-, HC(0)0-, R205C(O)O-, R205OC(O)O-, NH2C(0)0-. R:o5NKC(0)0~, ^205^206^^(0)0-, R2csS(0)nC(0)0-, R206SO2O-P aryl-SG-C-, (0,-C7)-oxacycicaiky!oxy, Rzo5R2o6N-C(NR205)-0-1 R2a5R2c6N-C(NH)-0- , R2C£NH-C(NR2C5;-0-, R2C5NH-C(NH)-0-, R205N=CH-O-, R20SN=C(R2D6)-O-1 R2C5MH-C(S)-0^, R^c-R^N-C^O- ; and/or R:14 constitutes together with R213 a group of OCF20, CF2OCF2l CF2OCF20 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring; 12. The use of a compound of formula (i) according to claim 1 for controlling parasites in animals. 13. A method of controlling parasites in or on an animal substantially as lierein described and exemplified. 14. A composition substantially as herein described and exemplified.

Full Text

Control of Arthropods in Animals
Tre present invention relates to a method of control of parasites in animals, compositions comprising a compound effective for the sale control and compounds effective against parasites.
!t is generally a goal of agronomists and veterinarians to possess sufficient means to
con™i pests, particularly arthropods, when they attempt to invade or attack
mammais, particularly domestic animals and/ or livestock. A c;assical method of
controlling such pests has been the use of topical and/or systemic pesticides on or in
the domestic animal which is being attacked. Generally effective treatments include
the oral administration of insect growth regulators, such as lufenuron, or antiheiminth
compounds such as an ivermectin or an avermectin, or the topical application of the
insecticide fipronil. It is advantageous to apply pesticides tc animals in oral form so
as tc prevent the possible contamination of humans or the surrounding environment.
!t is an object of the present invention to provide new pesticides which may be used
in domestic animals.
Another object of the invention is to provide safer pesticides for domestic animals.
Another object of the invention Is to provide new pesticioes for domestic animais that
.•ray be used in lower doses than existing pesticides.
These objects are met in whole or in part by the present invention.
US 5,079,370, EP-A 0,846,686, WO 98/24769 and WO 97/23126 disclose the use of
sr/ipyrazoles as parasiticidai agents. However, these references are completely
silent on the problem that anti parasitical agents cften elicit emesis in the animal to
be protected or cured from the parasites.
The cresert invention crevices a method of ccntrcilinc sarasliss in or en an animai
com^nsing administering, preferably orally, tc the animal a oarasiticidaily effective.
substantially non-emetic amount of a l-aryipyrazcie of formula (!}:

wherein:
R20, is cyano, C(0)aikyl, C(S)NH2, C(NH)OR203, C(NH)SR2C3, alkyl, C(=NOH)NH2, C(=NNH2)NH2, C(0)NH2, C(O)NHR205, C(O)NR205R2C6l haioalkyl or heterocyciyl from the group:

optionally substituted by R203;
R202 is S(O)hR203, C2-C6 aikenyl, C2-C6 haloalkenyi. cycicalkyi, halocycloalkyi,
cycloalkyl-alky! , C2-C5 alkynylT nitro or imidazol-2-yl optionally substituted by alkyl,
alkoxy, haioalkyl, halogen, cyano and/or nitro;
R2C3 is aikyl or haioalkyl;
R2C4 is -OH, RajsO-, HC(0)O, R205C(O)O-, R20£OC(O)O-, NH2C(0)0-, R2C5NHC(0)0-I
RzosRsceNCCOJO-, R2C5S(0)RC(0)0-, R206SO2O-, aryl-SO:0-, (C4-C7)-oxacycioalkyloxy,
R^R-eN-aNR^J-O-, RM5R206N-C(NH)-O- , R^NH-CiNR-^rC-. R^NH-CfNHVO-.
R205N=CH-O-. R2«N=C(R206)-0-f R205NH-C(S)-O-( R2C5R:C£N-C(S)-C- ;
R:c5 is alkyl, haioalkyl, cycloalkyi, halocycloalkyi, aikoxyaikyi, haicaikoxyaikyl,
adarnantyl, aminoalkyl, alkylaminoalkyl, dialkyiaminoaikyl, haloalkylaminoalkyi,
di(haloalkyl)aminoalkyl, aryl optionally substituted, hetaryl optionally substituted,

arylaikyl optionally substituted, hetarylalkyi optionally substituted, C2-Cfi alkenyl, C2-
C5 alkinyl;
R:c6 is aikyi, haicalkyl, cycioalkyi, halocycioaikyl, aikoxyaikyl, haioaikcxyalkyi, aryl
optionally substituted, hetaryl optionally substituted, arylaikyl optionally substituted,
hetarylalkyi optionally substituted;
or R2C5 ar.c R206 may fcrm together with the nitrogen to which they are attached a 3 to
7 membered ring which additionally may contain one or more heteroatoms selected
from nitrogen, oxygen and sulfur;
X- is selected from nitrogen and C-R212;
R:-,f R2,2 are independently selected from halogen, hydrogen, CN, C,-C3 alkyl and
NO:;
R2-3 is selected from halogen, haloalkyl, haloalkoxy, -S(0)kCF3, and -SF5 or forms a
ring with R2«4;
R2.4 is hydrogen or may constitute together with R213 a group of OCF20, CF2OCF2,
CF.OCF-0 and CF2CF20, which forms together with the carbons they are attached
to a five to six membered ring;
and
h. k and r. are independently selected from 0, 1, and 2;
am* vciDMidM;jy aooe^uauic SCJUO uicreoi.
By the term "veterinarily acceptable salts" is meant salts the anions of which are
known and accepted in the art for the formation of salts for veterinary use. Suitable
acic addition salts, e.g. formed by compounds of formula (i) containing a basic
nitrogen atom, e.g. an amino group, include salts with inorganic acids, for example
hydrochlorides, sulphates, phosphates and nitrates and salts with organic acids for
exsmcie acetic aciu.
When R-. is OH the cvrazoie structure can also be exhibited bv its tautomeric forr':
as cvrazcicn structure.
Uniess otherwise specified, alkyl and alkoxy groups are straight chain or branched
and are generally lower alkyl and alkoxy groups, that is having from one to six
carbon atoms, preferably from one to four carbon atoms. Generally, the haicalkyl,

haloalkoxy and haioaikylamino groups have from one to four carbon atoms. Halogen
means F, CI, Br, and I, preferably F and CI. The haloaikyl and haloalkoxy and
haioaikylamino groups can bear one or more halogen atoms; preferred groups of
this type include -CF3 and -OCF3. Cycioaikyl groups generally have from 3 to 6
carbon atoms, preferably from 3 to 5 carbon atoms and may be substituted by one
or more halogen atoms. Preferably in compounds of formula (I), alkyl groups are
generally substituted by from one to five halogen atoms, preferably from one to three
halogen atoms. Chlorine and fluorine atoms are preferred.
In compounds of formula (I) the following examples of radicals are provided:
An example of cycioalkylalkyi is cyclopropylmethyl;
an example of cycioalkoxy is cyclopropyloxy;and
an example of alkoxyalkyl is CH3OCH2~.
Generally, in diaikylamino ordi(haloalkyl)amino radicals, the alkyl and haloaikyl
groups on nitrogen may be chosen independently of one another.
Generally, the term "aryl" means a carbocyclic aromatic radical having preferably 6
to 14, in particular 6 to 12, carbon atoms, for example phenyl, naphthyl or biphenyiyl,
preferably phenyl;
the term "heterocyclyi" preferably a hetaryl or heteroaliphatic ring system, "hetaryl"
preferably being understood as meaning an aryl radical in which at least one CH
group is replaced by N and/or at least two adjacent CH groups are replaced by S,
NH or O, for example a radical of thiophene, furan, pyrrole, thiazole, oxazole,
imidazole, isothiazole, isoxazoie, pyrazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,3,4-
triazole, 1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,3,4-
tetrazole, benzo[b]thicphene, benzo[b]furan, indole, benzo[c]thiophene,
benzo[c]furan, isoindole, benzoxazole, benzcthiazole, benzimidazole,
benzisoxazcie, benziscthiazole, benzcpyrazcie, benzothiatiiazole, benzotriazole,
dibenzofuran, dibenzcthicphene, carbazoie, pyridine, pyrazine, pyrimidine,
pyridazine, 1,3,5-triazine, 1,2,4-triazine, 1,2,4,5-triazine, quinoline, isoquinoiine,
quinoxaline, quinazoline, cinnoline, 1,8-naphthyridine, 1,5-naphthyridine,
1,6-naphthyridine, 1,7-naphthyridine, phthalazine, pyridopyrimidine, purine, pteridine
or4H-quinolizine;

and the term "heteroaliphatic; ring system" preferably a (C3-C8)cycioalkyl radical in which at least one carbon unit is replaced by 0, S or a group NR' and R' is hycrogen, (C:-C4)alkyl, (CrC4)aikanoyl, (C--Cl)aikoxycarbcnyl, (C^CJalkylsulfonyl, (C The substituents with which the various aliphatic, cycicaiiphatic, aromatic and heterocyclic ring systems can be provided are. for example, halogen, nitro, cyano, di-(CrC4)alkylamino, (C1-C4)alkyl] (C3-C3)cycloaikyi, (Ci-CJtrialkyisilyl, (C1-C4)alkoxy, (CrC4)alkoxy-(CrC4)alkyl, (CrC2)alkoxy-[CH-CH:0]c:-ethcxy? (C.-CJaikylthio, (Cr Cu)alkylsulfinyl, (C,-C4)alkylsulfonyl, phenyl, benzyl, phenoxy, halophenoxy, (Cr C4)alkylphenoxy? (CrC4)alkoxyphenoxy, phenylthio. heterocyclyl, heterocyclylthio or heterocyclyloxy, it being possible for one or more, in the case of fluorine also up to the maximum number of, hydrogen atoms in the alky! radicals and the radicals derived therefrom to be replaced by halogen, preferably chlorine or fluorine, where, in the event that these substituents are (C.-C^aikyi, they may also be linked cyclically and where one or two aliphatic careen units in these fused ring systems, such as, for example, the indane, di-, tetra- cr cecahycronaphthyl or benzocycloheptane system, may be replaced by hetercatom units such as oxygen or sulfur and where one or more, in the case cf nuenne also up to the maximum number cf, hydrogen atoms on the aliphatic carbon atom units can be replaced by halogen or (CrC4)alkyt.
It is also to be understood that enantiomeric arc diastereomeric forms of the compounds of formulae (I) and salts thereof are embraced by the present invention.
By the term non-emetic is meant a compound that cces not generally elicit emesis from the animal when a protective, preventative cr cleaning dose is administered to the animal. Sy the term emesis is meant vomiting. Generally an emetic substance elicits the said emesis in less than 24 hcu" a^te- ac~~:s::a::cr, preferably less than 3 hours, more preferably less than 2 hours. Generally when the compounds of the invention are administered to a population of animals, more than 70% of the animals are free of emesis, preferably more than 30%r most preferably more than 90%.

Preferred compounds of the formula (I) are those wherein:
R2C1 is cyano, C(0)alkyl, C(S)NH2, alkyl, C(=NOH)NH: cr C(=NNH2)NH2; R2Q2 is S(O)hR203, C2-C3 alkenyl, C2-C3 haloalkenyl, cycioalkyl, haiocycloalkyl, cycloalkyl-alkyl, C2-C3 alkynyl;
R2C- E5 aiky' cr haioalkyl;
R^ is -OH, R205O-, HC(0)0-, R205C(O)O-, R205OC(O)O-, NH2C(0)0-, R205NHC(O)O-,
R2e5R2ceNC(O)O-tR205S(O)nC(O)O-;
R2C5 is alkyl, haioalkyl, cycioalkyl, haiocycloalkyl, alkoxyalkyl, haioalkoxyalkyl,
aminoaikyi, alkylaminoalkyl, diaikylaminoalkyl, haloalkylaminoalkyl,
di(haloalkyl)aminoalkyl,
R206 is alkyi, haioalkyl, cycioalkyl, haiocycloalkyl, alkoxyalkyl, haioalkoxyalkyl,
or R205 and R206 may form together with the nitrogen to which they are attached a 3 to
7 membered ring which additionally may contain one or more heteroatoms selected
from nitrogen, oxygen and sulfur;
X, is selected from nitrogen and C-R212;
R2:1, R212 are independently selected from halogen, hydrogen, CN, and N02;
R2,3 is selected from halogen, haioalkyl, haloalkoxy, -S(0).„CF2f and -SF5
r"\~-. is nvGrcGefi.
and
h, k and n are independently selected from 0, 1, and 2.
Further compounds of formula (I) which are preferred according to the present invention are those wherein: R^, is cyano:
Zs ic C//**\ \ O
> ••2C2 *-'\>™/yhl ^2C3*
R2C3 is aikyi cr haioaikyi:
R2rti is OH cr R—5O;
X1 is selected from nitrogen and C-R212;
R2, R213 is selected from halogen, haioalkyl, haloalkoxy, -S(0)kCF3, and -SF5; and

h and k are independently selected from 0, 1, and 2.
The compounds of formula (I) of the present invention preferably have one or more
of the following features:
R~n, is cvano;
R^3 is haiorneihyl, preferably CF3;
R211 and R212are independently halogen;
X, is C-Rr2;
R213 is halcalkyf, haioalkoxy or-SF5; or
h is 0 or 1, or 2.
A further embodiment of the invention includes compounds of the formula (I), with the proviso that if R201 is CM and R202 is S(O)hR203 then R2CM is not R205O or R2o5R2G6N-C(0)-0-.
in another aspect of the present invention there is provided a method of controlling parasites in or on an animal by administering to the animal an 1-arylpyrazole of formula (II):

•.vnerein:
Rz, is cyano, C(=S)NH2l C(=NOH)NH: cr C(=NNH2)NH:;
Rr is S(0)mR22;
R22 is alkyl orhaloalkyl;

R24 is OH, HC(0)0-, R25C(0)O-, R25OC(0)0-, R25R25-N-C(0)-0- or R25S(0)nC(0)0-;
R:£ is alkyl, haioalkyl, cycioalkyl, halocycloalkyl, aikoxyalkyl, haloalkoxyalkyi,
adamantyl, adamantyl, aminoalkyl, alkylamincalkyi, dialkyiamir.oalkyl,
haioalkylaminoalkyl, di(haloa!kyl)aminoalkyi, aryl optionally substituted, hetaryl
optionally substituted, arytalkyi optionally substituted, hetar/ialkyl optionally
substituted, C2-C6 alkenyl, C2-C6 alkinyl;
or two groups R25 may form together with the nitrogen to which they are attached a 3
to 7 membered ring which additionally may contain one or mere heteroatoms
selected T'rom nitrogen, oxygen and sulfur;
X is selected from nitrogen and C-R32;
R3- and R32 are independently selected from halogen, hydrogen, CN, C--C3 alkyl and
N02;
R33 is selected from halogen, haioalkyl, haloaikoxy, -S(0)rCF3, and -SF5 or forms a
ring together with R^ ;
R34 is hydrogen or may constitute together with R2:3 a group of OCF20, CF2OCF2,
CF2OCF20 and CF2CF20, which forms together with the carbons they are attached
to a five to six membered ring;
m is 0, 1 or 2;
r is selected from 0, 1, and 2;
and veterinarily acceptable salts thereof;
provided that if R21 is cyano then R24 is not R2£R:5-N-C(0)-0-.
Preferred are compounds of formula (II),
wherein;
RT_ is cyano, C(=S)NH2, C(=NOH)NH2 or C(=NNH2)NH:;
r\22 *^ b\ J)Ti \22i \23 R:4 Is OH, HC(0)0-, R:5C(0)0-, R25OC(0)0- cr R^5*Q;rC(0)0-;
R:5 is alky!, haioalkyl, cycioalkyl, halocycloalkyl. aikoxyalkyl, haloalkoxyalkyi;
X is selected from nitrogen and C-R32;
R31 and R32 are independently selected from halogen, hydrogen, CM, C.-C3 alkyl and
N02;

R33 is selected from halogen, haloaikyi, haioaikoxy, -S(0).CF3, and ~SF5
in another aspect of the present invention there is provided a compound of formula (!!) or salt thereof as hereinbefore described with the proviso that the compound is not 1 -(2, 6-dichioro-4-trifluoromethylphenyi)-3-cyano-4-trifluoromethylthio-5-hycrcxypyrazole.
A further preferred class of compounds of formula (I!) are those wherein: R2. is cyano;
R^ is 8(0)^23;
R^ is haloaikyi, preferably CF3;
R24 is OH;
X is selected from nitrogen and C-R32;
R2: and R32 are independently selected from halogen,
R^ is selected from halogen, haloaikyi, haioaikoxy, -S(CICF3, and -SF5;
m and r are independently selected from 0, 1, and 2
with the proviso that the compound is not 1-(2t6-dichIcro-4-trifluoromethylphenyl)-3-
cyar:C-4-trifluoromethylthio-5-hydroxypyrazole.
in a further aspect of the invention the following groups of compounds are provicec: Compounds of the formula (I), wherein
R:,, is C(0)NH2t C(O)NHR205, C(O)NR205R2C6, C(0)N=S(R2C3)~, haloaiky! or heterocyciyi from the group:

coiionailv substituted by R^. Compounds of the formula (I), wherein

R202 is nitro or imidazol-2-yl optionally substituted by alkyl, alkoxy, haioalkyl, halogen, cyano, nitro.
Compounds of the formula (I), wherein
*
Rio- is R2C5S020-, aryi-S020-, (C4-C7)-oxacycioalkyioxy, R:c5R2c6N-C(NR205)-O-, -:c5-2csN-C(NH}-0- , R205NH-C(NR205)-O-, R2Q5NH-C(NH)-0-, R205N=CH-O-f R:c£N=C(R:ce)-0-, R2Q5NH-C(S)-0-, R205R2o6N-C(S)-0-.
Compounds of the formula (I), wherein
R214 constitute together with R2,3 a group of OCF20, CF.OCF,, CF2OCF20 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring.
The compounds 1-(2,6-dichioro-4-trifluoromethylphenyl}-3-cyano-4-trifluromethylsulfinyl-5-hydroxypyrazoie and 1-(216-dichicro-4-trifluoromethylphenyl)-3-cyano-4-trifluromethylsulfonyl-5-hydroxypyrazoie are highly preferred compounds according to the invention.
The following compounds of formula (!) are preferred according to the present invention as listed in Tables 1 to 3. The Compound Numbers are for identification purposes only. The following symbols are hereby defined: Me means methyl; Et means ethyl; n-Pr means n-propyt; i-Pr means iscprcpyi; n-Bu means n-Butyl; and Ph means Phenyl.

Methods of Synthesis Method 1
The compounds of formula (I) and (II) with R2oa/R24 = OH and R22= SR23 can te synthesized by reacting 5-hydrcxypyrazoles with sulfenyichlorides with or without bases in organic solvents (see e.g. EP-A-295 117):

Method 2
The compounds of formula (!) and (II) with R204/R24 = OH and R^ SR23 can be synthesized by reacting 5-hydrcxypyrazoles with disulfurdichloride. The resulting pyrazoledisuifides can be alkylated to yield 4-pyrazolsulfides (see e.g. EP-A-374 061, EP295117, C. Wakselman, J. Chem. Soc. Perkin Trans 1, 1992 3371-3375.; :

Method 3
The compounds of formula (I) and (II) with R204/R24 = OH and R22= S(0)aR~: (a=1f2) can be synthesized by reacting pyrazolsulfides RC2= SR:3 with oxidizing agents like peroxy compounds (hydrogenperoxide, organic peroxides as peroxyaceticacic), halogenderivatives (like periodate salts) and others to obtain sulfoxides R1== SOR:3 and sulfones R^SO-R^ (see e.g. EP-A-295 117).

in another aspect of the present invention, compounds of formula (II) wherein R:4 is HC(0)0-, R25C(0)0-, R:5OC(0)0-( or R25S(0)nC(0)0 and R21, R^, R31, R23, X and n are defined above are generally prepared by reaction of compounds of formula (II) wherein R:4 is OH and R21I R32, R3,, R33, X and n are defined above with a

compounds of formulae (III), (IV), (V), and (V!) respectively wherein X2 is a leaving group such as a halogen atom or an acetyl group:
HC(0)X: R25C(0)X2 R25OC(0)X2 R25S(0)nC(0)X2
(HI) (IV) (V) (VI)
Compounds of general formula (II) wherein of formula (II) wherein R24 is OH and R2,t R^, R3^. R23. X and n are defined above may be prepared by methods known in the art generally or by methods described in International Patent Publications WO 94/21606, WO 97/07102, WO 98/24767, WO 98/28277, WO 98/28278 and WO 98/28279, European Patent Application 385809, and United States Patent 5232940, 5047550 or other methods known to the person skilled in the art.
The present invention also relates to a composition comprising a parasiticidally effective, substantially non-emetic amount of a compound of formula (I) or a salt thereof and an acceptable carrier. Acceptable carriers for the use of the compounds are generally known to the skilled addressee concerned with pest control in animals, particularly domestic animals, most preferably dogs or cats. The compositions which can be used in the invention can comprise generally from about 0.001 to 95% of the compound of formula (I) or a salt thereof. The remainder of the composition up to 100% comprises a carrier as well as generally various additives. In this specification and the accompanying claims, percentages are by weight.
The diluted liquid formulations generally comprise from about 0.001 to about 3% of compound of formula (I) or a salt thereof, preferably from about 0.1 :c aocu: J.Z°'Z. Soiid formulations generally comprise from about 0.1 to about 8% of compound c-* formula (!) cr a salt thereof, preferably from about 0.5 to about 1.5%. Compositions for oral administration comprise one or more of the compounds of general formula (i) or salts thereof in association with veterinarily acceptable carriers or coatings and include, for example, tablets, pills, capsules, gels, drenches, medicated feeds, medicated drinking water, medicated dietary supplements, slow-

release boluses or other slow-release devices intended to be retained within the gastro-intestinal tract. Any of these may incorporate the active ingredients contained within micro-capsules or coated with acid-labile or alkali-labile or other pharmaceutical^ acceptable enteric coatings. Feed premixes or concentrates containing compounds of the present invention for use in preparation of medicated diets, drinking water cr ether materials for consumption by animals may also be used. In a highly preferred embodiment, the compositions are administered postprandially, preferably from just after a meal to 2 hours after the meal. In a highly preferred embedment, there is provided a product which is readily chewed by the animal and which product does generally not allow human contamination when the product is provided to the animal by hand. The compounds of general formula (I) or salts thereof may be administered before, during or after meals. The compounds of general formula (I) or salts thereof may be mixed with a carrier ar.c/cr a foodstuff.
According to the present invention the compound of formula (I) or a salt thereof is administered orally in a ccse to the animal in a dose range generally from 0.1 to 5C0 mg/kg of the compound cf formula (I) or a salt thereof per kilogram of animai body weight (mg/kg), preferaciy from 1 to 100 mg/kg, more preferably from 1 to 50 mg.-kg. even more preferably from 2 to 25 mg/kg, most preferably from 3 to 15 mg/kg According to the present invention, the frequency of treatment of the animai. preferably the domestic animal to be treated by the compound of formula (I) or a salt thereof is generally from about once per week to about once per year, preferaciy from about once ever/ twe weeks to about once every six months, mere preferaciy from about once every rwc weeks to once every three months, and most preferably from about once ever/ twe weeks to about ence every six weeks. Generally the animai to be treated is a domestic animal, preferably a domestic companion animai. Mere :'s'e^:'y the animal to be treated is a dog and/er a cat.
Accordingly, in a preferred embodiment there is provided a method of controlling parasites in or on a cat comprising administering orally to the cat a parasiticaily effective, substantially ncn emetic amount of a 1-arylpyrazole of formula (I).

In a further preferred embodiment there is provided a method of controlling parasites in or on a dog comprising administering orally to the dog a parasitically effective, substantially non emetic amount of a 1-ar/lpyrazole of formula (I).
The present invention also relates tc a ccmpositicn comprising a parasiticidally effective amount of a compound of formula (II) or a salt thereof and an acceptable carrier. Acceptable carriers for the use of the compounds are generally known to the skilled addressee concerned with pest control in animals, particularly domestic animals, most preferably dogs or cats.
In another aspect of the present invention, the compounds of formula (II) or salts thereof may be used in the field of veterinary medicine or livestock husbandry or in the maintenance of public health against arthropods, helminths or protozoa which are parasitic internally or externally upon vertebrates, particularly warm-blooded vertebrates, for example domestic animals, e.g. cattle, sheep, goats, equines, swine, poultry, dogs or cats.
The compounds to animals infested by or exposed to infestation by arthropods, helminths or protozoa, by parenteral, crai or topical application of compositions in which the active ingredient exhibits an immediate and/or prolonged action over a period of time against the anhropccs, helminths or protozoa, for example by incorporation in feed or suitable orally-ingestible pharmaceutical formulations, edible baits, salt licks, dietary supplements, pour-on formulations, sprays, baths, dips, showers, jets, dusts, greases, shampoos, creams, wax smears or livestock self-treatment systems.
Solid or liquid compositions fcr application topically to animals, timber, stored products or household goods usuaiiy contain from about 0.00005% to about 90%, more particularly from about 0.001% to about 10%, by weight of one or mere compounds of formula (II) or veterinariiy acceptable salts thereof. For administration to animais orally or parenteral^/, including percutaneously solid or liquid compositions, these normally contain from about 0.1% to about 90% by weight of one or more compounds of formula (II) or veterinariiy acceptable salts thereof.

Medicated feedstuffs normally contain from about 0.001 % to about 3% by weight of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. Concentrates or supplements for mixing with feedstuffs normally contain from about 5% to about 90%T preferably from about 5% to about 50%, by weight of one or mere compounds of formula (II) or veterinariiy acceptable salts thereof. Mineral salt licks normally contain from about 0.1 % to about 10% by weight of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. Dusts or liquid compositions for application to livestock, goods, premises or outdoor areas may contain from about G.GG01 % to about 15%, more especially from about 0.005% to about 2.0%, by weight, of one or more compounds of formula (II) or veterinariiy acceptable salts thereof. Suitable concentrations in treated waters are between about 0.0001 ppm and about 20 ppm, more particularly about 0.001 ppm to about 5.0 ppm. of one or more compounds of formula (II), or veterinariiy acceptable salts thereof, and may be used therapeutically in fish farming with appropriate exposure times. Edible baits may contain from about 0.01% to about 5%, preferably from about 0.01 % to about 1.0%, by weight, of one or more compounds of formula (II) or veterinariiy acceptable salts thereof.
When administered to vertebrates oarenterally, orally or by percutaneous or other means, the dosage of compounds of formula (II), or veterinariiy acceptable salts thereof, will depend upon the species, age, or health of the vertebrate and upon the nature and degree of its actual or potential infestation by arthropod, helminth or protozoan pests. A single dose of about 0.1 to about 500, preferably from 0.1 to about 100 mg, preferably about 2.0 to about 20.0 mg, per kg body weight of the animal or doses of about 0.01 to about 20.0 mg, preferably about 0.1 to about 5.0 mg, per kg body weight of the animal per day, for sustained medication, are generally suitable by orai or parenteral administration. By use of sustained release formulations or devices, the daily deses required over a perlcd cf months may be combined and administered to animals on a sinale occasion.
The compounds of the invention may be administered most advantageously with another parasiticidalty effective material, such as an endoparasiticide, and/or an

ectoparasiticide, and/or an endectoparasiticide. For example, such compounds include macrocyclic lactones such as avermeciins or milbemycins e.g., ivermectin; pyratel (generally adminsitered as pyrantel pamoate) or an insect growth regulator such as lufenuron or methoprene.
By the term "parasites" as used in the specification and claims is meant
endoparasites and ectoparasites of warm-blooded animals, particularly
ectoparasites. Preferably, fleas and/cr ticks are controlled by the method of the
present invention.
Illustrative of specific parasites of various host animals which may be controlled by
the methods of this invention include arthropods such as:
Mites: Mesostigmata spp. e.g. mesostigmatids such as the chicken miteT
Dermanyssus gallinae; itch or scab mites such as Sarcoptidae spp. for example
Sarcoptes scabiei; mange mites such as Psoroptidae spp. including Chorioptes
bovis and Psoroptes ovis; chiggers e.g. Trombiculidae spp. for example the north
american chigger, Trombicula aifreddugesi;
Ticks: e.g., soft-bcdied ticks including Argasidae spp. for example Argas spp. and
Ornithodoros spp ; hard-bodied ticks including Ixodidae spp., for example
Rhipicephalus sanguineus, and Bcophiius spp.;
Lice: sucking lice, e.g., Menopon spp. and Bovicola spp.; biting lice, e.g..
Haematopinus spp., Linognathus spp. and Solenopotes spp.;
Fleas: e.g., Ctenocephalides spp., such as dog flea (Ctenocephaiides canis) and cat
flea (Ctenccephalides felis); Xencpsyila spp. such as oriental rat flea [Xencpsylia
cheopis]; and Pulex spp. such as human flea [Pulex irritans];
True bugs: e.g., Cimicldae cr Including the common bed bug (Cimex iectularus :.
Triatominae spp. inducing inaicmsd bugs aiso known as kissing bugs; for examole
Rhodnius prolixus and Tristcms spp.;
bloodsuckina adult flies: (e.c., horn fly THaematobia irrita.nsl, horse flv [Tabanus
spp.], stable fly [Stomoxys calcitrans], black fly [Simulium spp.], deer fly [Chryscps
spp.], louse fly [Meicphagus ovinus], tsetse fly [Glossina spp.], mosquitoes [Culex
spp., Anopheles spp., and Aedes spp.); and

parasitic fly maggots: (e.g., bot fly [Oestrus ovis and Cuterebra spp.], blow fly [Phaenicia spp.], screwworm [Cochliomyia hominivorax], cattle grub [Hypoderma spp.], fieeceworm.
The present invention also provides for the use of a compound cf formula (I) or a salt
thereof hereinbefore described as a therapeutic agent, preferably for animals, more
preferably for domestic animals.
The veterinary composition may be sterile or non-sterile. It may be a liquid (e.g.
aqueous) or solid (e.g., dry) composition, in particular a freeze-dried composition,
which, by addition of water or another liquid, orally effective solutions may be
prepared.
The present invention also provides for the use of a compound of formula (I) or a salt
thereof as hereinbefore defined for the manufacture of a veterinary ccmoosition for
the control of parasites in or on an animal.
In a further embodiment of the invention there is provided the use cf a compound of formula (I) or salt thereof for controlling parasites in or on an animal without causing emesis of the animal.
Preferred is the use forcraily administering the compound to the animal, which is preferably a domestic animal, highly preferred a cat or a dog.
In a further embodiment of the invention there is provided the use of a compound of formula (I) or salt thereof for the manufacture of a substantially ncn emetic composition, for controlling parasites in cr en an animal, preferab'y ~er era!
administerina.
The present invention aisc relates to a method of cleaning anima.s •- coed health
comprising the application to the animal of a compound of formula (!) cr a sait
thereof as hereinbefore defined to the animal.
The method of cleaning an animal is not a method of treatment by therapy of the
animal body per se, because

(a) the animal is in good health and requires no substantial treatment to correct a deficiency of health;
(b) the cleaning of the animal is not intended to be done by veterinary personnel, but by persons interested in the cleaning of the animal; and
(c) the purpose of such cleaning is to avoid unpleasant conditions for humans and the environment in which humans inhabit so as to not infest the said humans with arthropods carried by the animal.
By "carrier" is meant an organic or inorganic material, which can be natural or synthetic, and which is associated with the compound and which facilitates its application to the animal. This carrier is thus generally inert and should be arthropocidally acceptable. The carrier can be solid (e.g., clay, silicates, silica, resins, wax.) or liquid (e.g., water, alcohols, ketones, oil solvents, polar aprotic solvents) An example of an oil solvent is corn oil. An example of a polar aprotic solvent is dimethyl sulfoxide.
The compounds of the invention also have utility in the control of arthropod or nematode pests of plants. The active compound is generally applied to the locus in which arthropod or nematode infestation is to be controlled at a rate cf about 0.C05 kg to about 25 kg of active compound per hectare of locus treated, preferably 0.02 tc 2 kg/ha. Under ideal conditions, depending on the pest to be controlled, the lower rate may offer adequate protection. On the other hand, adverse weather conditions, resistance of the pest and other factors may require that the active ingredient be used in higher proportions. For foliar application, a rate cf 0.01 to 1 kg/ha may be used.
When the pest is soil-borne, the formulation containing the active ccmpcur.c is distributed evenly over the area to be treated in any convenient manner. Application may be made, if desired, to the field or crop-growing area generally cr in close proximity to the seed or plant to be protected from attack. The active component can be washed into the soil by spraying with water over the area or can be left tc the natural action of rainfall. During or after application, the formulation can, if desired, be distributed mechanically in the soil, for example by ploughing or disking.

Application can be prior to planting, at planting, after planting but before sprouting has taken place or after sprouting.
The compounds of the invention may be applied in solid or liquid compositions to the soil principally to control those nematodes dwelling therein but also to the foliage principally to control those nematodes attacking the aerial parts of the plants The compounds of the invention are of value in controlling pests which feed on parts of the plant remcte from the point of application, e.g. leaf feeding insects are Killed by the subject compounds applied to roots. In addition the compounds may reduce attacks on the plant by means of antifeeding or repellent effects. The compounds of the invention are of particular value in the protection of field, forage, plantation, glasshouse, orchard and vineyard crops, or ornamentals and of plantation and forest trees, for example, cereals (such as maize, wheat, rice, sorghum), cotton, tobacco, vegetables and salads (such as beans, coie crops, curcurbits, lettuce, onions, tomatoes and peppers), field crops (such as potato, sugar beet, ground nuts, soyabean, oil seed rape), sugarcane, grassland and forage (such as maize, sorghum, lucerne), plantations (such as of tea, coffee, cocoa, banana, cii palm, coconut, rubber, spices), orchards and groves (such as of stone and pip fruit, citrus, kiwrfruit. avocado, mango, olives, and walnuts), vineyarcs, ornamental plants, flowers and shrubs under glass and in gardens and parks, forest trees (both deciduous and evergreen) in forests, plantations and nurseries. They are also valuable in the protection of timber (standing, felled, converted, stored or structural) from atiack by sawflies (e.g. urocerus) or beetles (e.g. scciytids, platypodidst lyciids, bcstrychids, cerambycids, anobiids), or termites, for example, reticulitermes szz., ^eteroteimes spp., coptotermes.
They have applications in the protection of stored products such as grains, bruits, nuts, spices arc zz~szzc. whether whole, miiled or compounded into prccucts. from moth, beetle and mite attack. Also protected are stored animal products such as skins, hair, wool and feathers in natural or converted form (e.g. as carpets or textiles) from moth and beetle attack; also stored meat and fish from beetle, mite and fly attack.

The disclosure in US provisional application No. 60/163658 from which this application claims priority is incorporated herein by reference.
The invention is further illustrated by the fcilowing examples, without limiting it thereto.
Examples and Preparations
Example 1
Preparation of l-(2,6-Dichloro-4-trifluoromethylphenyl)- 3-cyano-4-trifiuoromethylsuIfinyl-5-hydroxypyrazole. To a solution of 15 g (35.5 mmol) of 1-(2t6-dichioro-4-trifluoromethylpheny[)-3-cyano-4-trifluoromethylsulfenyl-5-hydroxypyrazole in 125 ml of dichlcromethane at room temperature was added a solution of m-chioroperbenzoic acid (8.76 g, 70 %, 35.5 mmol) in 375 ml of dichloromehane. The resulting solution was stirred at room temperature for 17 hr. It was then concentrated and triturated with ethyl acetate and heptane(1:2). Upon filtration a soiid was obtained. This solid was dissolved in ethyl acetate and stirred with saturated sodium bicarbonate solution. Ther layers were separated and the aqueous layer was extracted with three times of ethyl acetate. The combined organic layer was dried (magnesium sulfate) and concentrated. Upon chromatographic purification via siiica cei column, a soiid (5.7 g, 13.01 mol, 37 %) was obtained as the desired product, mp 135-187d.
Example 2
Preparation of 1-(2,5-Dichloro-4-trifiucrcmethyiphenyi)-3-cyano-4-trifiuoromethylsulfonyl-5-hydroxypyrazole. To the solution of 2 g (4.74 mmol) of 1-(2,6-dichloro-4trifiuoromethylphenyl)-3-cyano-4-trifluoromethyisulfenyl-5-

hydroxypyrazole in 1,2-dichloroethane was added 1.83 ml (9.52 mmol, 35 % in acetic acid) of peracetic acid at room temperature. The resulting solution was heated up to 60 C for 9 hr. It was then cooled and concentrated to give 2.05 g of residue. Upon chromatographic purification via silica gel column eiuting with gradient solvent mixture (heptance/ethyl acetate), an oil (1.08 g, 2.38 mmol, 50.2 % yield ) was obtained as the desired product with 98 % HFLC puriety; F-NMR, -60.999 ppm (AR-CF3), -79.893 ppm (S02CF3). H-NMR, 8.18 ppm (s, 2 H).
Example 3
Preparation of 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-amido-4-trifluoromethylsulfenyl-5-hydroxypyrazole. To the mixture of 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifIuoromethylsulfenyl-5-hydroxypyra2ole (3.0 g, 7.13 mmol) and concentrated sulfuric acid (3 ml) was heated at 100 C for 3 hr. The reaction mixture was cooled and poured into ice-water. A solid was collected via filtration and was washed with water. It was then vacuum dried to obtain a solid (2.88 g, 6.56 mmol, 92 % yield) with 98 % HPLC puriety, m. p. 197-198 C.
Example 4
Preparation of 1-{2,6-dichicrc4-trifluoromethyiphenyI)-3-thioamido-4-trifluoromethylsuIfenyl-5-hycroxypyrazole. To the mixture of 1-{2,6-dichloro-4-
trifluoromethylphenyl)-3-amidc-44rifluoromethylsuif9ny!-5-hydroxypyrazole (1 g, 2.28 mmol) and Lawesson's reagent (0.49 g, 1,21 rnrnoi) in toluene was heated up to reflux for 4 hr. The reaction r.ixture turned into a solution during this time. This solution was then cooled , concentrated, and via chromatographic purification to provide a solid (0.283 g, 0.623 mmol, 27.3 % yield) with 96 % HPLC puriety m. p. 150-151 decomp.

Example 5
Preparation of 1 -(2f6-Dichloro-4-trifluoromethylphenyl)-3-oxirnicamido-4-
trifluoromethylsulfenyl-5-hydroxypyrazoie. To the solution of 1-(2,6-dichioro-4-
trifIuoromethylphenyl)-3-cyano^trifluoromethy!sulfeny!-5-hyd (3.0 g,
7.11 mmoi) in 15 ml of methanol at room temperature was added hydroxyamine hydrochloride (0.59 g, 8.53 mmoi) and triethyiamine (0.94 g, 9.24 mmol). The resulting mixture was stirred at room temperature for a total of 48 hr with additional hydroxyamine hydrochloride (I.ISg, 17.06 mmol) and triethyiamine (1.88 g, 18.5 mmol) added portionwise. The resulting reaction mixture was concentrated and then dissolved in ethyl acetate. The organic layer was washed with saturated ammonium chloride, water.dried (sodium sulfate), concentrated to give a brown oil which solidified after standing, m. p. 184 C.
Example 6
Preparation of 1 -(2,6-Dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulfenyl-5-trimethylacetoxypyra2ole. To the solution of 1-(2,6-dichioro-4-trifiuoromethylphenyl)-3-cyano-4-trifluorcmethylsulfenyl-5-hydroxypyrazole (7.00 g, 16.6 mmol) and pyridine (4.91 g, 62.1 mmcl) in 1,2-dichicroethane at room temperature was added trimethyiacetyi chloride (4.37 g, 26.2 mmol) dropwise. Ice bath was used to maintain the temperature of the reaction. After 20 hr at room temperature, the orgainc layer was washed with five times of aqueous KHS04 tii! the aqueous solution was at pH 1. The orgainc layer was then dried (Mg S04) and concentrated to aive a solid residue. User, chromatccrachic purification via silica eel column of the soiid residue, after trituration with pentane. a off white solid (2.403 c, 23.6 % yield, 97.0 % HPLC puriety) was provided as the desired product, m. p. 82-83 C.

Example 7
Preparation of 1-(2,6-dichloro-4-trifluoromethyfphenyl)-3-cyano-4-chlorodifluoromethylsulfenyl-5-hydroxypyrazole. To the solution of 1-(2,6-dichloro-4-triilucromethylphenyl)-3-cyano-5-hydroxypyrazole (12.0 g. 37.3 mmol.) and pyridine (3.25 g, 41.0 mmol) in dichloromethane at -50- -60 C was added chiorodifluoromethanesuifenyl chloride (8.1 g, 46.6 mmol). Tr.e resulting solution was gradually warmed up to room temperature. After 20 hr, the organic layer was washed five times with water. It was then washed with brine and dried (Na2S04) to provide an oil. Upon chromatographic purification of the oil, a total of 11.6 g (26.4 mmol., 71 % yield) of the desired product with 97 % HPLC puriety was isolated. F-NMR: -30.05 ppm (CCIF2), -63.80 ppm (ArCF3).
Biological Example
The compounds 1-(2I6-dichloro-4-trifluoromethylphenyl)-3-cyanc-4-trifIuromethylthio-5-hydroxypyrazole, 1-(2,6-dichloro-4-trifluoromethylphenylr3-cyano-4-trifiuromethylsulfinyi-5-hydroxypyrazcie and 1-(2,6-dichloro-4-trifiuoromethylphenyl)-3-cyano-4-trtfluromethylsulfonyl-5-hydroxypyrazoie are formulated as a 30 mg/mL formulations in a 1:1 volume/volume solution of dimethyl sulfoxide and corn oil. Using this formulation, mixed breed dogs and cats are treated a: a rate of 10 mg of the compound per kg (mg/kg)of body weight of the dog and 20 mg/kg of the cat treated. The animals are fasted for at least 8 hours prior to -jeainent fed half cf the daiiy ration immediately prior to treatment, then allowed access to the remainder of the daiiy ration immediately following treatment.
All dogs are infested with cat fleas (Ctenocephalides feiis) and with ticks (Rhipicephaius sanguineus) 1 day prior to administration of the compound. Cats are oniy infested with fleas. The initial flea and tick counts are performed 1 day after the administration of the compounds. At 7, 14, 21 and 28 days after treatment the dogs

are re-infested with ticks and 8, 15, 22 and 29 days after treatment the dogs and cats are re-infested with fleas. At 1, 9, 16f 23 and 30 days after treatment the control of fleas and ticks in treated dogs and cats is determined versus a group of infested dogs and cats which receive a placebo consisting of a 1:1 volume/volume solution of dimethyl sulfoxide and corn oil. To determine the efficacies of the compounds, the arthropods are combea from the animals and counted. Satisfactory results are obtained for many of the above-mentioned compounds in any of the three areas of evaluation without any significant side effect for a period ranging from eight to thirty days: control of flea on dogt control of tick on dog, and control of flea on cat. They are: 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-
trifluoromethylsulfenyl-5-trimethylacetoxypyra20le 3-10 , 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifiuoromethylsulfenyl-5-ethoxypyrazole 3-1. 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-chlorodifluoromethyisulfenyl-5-hydroxypyrazole 1-9 , 1-(2?6-dichloro-4-trifIuoromethylphenyl)-3-cyano-4-trifluorornethyisulfenyl-5-hydroxypyrazoie 1-1 , 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyisulfonyl-5-hydroxypyrazole 1-5, 1-(2?6-dichloro-4-thfluoromethylphenyl)-3-cyano-4-tnfluoromethylsulfinyl-5-hydroxypyrazole 1-3 , 1-(2,6-dichioro-4-trifiuormethyi(phenyl)-3-cyano-4-trifluonmethylsulfonyl-5-N,N-dimethylcarbamyloxypyrazoie 19-1.

CLAIMS
1. A method of controlling parasites in or on an animal comprising administering to the animal a parasiticidaily effective, substantially non-emetic amount of a 1-arylpyrazoie cf formula (I):

wherein:
R20, is cyar.c, C(0)alkyl, C(S)NH2, C(NH)OR203, C(NH)SR203, alkyi, C(=NOH)NH2, C(=NNH2)NH2. C(0)NH2, C(O)NHR205, C(O)NR205R2C6l haloalkyl or heterocyclyl from the group:

optionally substituted by R^,;
R:02 is Si'C^R^., C:-C5 alkeny!, C2-C5 haioaikenyi, cycicalkyl, haiccycicalkyl.
cycioaikyi-alkyi , C2-CQ aikynyi, nitro or imidazoi-2-yi optionally substituted by alkyl,
aikcxy, ha!ca:kyi, halogen, cyano and/or nitro;
R2C3 is aikyi or haloalkyl;
R:C4 is -OH. R2Q50-, HC(0)0-, R205C(O)O-, R205OC(O)O-, NH2C(0)0-, R205NHC(O)O-,
R:osR:o6NC(0)0-, R2a£S(0)nC(0)C-, R2C6S020-, aryl-S02CK (CrC7)-oxacyc!oalkyloxy,

R2o5R206N-C(NR205)-0-, R2C5R206N-C(NH)-O-, R2C5NH.C(NR:c5)-0., R205NH-C(NH)-O-,
R2G5N=CH-0-, R205N=C(R2C6)-O-, R205NH-C(S)-O-, R2C5R206N-C(S)-O-;
R^ is alkyi, haloaikyl, cycicalkyi, halocycioaikyl, alkoxyalkyl, haloalkoxyalkyl,
adamantyl, aminoalkyt, alkyiaminoaikyi, dialkylaminoalkyl, haloalkylaminoalkyl,
di(haioalkyl)aminoalkyl, aryi optionally substituted, hetaryi optionally substituted,
aryiaikyl optionally substituted, hetarylalkyl optionally substituted, C2-C6 alkenyi, C2-
C5 alkinyl;
R206 is alky!, haloaikyl, cycioalkyl, halocycScaikyi. alkoxyalkyl, haloalkoxyalkyl, an/1
optionally substituted, hetaryi optionally substituted, arylalkyl optionally substituted,
hetarylalkyl optionally substituted;
or R205 and R2C6 may form together with the nitrogen to which they are attached a 3 to
7 membered ring which additionally may contain one or more heteroatoms selected
from nitrogen, oxygen and sulfur
X, is selected from nitrogen and C-R212;
R2,,, R212 are independently selected from halogen, hydrogen, CNT (VC3 alkyi and
N02;
R213 is selected from halogen, haloaikyl, haloaikoxy, -S(0)kCF3, and -SF5 or forms a
ring with R21A;
R214 is hydrogen or may constitute together with R213 a group of OCF20, CF2OCF2,
CF2OCF20 and CF2CF20, which forms together with the carbons they are attached
to a five to six membered ring;
and
h, k and n are independently selected from 0, 1. and 2;
and veterinariiy acceptable salts thereof.
2. A method of controiiina parasites in or on an animal as claimed in claim 1 bv administering to the animal an 1-ary!pyrazcie cf formula (II):

wherein:
R21 is cyano, C(=S)NH2, C(=NOH)NH, or C(=NNH2)NH2;
R22 's S(0)mR23;
R23 is alkyi or haloalkyi;
R24 is OH, HC(0)0-, R25C(0)0-, R25OC(0)0- or R25S(0)nC(0)0-
R25 is alkyi, haloalkyi, cycloalkyl, halocycloalkyl, alkoxyalkyl, haloalkoxyalkyl,
adamantyl, adamantyl, aminoalkyl, alkyiaminoalkyi, dialkylaminoalkyl,
haloalkylaminoalkyl, di(haloaIkyi)aminoalkyl, aryi optionally substituted, hetaryl
optionally substituted, arylalkyl optionally substituted, hetarylalkyl optionally
substituted, C2-Cs alksnyi, C2-C6 alkinyl,
or two groups R25 may form together with the nitrogen to which they are attached a 3
to 7 membered ring which additionally may contain one or more heteroatoms
selected from nitrogen, oxygen and sulfur;
X is selected from nitrogen and C-R32;
R31 and R32 are independently selected from halogen, hydrogen, CN, CrC3 alkyi and
N02;
R33 is selected from haicgen, haloalkyi, haloalkcxy, -S(0)rCF3, and -SF5 or forms a
ring together with R^ ;
R^ is hydrogen or may constitute together with R213 a group of OCF20, CF2OCF2,
CF2OCF20 and CF2CF20, which forms together with the carbons they are attached
to a five to six membered ring;
m is 0, 1 or 2;
r is selected from 0, 1, and 2;

and veterinarily acceptable salts thereof; provided that if R:1 is cyano then R24 is not R25R25-N-C(0)-O.
3. A compound of formula (II) or salt there of as hereinbefore described in claim 2 with the proviso that the compound is not 1-(2,6-dichioro-4-trifluorcmethylphenyl)-3-cyano-4-trifluoromethylthio-5-hydroxypyrazole.
4. A compound according to claim 3 wherein R21 is cyano;
Re is S(0)mR23;
R23 is haloalkyi, preferably CF3;
R24isOH;
X is selected from nitrogen and C-R3:;
R31 and R32 are independently selected from halogen,
R33 is selected from halogen, haloalkyi, hsioaikoxy, -S(0)fCF3, and -SF5;
m and r are independently selected from 0, 1, and 2.
5. The compound of formula (!) as defined in Claim 1 or the compound of formula (II) as defined in any one of ciaims 2,3 or 4 which is 1-(2f6-dichloro-4-trifIuoromethylphenyl)-3-cyano-4-trifturomethyisulfinyi-5-hydroxypyrazole.
6. The compound of formula (I) as defined in Claim 1 or the compound of formula (II) as defined in any one of ciaims 2,3 or 4 which is 1-(2,6-dichloro-4-trifIuoromethylphenyl)-3-cyano-4-trifIurcmethylsulfonyl-5-hydroxypyrazole.
7. A composition comprising a parasiticida!!y effective, amount of a compound of formula (I) or (II) or a salt thereof as defined ;n any one of the foregoing ciaims and an acceptable carrier.

8. A composition comprising a parasiticidally effective, amount of a compound of formula (II) or a salt thereof and an acceptable carrier as defined in any one of ciaims 2, 3,4, 5 or 6.
9. The method according to claims 1 wherein the animal is a domestic animal.
10. The method according to claim 1 wherein the 1-aryipyrazoie is administered orally in a dose to the animai in a dose range from 0.1 to 500 mg/kg.
11. A compound of formula (I) according to claim 1 wherein
R201 is cyano, C(0)alkyl, C(S)NH2, C(NH)OR203, C(NH)SR2C3, alkylT C(=NOH)NH2, C(=NNH2)NH2, C(0)NH2, C(O)NHR205; C(O)NR205R2C6, haicaikyi or heterocyclyl from the group:

optionally substituted by R203;
and/or
R202 is S(O)hR203, C2-C6 aikenyl, C2-C6 haloalkenyl, cyclcalkyl, halocycloalkyl,
cycioalkyl-alkyl, C2-C6 alkynyl, nitro or imidazol-2-yl opticraily substituted by alkyl,
aikoxy, haioalkyl, halogen, cyano and/or nitro;
and/or
R:c, is -OH, R2G50-, HC(0)0-, R205C(O)O-, R205OC(O)O-, NH2C(0)0-. R:o5NKC(0)0~,
^205^206^^(0)0-, R2csS(0)nC(0)0-, R206SO2O-P aryl-SG-C-, (0,-C7)-oxacycicaiky!oxy,
Rzo5R2o6N-C(NR205)-0-1 R2a5R2c6N-C(NH)-0- , R2C£NH-C(NR2C5;-0-, R2C5NH-C(NH)-0-,
R205N=CH-O-, R20SN=C(R2D6)-O-1 R2C5MH-C(S)-0^, R^c-R^N-C^O- ;

and/or
R:14 constitutes together with R213 a group of OCF20, CF2OCF2l CF2OCF20 and CF2CF20, which forms together with the carbons they are attached to a five to six membered ring;
12. The use of a compound of formula (i) according to claim 1 for controlling parasites in animals.

13. A method of controlling parasites in or on an animal substantially as
lierein described and exemplified.
14. A composition substantially as herein described and exemplified.

Documents:

in-pct-2002-0809-che abstract-duplicate.pdf

in-pct-2002-0809-che claims-duplicate.pdf

in-pct-2002-0809-che description (complete)-duplicate.pdf

in-pct-2002-809-che power of attorney.pdf

in-pct-2002-809-che claims.pdf

in-pct-2002-809-che form 1.pdf

in-pct-2002-809-che form 2.pdf

in-pct-2002-809-che form 6.pdf

in-pct-2002-809-che power of attorney.pdf

in-pct-2002-809-che-assignment.pdf

in-pct-2002-809-che-claims.pdf

in-pct-2002-809-che-correspondance others.pdf

in-pct-2002-809-che-correspondance po.pdf

in-pct-2002-809-che-description complete.pdf

in-pct-2002-809-che-form 1.pdf

in-pct-2002-809-che-form 19.pdf

in-pct-2002-809-che-form 26.pdf

in-pct-2002-809-che-form 3.pdf

in-pct-2002-809-che-form 5.pdf

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Patent Number

224612

Indian Patent Application Number

IN/PCT/2002/809/CHE

PG Journal Number

49/2008

Publication Date

05-Dec-2008

Grant Date

21-Oct-2008

Date of Filing

30-May-2002

Name of Patentee

MERIAL LIMITED

Applicant Address

3239 SATELLITE BOULEVARD, BUILDING 500, DULUTH, GA 30096,

Inventors:

#	Inventor's Name	Inventor's Address
1	SCHNATTERER, STEFAN	SCHILLERRING 10, 65795 HATTERSHEIM,
2	BASTIAANS, HENRICUS, MARIA, MARTINUS	STOCKHEIMER WEG 9A, 61250 USINGEN,
3	HUBER, SCOT, KEVIN	6104 BRAMBLE-WOOD DRIVE, RALEIGH, NC 27612,
4	CHOU, DAVID TEH-WEI	5120 RICHLAND DRIVE, RALEIGH, NC 27612,

PCT International Classification Number

C07D231/28

PCT International Application Number

PCT/EP00/12100

PCT International Filing date

2000-12-01

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	60/168,658	1999-12-02	U.S.A.