Patent EA-004144-B1 (EA)
Title: Method of controlling parasites in animals
Inventor: RIBEILL YVES
IPC: A61P33/00
Filed: 1999-12-10
Abstract: 1. A method of controlling parasites in an animal comprising administering orally to the animal a parasiticidally effective, substantially non-emetic amount of a 1-arylpyrazole of formula (I): wherein: R1 is cyano, acetyl, C(S)NH2, C((NOH)NH2 or C((NH2)NH2; R2 is S(O)nR3; C2-C3 alkenyl, C2-C3 haloalkenyl, cycloalkyl, halocycloalkyl or C2-C3 alkynyl; R3 is alkyl or trifluoromethyl; R4 is -N=C(R5)-Z-R6, -N=C(R5)-N(R7)-R8, or -N(R9)-C(R5)=NR6; R5 is hydrogen; alkyl; or alkyl substituted by halogen, alkoxy, haloalkoxy or -S(O)mR15; R6 and R7 each independently represent hydrogen, alkyl, C3-C5 alkenyl or C3-C5 alkynyl; or alkyl substituted by one or more halogen, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, cyano or -S(O)mR15 or alkyl substituted by phenyl or pyridyl each of which is optionally substituted with one or more groups selected from halogen, nitro and alkyl; or R6and R7 may form together with the nitrogen to which they are attached a 3 to 7 membered ring which may additionally contain one or more heteroatoms selected from oxygen, nitrogen or sulfur; R8 is alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, R14CO- or -S(O)tR10; R9, R10 and R14 are alkyl or haloalkyl; R11 and R12 are independently selected from halogen, hydrogen, CN and NO2; R13 is selected from halogen, haloalkyl, haloalkoxy, -S(O)qCF3, and -SF5; R15 is alkyl or haloalkyl; X is selected from nitrogen and C-R12; Z is O, S(O)a; or NR7; a, m, n and q are independently selected from 0, 1, and 2; and t is 0 or 2; and veterinarily acceptable salts thereof. 2. The method according to Claim 1 wherein the compound of formula (I) is that wherein: R1 is cyano; R2 is S(O)n R3; R3 is alkyl or haloalkyl; R4 is -N=C(R5)-Z-R6; R5 is hydrogen, alkyl or haloalkyl; Z is O, S(O)a; or NR7; R6 and R7 are independently selected from hydrogen and unsubstituted or substituted alkyl; or R6 and R7 may form together with the nitrogen to which they are attached a 3 to 7 membered ring which may additionally contain one or more heteroatoms selected from oxygen, nitrogen or sulfur; X is selected from nitrogen and C-R12; R11 and R12 are independently selected from halogen, hydrogen, CN and NO2; R13 is selected from halogen, haloalkyl, haloalkoxy, -S(O)qCF3, and -SF5; a, n and q are independently selected from 0, 1, and 2. 3. A compound of formula (II): wherein: R21 is cyano, alkyl, haloalkyl, acetyl or -C(=S)NH2, C(=NOH)NH2 or C(=NNH2)NH2; R22 is S(O)mR23; R23 is alkyl or haloalkyl; R24 is -N=C(R25)N(R26)(R27) or -N=C(R25)-N(R27)-R28; R25 is hydrogen or alkyl; or alkyl substituted by one or more halogen, alkoxy, haloalkoxy or -S(O)mR35; R26 and R27 each independently represent hydrogen, alkyl, alkenyl or alkynyl; or alkyl substituted by one or more halogen, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, cyano or -S(O)mR35; or alkyl substituted by phenyl or pyridyl which rings are optionally substituted with one or more groups selected from halogen, nitro and alkyl; wherein R35 is alkyl or haloalkyl and m is zero, one or two; X is selected from nitrogen and C-R32; R28 is alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or -S(O)tR30; R30 is alkyl or haloalkyl; R31 and R32 are independently selected from halogen, hydrogen, CN and NO2; R33 is selected from halogen, haloalkyl, haloalkoxy, -S(O)rCF3, and -SF5; m and r are independently selected from 0, 1, and 2; and t is 0 or 2; with the exclusion of the compound wherein: R21 is cyano; R22 is SCF2CH3; R25 is hydrogen; X is C-R32; R26 and R27 are methyl; R31 and R32 are chlorine; and R33 is trifluoromethyl; and veterinarily acceptable salts thereof. 4. A method of controlling parasites in or on an animal comprising administering orally to the animal a parasiticidally effective, substantially non-emetic amount of a 1-arylpyrazole of formula (XX): wherein: R201 is cyano, C(O)alkyl, C(S)NH2, alkyl, C(=NOH)NH2 or C(=NNH2)NH2; R202 is S(O)hR203, C2-C3 alkenyl, C2-C3 haloalkenyl, cycloalkyl, halocycloalkyl or C2-C3 alkynyl; R203 is alkyl or trifluoromethyl; R204 is -N(R205)C(O)CR206R207R208-N(R205)C(O) aryl, N(R205)C(O)OR207; R205 is alkyl, haloalkyl, cycloalkyl, halocycloalkyl, cycloalkylalkyl, halocycloalkylalkyl, alkoxyalkyl, haloalkoxyalkyl, C3-C5 alkenyl, C3-C5 alkynyl, C3-C5 haloalkenyl or C3-C5 alkynyl, R206 is hydrogen, halogen, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, formyloxy, alkylcarbonyloxy, haloalkylcarbonyloxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, dialkylamino, haloalkylamino, di(haloalkyl)amino, cycloalkyloxy, halocycloalkyloxy, alkoxyalkoxy, haloalkoxyalkoxy, alkoxyalkoxyalkoxy, aryloxy, or arylalkoxy; R207 and R208 are independently hydrogen, alkyl, haloalkyl, cycloalkyl, or halocycloalkyl; or R207 and R208 may form together with the carbon 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; X1 is selected from nitrogen and C-R212; R211 and R212 are independently selected from halogen, hydrogen, CN and NO2; R213 is selected from halogen, haloalkyl, haloalkoxy, -S(O)kCF3, and -SF5; and h and k are independently selected from 0, 1, and 2; and veterinarily acceptable salts thereof. 5. The method according to Claim 4, wherein: R201 is cyano; R202 is S(O)hR203; R203 is alkyl or trifluoromethyl; R204 is -N(R205)C(O)CR206R207R208; R205 is alkyl, halogenalkyl, cycloalkyl, cycloalkylalkyl; R206 is hydrogen, alkoxy, haloalkoxy; R207 and R208 are independently hydrogen, alkyl, haloalkyl, cycloalkyl, or halocycloalkyl; or R207 and R208 may form together with the carbon 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; X1 is selected from nitrogen and C-R212; R211 and R212 are independently selected from halogen, hydrogen, CN and NO2; R213 is selected from halogen, haloalkyl, haloalkoxy, -S(O)kCF3, and -SF5; and h and k are independently selected from 0, 1, and 2. 6. A compound of formula (XX) wherein: R201 is cyano, C(O) alkyl, alkyl, C(S)NH2, C((NOH)NH2 or C((NNH2)NH2; R202 is S(O)hR203, C2-C3 alkenyl, C2-C3 haloalkenyl, C2-C3, cycloalkyl, halocycloalkyl, cycloalkylalkyl or C2-C3 haloalkyl; R203 is alkyl or trifluoromethyl; R205 is alkyl, haloalkyl, cycloalkyl, halocycloalkyl, cycloalkylalkyl, halocycloalkylalkyl, alkoxyalkyl, haloalkoxyalkyl, C3-C5 alkenyl, C3-C5 alkynyl, C3-C5 haloalkenyl or C3-C5 alkynyl, R206 is hydrogen, halogen, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, formyloxy, alkylcarbonyloxy, haloalkylcarbonyloxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, dialkylamino, haloalkylamino, di(haloalkyl)amino, cycloalkyloxy, halocycloalkyloxy, alkoxyalkoxy, haloalkoxyalkoxy, alkoxyalkoxyalkoxy, aryloxy, or arylalkoxy; R207 and R208 are independently hydrogen, alkyl, haloalkyl, cycloalkyl, or halocycloalkyl; or R207 and R208 may form together with the carbon 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; X1 is selected from nitrogen and C-R212; R211 and R212 are independently selected from halogen, hydrogen, CN and NO2; R213 is selected from halogen, haloalkyl, haloalkoxy, -S(O)kCF3, and -SF5; and h and k are independently selected from 0, 1, and 2; and veterinarily acceptable salts thereof, provided, that it is not 3-cyano-1-(2,6-dichloro-4-4-trifluoromethylphenyl)-5-(N-ethoxycarbonyl-N-methyl) amino-4-triflouromethylthiopyrazole. 7. A method according to any one of Claims 1, 2, 4 or 5 wherein the animal is a domestic animal, preferably a dog or a cat. 8. The method according to any one of Claims 1, 2, 4, 5 or 7 wherein the 1-arylpyrazole is administered orally to the animal in a dose range generally from 0.1 to 500 mg/kg. 9. The method according to any one of Claims 1, 2, 3, 4, 5, 7 or 8 wherein the 1-arylpyrazole is administered in a frequency of treatment from about once per week to about once per year.