WO2013092942A1 - Use of aminobenzamide derivatives for controlling animal parasites - Google Patents

Use of aminobenzamide derivatives for controlling animal parasites Download PDF

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WO2013092942A1
WO2013092942A1 PCT/EP2012/076538 EP2012076538W WO2013092942A1 WO 2013092942 A1 WO2013092942 A1 WO 2013092942A1 EP 2012076538 W EP2012076538 W EP 2012076538W WO 2013092942 A1 WO2013092942 A1 WO 2013092942A1
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phenyl
methyl
chloro
formula
compounds
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PCT/EP2012/076538
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French (fr)
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Peter Maienfisch
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Syngenta Participations Ag
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4192—1,2,3-Triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A01N37/22—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof the nitrogen atom being directly attached to an aromatic ring system, e.g. anilides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/34—Nitriles
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
    • A—HUMAN NECESSITIES
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides

Definitions

  • the invention relates to a composition comprising at least one aminobenzamide derivatives or a salt thereof for controlling animal parasites, veterinary pharmaceutical compositions comprising at least one aminobenzamide derivatives or a salt thereof for preventing infection with diseases transmitted through parasites, its use for the preparation of a veterinary pharmaceutical for controlling animal parasites, and a method for preventing infection with diseases transmitted through parasites.
  • the compounds of the present invention are also usfull for medical uses.
  • the infestation of animals, domestic animals, companion animals and agricultural livestock alike, with parasites represents a problem.
  • the infested animals are infected with diseases transmitted through parasites, like e.g. lyme disease, a variety of sometimes fatal viral diseases or the immune system of the animals becomes weak due to the infestation, so that the animals become prone to other diseases, like e.g. bacterial infections.
  • diseases transmitted through parasites like e.g. lyme disease
  • a variety of sometimes fatal viral diseases or the immune system of the animals becomes weak due to the infestation, so that the animals become prone to other diseases, like e.g. bacterial infections.
  • costly medicaments have to be administered, and, if the treated animals are agricultural livestock then the food safety is jeopardized.
  • the infestation of agricultural livestock with parasites is very often accompanied with a decrease in performance in terms of quality and quantity of produced meat, milk, egg, wool, or fur.
  • blood-sucking ectoparasites and ectoparasites causing myiasis are potential transmitters of a broad variety of pathogens besides all other secondary effects of the ectoparasitic infestation as there are blood-loss, irritation, inflammation, secondary bacterial infection, secondary parasiticidal infection (e.g. myiasis) and direct toxicosis (tick paralysis).
  • myiasis secondary parasiticidal infection
  • direct toxicosis titanium paralysis
  • the invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising at least one compound of formula (I)
  • a 1 , A 2 and A 3 are independently of one another C-X, N-X, nitrogen, oxygen or sulfur,
  • each X is independently hydrogen, halogen, Ci-C 4 alkyl or trifluoromethyl
  • R 1 and R 2 are independently of one another hydrogen, Ci-C 4 alkyl or Ci-C 4 alkylcarbonyl; G' and G 2 are independently of one another oxygen or sulfur;
  • Q 1 is aryl or aryl substituted by one to five substituents R 3 , which may be the same or different, or Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 3 , which may be the same or different;
  • each R 3 is independently cyano, nitro, hydroxy, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 2 - C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halo- cycloalkyl, Ci-C 3 alkoxy, Ci-Cshaloalkoxy, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkyl- sulfmyl, Ci-C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl, Ci-C 3 haloalkylsulfonyl, Ci-C 4 alkyl- amino, di-(Ci-C 4 alkyl)amino, Ci-C 4
  • Q 2 is a moiety of formula (II) or (III)
  • Y 1 and Y 5 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci- C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, Ci-C 3 haloalkylsulfinyl, Ci-C 3 alkyl- sulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 3 is C 2 -C 6 perfiuoroalkyl, Ci-C 6 perfluoroalkylthio, Ci-C 6 perfluoroalkylsulfinyl or Ci-C 6 per- fluoroalkylsulfonyl;
  • Y 2 and Y 4 are independently of each other hydrogen, halogen or Ci-C 4 alkyl;
  • Y 6 and Y 9 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci- C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfmyl, Ci-C 3 haloalkylsulfmyl, Ci-C 3 alkyl- sulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 8 is Ci-C 4 haloalkoxy, C 2 -C 6 perfiuoroalkyl, Ci-C 6 perfluoroalkylthio, Ci-C 6 perfluoroalkyl- sulfmyl or Ci-Ceperfluoroalkylsulfonyl;
  • Y 7 is hydrogen, halogen or Ci-C 4 alkyl
  • Preferred values of A 1 , A 2 , A 3 , X, R 1 , R 2 , G 1 , G 2 , Q 1 , Q 2 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are, in any combination, as set out below.
  • a 1 , A 2 and A 3 are C-X and one is sulfur, more preferably A 1 and A 3 are C-X and A 2 is sulfur.
  • each X is independently hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl, more preferably hydrogen, fluoro, chloro, bromo or methyl, even more preferably hydrogen, chloro, bromo or methyl, most preferably hydrogen.
  • R 1 is hydrogen, methyl, ethyl or acetyl, most preferably hydrogen.
  • R 2 is hydrogen, methyl, ethyl or acetyl, most preferably hydrogen.
  • G 1 is oxygen
  • G 2 is oxygen.
  • Q 1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, nitro or phenyl.
  • Q 1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Even more preferably Q 1 is phenyl or pyridyl substituted by one to three substituents independently selected from cyano, fluoro, chloro or methyl.
  • Especially preferred groups for Q 1 are 5- bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro- phenyl, l,3-dimethyl-pyrazol-5-yl, 2-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2- fluoro-3-trifluoromethyl-phenyl, furan-2-yl, 2-methyl-phenyl, 3-methyl-pyrid-2-yl,
  • Q 1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 2-chloro-phenyl, 3-chloro- phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2- yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro- phenyl, l,3-dimethyl-pyrazol-5-yl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2-f uoro-3-trifluoro- methyl-phenyl, furan-2-yl, 2-methyl-phenyl, 3-methyl-pyrid-2-yl, 4-methylthi
  • a particularly preferred group of compounds are compounds of formula (I) wherein Q 1 is aryl or aryl substituted by one to five substituents R 3 , which may be the same or different.
  • Q 1 is phenyl or phenyl substituted by one to three substituents
  • Q 1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Even more preferably Q 1 is phenyl substituted by one to three substituents independently selected from cyano, fluoro, chloro or methyl.
  • Especially preferred groups for Q 1 are 2-bromo-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano- phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 2-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro- 3 -trifluoromethyl -phenyl, 2-methyl-phenyl, 4-methylthio-phenyl, 4-nitro-phenyl, phenyl, 2- trifluoromethyl-phenyl and 4-trifluoromethyl-phenyl.
  • Q 1 Most especially preferred groups for Q 1 are 2-bromo-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano-phenyl, 2,5-dichloro- phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3-trifluoromethyl-phenyl, 2-methyl- phenyl, 4-methylthio-phenyl, 4-nitro-phenyl and phenyl.
  • Another particularly preferred group of compounds are compounds of formula (I) wherein Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 3 , which may be the same or different.
  • the heterocyclyl group is preferably a heteroaryl group.
  • Q 1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, nitro or phenyl.
  • Q 1 is pyridyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Even more preferably Q 1 is pyridyl substituted by one to three substituents independently selected from cyano, fluoro, chloro or methyl.
  • Especially preferred groups for Q 1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2-chloro- pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5- trifluoromethyl-pyrid-2-yl, l,3-dimethyl-pyrazol-5-yl, 2-fluoro-pyrid-3-yl, furan-2-yl, 3- methyl-pyrid-2-yl, 2-methylthio-pyrid-3-yl, pyrid-3-yl and pyrid-4-yl.
  • More especially preferred groups for Q 1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2-chloro-pyrid-3-yl, 2- chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3 -chloro-5 -trifluoromethyl - pyrid-2-yl, 3 -dimethyl -pyrazol-5-yl, 2-fluoro-pyrid-3-yl, furan-2-yl, 3-methyl-pyrid-2-yl and pyrid-3-yl.
  • Q 1 are 5-bromo-pyrid-3-yl, 2-chloro-pyrid- 3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 2- fluoro-pyrid-3-yl, 3-methyl-pyrid-2-yl and pyrid-3-yl.
  • Q 2 is a moiety of formula (II).
  • Especially preferred groups for Q 2 are 4- heptafluoroisopropyl-2,6-dimethyl-phenyl and 4-heptafluoroisopropyl-2,6-diethyl-phenyl.
  • Y 1 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
  • Y 2 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen.
  • Y 3 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfmyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
  • heptafluoroprop-2-ylsulfinyl heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl, most preferably heptafluoroprop-2-yl.
  • Y 4 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen.
  • Y 5 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
  • Y 6 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
  • Y 7 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen.
  • Y 8 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfmyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
  • heptafluoroprop-2-ylsulfinyl heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl, most preferably heptafluoroprop-2-yl.
  • Y 9 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
  • a particularly preferred group of compounds of the embodiment (A) are compounds of formula (la)
  • R , R G , G Q 1 and Q z are as defined in relation to formula (I) and X and X are independently defined as X in relation to formula (I); or salts or N-oxides thereof.
  • the preferences for R 1 , R 2 , G 1 , G 2 , Q 1 , Q 2 , X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • a group of most particularly preferred compounds are compounds of formula (la) wherein X 1 and X 2 are both hydrogen.
  • Another group of particularly preferred compounds are compounds of formula (lb)
  • R , R G , G z , Q 1 and Q z are as defined in relation to formula (I) and X and X are independently defined as X in relation to formula (I); or salts or N-oxides thereof.
  • the preferences for R 1 , R 2 , G 1 , G 2 , Q 1 , Q 2 , X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • a group of most particularly preferred compounds are compounds of formula (lb) wherein X 1 and X 2 are both hydrogen.
  • a further group of most particularly preferred compounds are compounds of formula (lb) wherein X 1 is bromo and X 2 is hydrogen.
  • a further group of particularly preferred compounds od the embodiment (A) are compounds of formula (Ic)
  • R , R G , G Q 1 and Q z are as defined in relation to formula (I) and X and X are independently defined as X in relation to formula (I); or salts or N-oxides thereof.
  • the preferences for R 1 , R 2 , G 1 , G 2 , Q 1 , Q 2 , X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • a group of most particularly preferred compounds are compounds of formula (Ic) wherein X 1 and X 2 are both hydrogen.
  • a further group of most particularly preferred compounds are compounds of formula (Ic) wherein X 1 is hydrogen and X 2 is chloro. Yet a further group of most particularly preferred compounds are compounds of formula (Ic) wherein X 1 is hydrogen and X 2 is bromo. Another group of most particularly preferred compounds are compounds of formula (Ic) wherein X 1 is hydrogen and X 2 is methyl.
  • One embodiment of the embodiment (A) the present invention provides a compound of formula (Ix)
  • a 1 , A 2 and A 3 are independently of one another carbon, nitrogen, nitrogen oxide, oxygen or sulfur with the proviso that at least one of A 1 , A 2 or A 3 is not carbon and no more than one of A 1 , A 2 or A 3 is oxygen or sulfur;
  • R 1 and R 2 are independently of one another hydrogen, Ci-C 4 alkyl or Ci-C 4 alkylcarbonyl;
  • G 1 and G 2 are independently of one another oxygen or sulfur
  • X are independently of one another halogen, Ci-C 3 alkyl or trifluoromethyl
  • n 0, 1 , 2 or 3;
  • Q 1 is aryl or aryl substituted by one to five substituents independently selected from R 3 , or heterocyclyl or heterocyclyl substituted by one to five substituents independently selected from R 3 ;
  • R 3 are independently of one another cyano, nitro, hydroxy, halogen, Ci-C 4 alkyl, Ci-C 4 halo- alkyl, C 2 -C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 6 cycloalkyl, C3-Cehalocycloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci- C 3 alkylsulfinyl, Ci-C 3 haloalkylsulfmyl, Ci-C 3 alkylsulfonyl, Ci-C 3 haloalkylsulfonyl, Ci- C 4 alkylamino, di-(Ci-C 4 alkyl)amino, Ci-C 4 alkylcarbon
  • Q 2 is a moiety of formula (II) or (III)
  • Y 1 and Y 5 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci- C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, Ci-C 3 haloalkylsulfinyl, Ci-C 3 alkyl- sulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 3 is C 2 -C 6 perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C 6 perfluoroalkylsulfinyl or Ci-C 6 per- fluoroalkylsulfonyl;
  • Y 2 and Y 4 are independently of each other hydrogen, halogen or Ci-C 4 alkyl;
  • Y 6 and Y 9 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, d- C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, Ci-C 3 haloalkylsulfinyl, Ci-C 3 alkyl- sulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 8 is Ci-C 4 haloalkoxy, C 2 -C 6 perfluoroalkyl, Ci-C 6 perfluoroalkylthio, Ci-C 6 perfluoroalkyl- sulfinyl or Ci-C 6 perfluoroalkylsulfonyl;
  • Y 7 is hydrogen, halogen or Ci-C 4 alkyl
  • a 1 , A 2 and A 3 are carbon and one is sulfur, most preferably A 1 and
  • a 3 are carbon and A 2 is sulfur.
  • X is fluoro, chloro, methyl or trifluoromethyl, most preferably fluoro, chloro or methyl.
  • n is 0, 1 or 2, even more preferably 0 or 1 , most preferably 0.
  • R 1 , R 2 , G 1 , G 2 , Q 1 , Q 2 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • Table 1 provides 29 compounds of formula (la') wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropy 1-pheny 1.
  • Table 2 provides 29 compounds of formula (lb') wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 3 provides 29 compounds of formula (Ic') wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 4 provides 29 compounds of formula (lb") wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 5 provides 29 compounds of formula (Ic") wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 6 provides 29 compounds of formula (Ic'") wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 7 provides 29 compounds of formula (Ic"") wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • the invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising at least one compound of formula (I
  • a , A , A and A are independently of one another C-X-R , C-R or nitrogen, provided that
  • R 1 and R 2 are independently of one another hydrogen, Ci-C 4 alkyl or Ci-C 4 alkylcarbonyl;
  • G 1 and G 2 are independently of one another oxygen or sulfur
  • each R 3 is independently hydrogen, Ci-Ci 2 alkyl, Ci-Ci 2 haloalkyl, C 2 -Csalkenyl, C 2 -
  • each X is independently oxygen, sulfur or N-R 4 ;
  • each R 4 is independently hydrogen, Ci-C 4 alkyl or Ci-C 4 alkylcarbonyl;
  • each R 5 is independently hydrogen, halogen, Ci-C 4 alkyl or trifluoromethyl
  • Q 1 is aryl or aryl substituted by one to five substituents R 6 , which may be the same or different, or Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 6 , which may be the same or different; wherein each R 6 is independently cyano, nitro, hydroxy, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 2 - C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C3-C 6 cycloalkyl, C 3 - C 6 halocycloalkyl, Ci-C 3 alkoxy, Ci-C 3 haloalkoxy, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci- C 3 alkylsulfinyl, Ci-C 3 haloalkylsulfin
  • Q 2 is a moiety of formula (II) or (III)
  • Y ! and Y 5 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci- C 4 alkoxy-Ci-C 4 -alkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, d- C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 3 is C 2 -C 6 perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C 6 perfluoroalkylsulfinyl or Ci-C 6 per- fluoroalkylsulfonyl;
  • Y 2 and Y 4 are independently of each other hydrogen, halogen or Ci-C 4 alkyl;
  • Y 6 and Y 9 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci- C 4 alkoxy-Ci-C 4 -alkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, d- C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 8 is Ci-C 4 haloalkoxy, C 2 -C 6 perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C 6 perfluoroalkyl- sulfinyl or Ci-Ceperfluoroalkylsulfonyl;
  • Y 7 is hydrogen, halogen or Ci-C 4 alkyl
  • Preferred values of A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , R 3 , X, R 4 , R 5 , Q 1 , R 6 , Q 2 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are, in any combination, as set out below.
  • a 1 is C-X-R 3 or C-R 5 .
  • a 2 is C-X-R 3 or C-R 5 .
  • a 3 is C-X-R 3 or C-R 5 .
  • a 4 is C-X-R 3 or C-R 5 .
  • a 1 , A 2 , A 3 and A 4 are C-X-R 3 .
  • a 1 , A 2 , A 3 and A 4 are C-X-R 3 .
  • a 1 , A 2 , A 3 and A 4 is C-X-R 3 .
  • R 1 is hydrogen, methyl, ethyl or acetyl.
  • R 1 is hydrogen, methyl or ethyl.
  • R 1 is hydrogen or ethyl.
  • R 1 is hydrogen
  • R 2 is hydrogen, methyl, ethyl or acetyl.
  • R 2 is hydrogen, methyl or ethyl.
  • R 2 is hydrogen or ethyl.
  • R 2 is hydrogen
  • G 1 is oxygen
  • G 2 is oxygen
  • each R 3 is independently hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 2 - C 4 alkenyl, C 2 -C 4 alkynyl, phenyl or phenyl substituted by one to three substituents independently selected from halogen or Ci-C 4 alkyl.
  • each R 3 is independently hydrogen, methyl, ethyl, n-propyl, allyl, phenyl or phenyl mono-substituted by halogen or methyl.
  • each R 3 is independently hydrogen, methyl or ethyl.
  • each R 3 is independently hydrogen or methyl.
  • each X is independently oxygen or sulfur.
  • each X is oxygen.
  • each R 4 is independently hydrogen or methyl.
  • each R 5 is independently hydrogen, fluoro, methyl or trifluoromethyl. More preferably each R 5 is independently hydrogen or fluoro.
  • each R 5 is hydrogen.
  • Q 1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of such groups for Q 1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3- yl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro- pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5-trifluoromethyl-pyrid-2- yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 1 ,3 -dimethyl -pyrazol-5-yl, 4- fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2-fluoro-3-trifluoromethyl-phenyl, 2-methyl-phenyl, 3- methyl-pyrid-2-y
  • Q 1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of such preferred groups for Q 1 are 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro- pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-pyrid-3- yl, 2-fluoro-3 -trifluoromethyl -phenyl, 2-methyl-phenyl, 3-methyl-pyrid-2-yl, 2-methylthio- pyrid-3 -yl and phenyl.
  • Q 1 is phenyl substituted by one substituent selected from cyano, fluoro or chloro.
  • substituents selected from cyano, fluoro or chloro.
  • Examples of even more preferred groups for Q 1 are 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano-phenyl and 4-fluoro-phenyl.
  • Q 1 is 4-fluoro-phenyl.
  • Each R 6 is independently cyano, nitro, hydroxy, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl,
  • a particularly preferred group of compounds are compounds of formula (I) wherein Q 1 is aryl or aryl substituted by one to five substituents R 6 , which may be the same or different.
  • Q 1 is phenyl or phenyl substituted by one to three substituents
  • Q 1 independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • groups for Q 1 are 2-bromo-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3- chloro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2- fluoro-3-trifluoromethyl-phenyl, 2-methyl-phenyl, 4-nitro-phenyl and phenyl.
  • Q 1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Examples of such preferred groups for Q 1 are 2-chloro-phenyl, 3-chloro-phenyl
  • Another particularly preferred group of compounds are compounds of formula (I) wherein Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 6 , which may be the same or different.
  • the heterocyclyl group is preferably a heteroaryl group.
  • Q 1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Examples of such groups for Q 1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2-chloro-pyrid- 3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5- trifluoromethyl-pyrid-2-yl, l,3-dimethyl-pyrazol-5-yl, 2-fluoro-pyrid-3-yl, 3-methyl-pyrid-2- yl, 2-methylthio-pyrid-3-yl, l,2,3-thiadiazol-4-yl and thiophen-2-yl.
  • Q 1 is pyridyl or pyridyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Examples of such preferred groups for Q 1 are 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid- 3-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 2-fluoro-pyrid-3-yl, 3-methyl-pyrid-2-yl and 2- methylthio-pyrid-3 -yl.
  • Q 2 is a moiety of formula (II).
  • Especially preferred groups for Q 2 are 4- heptafluoroisopropyl-2,6-dimethyl-phenyl, 4-heptafluoroisopropyl-2,6-diethyl-phenyl and 4- heptafluoroisopropyl -2 -methoxymethyl-6-methyl -phenyl.
  • Y 1 is cyano, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl.
  • Y 1 is cyano, chloro, methyl or trifluoromethyl.
  • Y 1 is methyl or ethyl.
  • Y 1 is methyl
  • Y 2 is hydrogen, fluoro, chloro or methyl.
  • Y 2 is hydrogen
  • Y 3 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
  • Y 3 is heptafiuoroprop-2-yl.
  • Y 4 is hydrogen, fluoro, chloro or methyl.
  • Y 4 is hydrogen
  • Y 5 is cyano, chloro, methyl, ethyl or trifluoromethyl.
  • Y 5 is cyano, chloro, methyl or trifluoromethyl.
  • Y 5 is methyl or ethyl.
  • Y 5 is methyl
  • Y 6 is cyano, chloro, methyl, ethyl or trifluoromethyl.
  • Y 6 is methyl or ethyl.
  • Y 6 is methyl
  • Y 7 is hydrogen, fluoro, chloro or methyl.
  • Y 7 is hydrogen
  • Y 8 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
  • Y 8 is heptafluoroprop-2-yl.
  • Y 9 is cyano, chloro, methyl, ethyl or trifluoromethyl.
  • Y 9 is methyl or ethyl.
  • Y 9 is methyl
  • Y 1 and Y 5 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkylthio, Ci-Cshaloalkylthio, Ci-C 3 alkylsulfinyl, Ci-Cshaloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl.
  • Y 6 and Y 9 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, Ci-C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl.
  • the invention provides a novel compound of formula (la)
  • a 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , Q 1 , Y 1 , Y 2 , Y 3 , Y 4 and Y 5 are as defined in relation to
  • a 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , Q 1 , Y 6 , Y 7 , Y 8 and Y 9 are as defined in relation to
  • Q 1 and Q 2 z are as defined in relation to formula I, and each X is independently oxygen or sulfur; or salts or N-oxides thereof.
  • the preferences for A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , Q 1 and Q 2 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • the invention provides a novel compound of formula (Ic) wherein A 1 , Q1 1 and Q 2 z are as defined in relation to formula I, and each X is oxygen; or salts or N-oxides thereof.
  • the preferences for A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , Q 1 and Q 2 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • a group of particularly preferred compounds are compounds of formula (Ic) wherein X 1 , X 3 and X 4 are hydrogen and X 2 is hydroxy.
  • a further group of particularly preferred compounds are compounds of formula (Ic) wherein X 1 , X 2 and X 3 are hydrogen and X 4 is hydroxy.
  • Another group of particularly preferred compounds are compounds of formula (Ic) wherein X 1 , X 2 and X 3 are hydrogen and X 4 is allyloxy.
  • a further group of particularly preferred compounds are compounds of formula (Ic) wherein X 1 and X 3 are both hydrogen and X 2 and X 4 are both hydroxy.
  • the present invention provides a novel compound of formula (Ic) wherein A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , Q 1 and Q 2 are as defined in relation to formula I, and each X is sulfur; or salts or N-oxides thereof.
  • a 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , Q 1 and Q 2 are as defined in relation to formula I, and each X is sulfur; or salts or N-oxides thereof.
  • a , R , R , G , G , Q and Q are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • a group of particularly preferred compounds are compounds of formula (Ic) wherein X 2 , X 3 and X 4 are hydrogen and X 1 is methylthio.
  • a , A , A , A , R , R , G , G , Q and Q are as defined in relation to formula I, and each X is N-R 4 wherein R 4 is as defined in relation to formula I; or salts or N-oxides thereof.
  • the preferences for A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , Q 1 and Q 2 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
  • a group of particularly preferred compounds are compounds of formula (Ic) wherein X 2 , X 3 and X 4 are hydrogen and X 1 is ⁇ , ⁇ -dimethylamino.
  • a further group of particularly preferred compounds are compounds of formula (Ic) wherein X 1 , X 2 and X 4 are hydrogen and X 3 is ⁇ , ⁇ -dimethylamino.
  • Another group of particularly preferred compounds are compounds of formula (Ic) wherein X 2 , X 3 and X 4 are hydrogen and X 1 is N-ethylamino.
  • a further group of particularly preferred compounds are compounds of formula (Ic) wherein X 1 , X 2 and X 4 are hydrogen and X 3 is N-ethylamino.
  • Table 1 provides 119 compounds of formula (If) wherein Q 1 is 5-bromo-furan-2-yl.
  • Table 2 provides 119 compounds of formula (If) wherein Q 1 is 2-bromo-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 3 provides 119 compounds of formula (If) wherein Q 1 is 5-bromo-pyrid-3-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 4 provides 119 compounds of formula (If) wherein Q 1 is 2-chloro-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 5 provides 119 compounds of formula (If) wherein Q 1 is 3-chloro-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 6 provides 119 compounds of formula (If) wherein Q 1 is 2-chloro-pyrid-3-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 7 provides 119 compounds of formula (If) wherein Q 1 is 2-chloro-pyrid-4-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 8 provides 119 compounds of formula (If) wherein Q 1 is 6-chloro-pyrid-3-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 9 provides 119 compounds of formula (If) wherein Q 1 is 5-chloro-thiophen-2-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 10 provides 119 compounds of formula (If) wherein Q 1 is 3-chloro-5-trifluoromethyl- pyrid-2-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 11 provides 119 compounds of formula (If) wherein Q 1 is 4-cyano-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 12 provides 119 compounds of formula (If) wherein Q 1 is 2,5-dichloro-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 13 provides 119 compounds of formula (If) wherein Q 1 is 2,3-difluoro-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 14 provides 119 compounds of formula (If) wherein Q 1 is l,3-dimethyl-pyrazol-5-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 15 provides 119 compounds of formula (If) wherein Q 1 is 4-fluoro-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 16 provides 119 compounds of formula (If) wherein Q 1 is 2-fluoro-pyrid-3-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 17 provides 119 compounds of formula (If) wherein Q 1 is 2-fluoro-3-trifluoromethyl- phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 18 provides 119 compounds of formula (If) wherein Q 1 is 2 -methyl -phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 19 provides 119 compounds of formula (If) wherein Q 1 is 3 -methyl -pyrid-2-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 20 provides 119 compounds of formula (If) wherein Q 1 is 2-methylthio-pyrid-3-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 21 provides 119 compounds of formula (If) wherein Q 1 is 4-nitro-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 22 provides 119 compounds of formula (If) wherein Q 1 is phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 23 provides 119 compounds of formula (If) wherein Q 1 is l,2,3-thiadiazol-4-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 24 provides 119 compounds of formula (If) wherein Q 1 is thiophen-2-yl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • Table 25 provides 119 compounds of formula (If) wherein Q 1 is 2-chloro-5-nitro-phenyl and X 1 , X 2 , X 3 and X 4 have the values listed in Table 1.
  • the invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising at least one compound of formula (I)
  • a 1 , A 2 , A 3 and A 4 are independently of one another C-X or nitrogen, provided that no more than two of A 1 , A 2 , A 3 and A 4 are nitrogen;
  • each X is independently hydrogen, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl or Ci-C 4 alkoxy;
  • R 1 and R 2 are independently of one another hydrogen, Ci-C 4 alkyl or Ci-C 4 alkylcarbonyl;
  • G 1 and G 2 are independently of one another oxygen or sulfur;
  • Q 1 is aryl or aryl substituted by one to five substituents R 5 , which may be the same or different, or Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 5 , which may be the same or different;
  • R 3 is hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 6 cycloalkyl-Ci-C 4 -alkyl-, Ci-C 4 alkoxy-Ci- C 4 -alkyl-, Ci-C 4 haloalkoxy-Ci-C 4 -alkyl-, Ci-C 4 alkylthio-Ci-C 4 -alkyl-, Ci-C 4 haloalkylthio- Ci-C 4 -alkyl-, C 3 -Cscycloalkyl, C 3 -Cshalocycloalkyl, phenyl or phenyl substituted by one to five substituents R 5 , which may be the same or different, 2-naphthyl or 2-naphthyl substituted by one to five substituents R 5 , which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R 5
  • R 4 is hydrogen, halogen, cyano, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 6 cycloalkyl-Ci-C 4 -alkyl-, Ci-C 4 alkoxy-Ci-C 4 -alkyl-, Ci-C 4 haloalkoxy-Ci-C 4 -alkyl-, Ci-C 4 alkylthio-Ci-C 4 -alkyl-, d- C 4 haloalkylthio-C i -C 4 -alkyl-, C i -C 4 alkylsulfinyl-C i -C 4 -alkyl-, C i -C 4 haloalkylsulfinyl-C i - C 4 alkyl-, Ci-C 4 -alkylsulfonyl-Ci-C 4 -alkyl-, Ci-C 4 haloalkylsulf
  • Y 1 and Y 4 are independently of each other hydrogen, cyano, halogen, Ci-C 4 alkyl, Ci- C 4 haloalkyl, Ci-C 4 alkoxy-Ci-C 4 -alkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-
  • preferred values of A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , G 1 , G 2 , Q 1 , R 3 , R 4 , Y 1 , Y 2 , Y 3 and Y 4 are, in any combination, as set out below.
  • a 1 is C-X.
  • a 2 is C-X.
  • a 3 is C-X.
  • a 4 is C-X.
  • each X is independently hydrogen, fluoro, chloro, bromo, methyl, trifiuoromethyl or methoxy.
  • each X is independently hydrogen, fluoro, chloro, bromo, methyl or trifiuoromethyl.
  • each X is independently hydrogen, fluoro, methyl or trifiuoromethyl.
  • each X is independently hydrogen or fluoro.
  • each X is hydrogen.
  • R 1 is hydrogen, methyl, ethyl or acetyl.
  • R 1 is hydrogen, methyl or ethyl. Even more preferably R 1 is hydrogen or ethyl.
  • R 1 is hydrogen
  • R 2 is hydrogen, methyl, ethyl or acetyl.
  • R 2 is hydrogen, methyl or ethyl.
  • R 2 is hydrogen or ethyl.
  • R 2 is hydrogen
  • G 1 is oxygen
  • G 2 is oxygen
  • Q 1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Examples of such groups for Q 1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3- yl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro- pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5-trifluoromethyl-pyrid-2- yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, l ,3-dimethyl-lH-pyrazol-5-yl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2-fluoro-3-trifluoromethyl-phenyl, 2-methyl-phenyl, 3- methyl-pyrid-2
  • Q 1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Examples of more preferred groups for Q 1 are 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl,
  • Q 1 is phenyl substituted by one substituent selected from cyano, fluoro or chloro.
  • substituents selected from cyano, fluoro or chloro.
  • Examples of even more preferred groups for Q 1 are 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano-phenyl and 4-fluoro-phenyl.
  • Q 1 is 4-fluoro-phenyl.
  • R 3 is Ci-C 6 alkyl, Ci-C 6 haloalkyl, phenyl or phenyl substituted by one to five substituents R 5 , which may be the same or different. More preferably R 3 is Ci-C 6 alkyl or Ci-Cehaloalkyl.
  • R 3 is trifluoromethyl.
  • R 4 is Ci-C 6 alkyl, Ci-C 6 haloalkyl, phenyl or phenyl substituted by one to five substituents R 5 , which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R 5 , which may be the same or different.
  • R 4 is phenyl or phenyl substituted by one to five substituents selected from halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkoxy or Ci-C 3 haloalkoxy, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents selected from halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkoxy or Ci-C 3 halo- alkoxy, which may be the same or different.
  • R 4 is phenyl or phenyl substituted by one to five substituents selected from halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkoxy or Ci-C 3 haloalkoxy, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents selected from halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkoxy or Ci-C 3 halo- alkoxy, which may be the same or different.
  • R 4 examples of such groups for R 4 are 4-bromo- phenyl, 4-chloro-phenyl, 4-cyano-phenyl, 3,4-dichloro-phenyl, 4-dif uoromethoxy-phenyl, 4- fluoro-phenyl, 4-methylsulfonyloxy-phenyl, 4-methylsulfonyl-phenyl, 4-methylthio-phenyl, 4-nitro-phenyl, phenyl, 4-trifluoromethoxy-phenyl and 4-trifluoromethyl-phenyl.
  • R 4 is phenyl or phenyl substituted by one substituent selected from halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl.
  • substituents selected from halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl.
  • Examples of such preferred groups for R 4 are 4-chloro- phenyl, 4-fluoro-phenyl and 4-trifluoromethyl-phenyl.
  • Y 1 is cyano, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl.
  • Y 1 is cyano, chloro, methyl or trifluoromethyl.
  • Y 1 is methyl or ethyl.
  • Y 1 is methyl
  • Y 2 is hydrogen, fluoro, chloro or methyl.
  • Y 2 is hydrogen
  • Y 3 is hydrogen, fluoro, chloro or methyl.
  • Y 3 is hydrogen
  • Y 4 is cyano, chloro, methyl, ethyl or trifluoromethyl.
  • Y 4 is cyano, chloro, methyl or trifluoromethyl.
  • Y 4 is methyl or ethyl.
  • Y 4 is methyl.
  • One preferred embodiment of the embodiment (C) are compounds of formula (la) wherein A 1 , A 2 , A 3 , A 4 are CH.
  • Another preferred embodiment of the embodiment (C) are compounds of formula (lb) wherein A 1 is C-F, and A 2 , A 3 , and A 4 are CH.
  • a further preferred embodiment of the embodiment (C) are compounds of formula
  • Yet another preferred embodiment of the embodiment (C) are compounds of formula (Id) wherein A 4 is C-F, and A 1 , A 2 , and A 3 are CH.
  • One preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- dimethy 1-pheny 1.
  • Another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2-ethyl-6- methy 1-pheny 1.
  • a further preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- diethy 1-pheny 1.
  • Yet another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2- methoxymethyl-6-methyl-phenyl.
  • One preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- dimethy 1-pheny 1.
  • Another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2-ethyl-6- methy 1-pheny 1.
  • a further preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- diethy 1-pheny 1.
  • Q 2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2- methoxymethyl-6-methyl -phenyl.
  • One preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2,6-dimethyl-phenyl.
  • Another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2-ethyl-6-methyl-phenyl.
  • a further preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q 2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2,6-diethyl-phenyl.
  • Y 1 and Y 4 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkylthio, Ci-Cshaloalkylthio, Ci-Csalkylsulfinyl, Ci-Cshaloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-Cshaloalkylsulfonyl.
  • Y 1 and Y 4 are the same as set out for compounds of formula (I) except that Y 1 and Y 4 cannot be methoxymethyl.
  • Table 1 provides 26 compounds of formula (la) wherein R 4 is 4-bromo-phenyl and Q 1 has the values listed in the table below.
  • Table 2 provides 26 compounds of formula (la) wherein R 4 is 4-chloro-phenyl and Q 1 has the values listed in Table 1.
  • Table 3 :
  • Table 3 provides 26 compounds of formula (la) wherein R 4 is 4-cyano-phenyl and Q 1 has the values listed in Table 1.
  • Table 4 provides 26 compounds of formula (la) wherein R 4 is 3,4-dichloro-phenyl and Q 1 has the values listed in Table 1.
  • Table 5 provides 26 compounds of formula (la) wherein R 4 is 4-difluoromethoxy-phenyl and Q 1 has the values listed in Table 1.
  • Table 6 provides 26 compounds of formula (la) wherein R 4 is 4-fluoro-phenyl and Q 1 has the values listed in Table 1.
  • Table 7 provides 26 compounds of formula (la) wherein R 4 is 4-methylsulfonyloxy-phenyl and Q 1 has the values listed in Table 1.
  • Table 8 provides 26 compounds of formula (la) wherein R 4 is 4-methylsulfonyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 9 provides 26 compounds of formula (la) wherein R 4 is 4-methylthio-phenyl and Q 1 has the values listed in Table 1.
  • Table 10 provides 26 compounds of formula (la) wherein R 4 is 4-nitro-phenyl and Q 1 has the values listed in Table 1.
  • Table 11 provides 26 compounds of formula (la) wherein R 4 is phenyl and Q 1 has the values listed in Table 1.
  • Table 12 provides 26 compounds of formula (la) wherein R 4 is 4-trifluoromethoxy-phenyl and Q 1 has the values listed in Table 1.
  • Table 13 provides 26 compounds of formula (la) wherein R 4 is 4-trifluoromethyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 14 provides 26 compounds of formula (lb) wherein R 4 is 4-chloro-phenyl and Q 1 has the values listed in Table 1.
  • Table 15 provides 26 compounds of formula (lb) wherein R 4 is 4-fluoro-phenyl and Q 1 has the values listed in Table 1.
  • Table 16 provides 26 compounds of formula (lb) wherein R 4 is 4-trifluoromethyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 17 provides 26 compounds of formula (Ic) wherein R 4 is 4-chloro-phenyl and Q 1 has the values listed in Table 1.
  • Table 18 provides 26 compounds of formula (Ic) wherein R 4 is 4-fluoro-phenyl and Q 1 has the values listed in Table 1.
  • Table 19 provides 26 compounds of formula (Ic) wherein R 4 is 4-trifluoromethyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 20 provides 26 compounds of formula (Id) wherein R 4 is 4-chloro-phenyl and Q 1 has he values listed in Table 1.
  • Table 21 provides 26 compounds of formula (Id) wherein R 4 is 4-fluoro-phenyl and Q 1 has the values listed in Table 1.
  • Table 22 provides 26 compounds of formula (Id) wherein R 4 is 4-trifluoromethyl-phenyl and Q 1 has the values listed in Table 1.
  • the invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising at least one compound of formula (I)
  • a 1 , A 2 , A 3 and A 4 are independently of one another C-X or nitrogen, provided that no more than two of A 1 , A 2 , A 3 and A 4 are nitrogen;
  • each X is independently hydrogen, halogen, cyano, Ci-C 4 alkyl, Ci-C 4 haloalkyl or Ci- C 4 alkoxy;
  • R 1 and R 2 are independently of one another hydrogen, Ci-C 4 alkyl or Ci-C 4 alkylcarbonyl; G 1 and G 2 are independently of one another oxygen or sulfur;
  • Q 1 is aryl or aryl substituted by one to five substituents R 3 , which may be the same or different, or Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 3 , which may be the same or different;
  • each R 3 is independently cyano, nitro, hydroxy, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 2 - C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halo- cycloalkyl, Ci-C 3 alkoxy, Ci-C 3 haloalkoxy, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkyl- sulfinyl, Ci-C 3 alkylsulfonyl, Ci-Cshaloalkylsulfonyl, amino, Ci- C 4 alkylamino, di-(Ci-C 4 alkyl)amino, Ci-C 4 alkylcarbonyl, Ci-C 4 alkyl
  • Q 2 is a moiety of formula (II) or (III)
  • Y 1 and Y 5 are independently of each other hydrogen, cyano, halogen, Ci-C 4 alkyl, Ci-C 4 halo- alkyl, Ci-C 4 alkoxy-Ci-C 4 -alkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, d- C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 3 is C 2 -C 6 perfiuoroalkyl, Ci-C 6 perfluoroalkylthio, Ci-C 6 perfluoroalkylsulfinyl or Ci-C 6 per- fluoroalkylsulfonyl;
  • Y 2 and Y 4 are independently of each other hydrogen, halogen or Ci-C 4 alkyl;
  • Y 6 and Y 9 are independently of each other hydrogen, cyano, halogen, Ci-C 4 alkyl, Ci-C 4 halo- alkyl, Ci-C 4 alkoxy-Ci-C 4 -alkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, d- C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 8 is Ci-C 4 haloalkoxy, C 2 -C 6 perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C 6 perfluoroalkyl- sulfinyl or Ci-C 6 perfluoroalkylsulfonyl;
  • Y 7 is hydrogen, halogen or Ci-C 4 alkyl
  • the preferred values of A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , G 1 , G 2 , Q 1 , Q 2 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are, in any combination, as set out below.
  • a 1 is C-X.
  • a 2 is C-X.
  • a 3 is C-X.
  • a 4 is C-X.
  • each X is independently hydrogen, fluoro, chloro, bromo, cyano, methyl, trifluoromethyl or methoxy.
  • each X is independently hydrogen, fluoro, chloro, bromo, cyano, methyl or trifluoromethyl.
  • each X is independently hydrogen, fluoro, methyl or trifluoromethyl.
  • each X is independently hydrogen or fluoro.
  • each X is hydrogen.
  • R 1 is hydrogen, methyl, ethyl or acetyl.
  • R 1 is hydrogen, methyl or ethyl.
  • R 1 is hydrogen or ethyl.
  • R 1 is hydrogen
  • R 2 is hydrogen, methyl, ethyl or acetyl.
  • R 2 is hydrogen, methyl or ethyl.
  • R 2 is hydrogen or ethyl.
  • R 2 is hydrogen
  • G 1 is oxygen
  • G 2 is oxygen
  • Q 1 is phenyl, pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl, or phenyl, pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methyl- sulfmyl, methylsulfonyl or phenyl.
  • Examples of preferred groups for Q 1 are biphenyl-4-yl, 5- bromo-furan-2-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 3- chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2- methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3- yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-2,4,5-trifluoro- phenyl, 3 -chloro-5 -trifluoromethyl -pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-
  • Q 1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Examples of more preferred groups for Q 1 are biphenyl-4-yl, 5- bromo-furan-2-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 3- chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2- methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3 yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5-trifluoro- methyl-pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,
  • Q 1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Examples of even more preferred groups for Q 1 are biphenyl-4-yl, 3-chloro-2-fluoro-phenyl, 5-chloro- 2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2-methyl-phenyl, 2-chloro-phenyl, 3- chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3-chloro-5- trifluoromethyl-pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro- phenyl, 2-fluoro-pyrid-3-yl, 3-fluoro-pyrid
  • Q 1 is phenyl substituted by one substituent selected from cyano, fluoro or chloro.
  • substituents selected from cyano, fluoro or chloro.
  • Q 1 is 2-chloro- phenyl, 3-chloro-phenyl, 4-cyano-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl and 4-fluoro- phenyl.
  • Q 1 is 4-fluoro-phenyl.
  • Q 1 is aryl or aryl substituted by one to five substituents R 3 , which may be the same or different.
  • Q 1 is phenyl or phenyl substituted by one to four substituents
  • Examples of preferred groups for Q 1 are biphenyl-4-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo-phenyl, 3-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2- methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 3-chloro-2,4,5- trifluoro-phenyl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3- difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-4-nitro-phenyl, 3-fluoro-4-nitro- phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3-tri
  • Q 1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of more preferred groups for Q 1 are biphenyl-4-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo- phenyl, 3-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3- chloro-2-methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro- phenyl, 2,3-difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-4-nitro-phenyl, 3-fluoro-4 nitro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro
  • Q 1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of even more preferred groups for Q 1 are biphenyl-4-yl, 3-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro- phenyl, 3 -chloro-2 -hydroxy-phenyl, 3-chloro-2-methyl-phenyl, 2-chloro-phenyl, 3-chloro- phenyl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3- trifluoromethyl -phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 4-fluoro-3-trifluoromethyl- phenyl, 2-methoxy-phenyl, 4-methoxy-phenyl, 2-methyl-phenyl,
  • Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 3 , which may be the same or different.
  • Q 1 is heteroaryl or heteroaryl substituted by one to five substituents R 3 , which may be the same or different.
  • Q 1 is pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl, or pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of preferred groups for Q 1 are 5-bromo-furan-2-yl, 5- bromo-pyrid-3-yl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro- thiophen-2-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 2,5-dimethyl-2H-pyrazol-3-yl, 2- fluoro-pyrid-3-yl, 3-fluoro-pyrid-4-yl, furan-2-yl, lH-imidazol-4-yl, 4-methoxy-thiophen-3- yl, 5-methyl-3-phenyl-isoxazol-4-yl, 5-methyl-l-phenyl-lH-pyrazol-4-yl, 4-methyl-2- phenyl-pyrimid-5-yl, 4-methyl-2-phenyl-thiazol-5-yl,
  • Q 1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of more preferred groups for Q 1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2- chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro- 5-trifluoromethyl-pyrid-2-yl, 2,5-dimethyl-2H-pyrazol-3-yl, 2-fluoro-pyrid-3-yl, 3-fluoro- pyrid-4-yl, furan-2-yl, 4-methoxy-thiophen-3-yl, 5-methyl-l-phenyl-lH-pyrazol-4-yl, 3- methyl-pyrid-2-yl, 4-methyl- l,2,3-thiadiazol-5-yl, 2-methylthio-pyrid-3-yl, l-methyl-3- trifluoromethyl-lH-pyrazol-4-yl,
  • Q 1 is pyridyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of even more preferred groups for Q 1 are 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 2-fluoro-pyrid-3-yl, 3-fluoro-pyrid-4-yl, 3-methyl- pyrid-2-yl, 2-methylthio-pyrid-3-yl, pyrid-3-yl and pyrid-4-yl.
  • Q 2 is a moiety of formula (II).
  • Y 1 is cyano, chloro, bromo, methyl, ethyl, trifluoromethyl or
  • Y 1 is cyano, chloro, bromo, methyl or trifluoromethyl.
  • Y 1 is methyl or ethyl.
  • Y 1 is methyl
  • Y 2 is hydrogen, fluoro, chloro or methyl. Most preferably Y 2 is hydrogen.
  • Y 3 is heptafiuoropropyl, heptafluoroprop-2-yl, heptafiuoropropylthio, heptafiuoropropylsulfinyl, heptafluoropropylsulfonyl, heptafiuoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, heptafiuoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
  • Y 3 is heptafluoroprop-2-yl.
  • Y 4 is hydrogen, fiuoro, chloro or methyl.
  • Y 4 is hydrogen
  • Y 5 is cyano, chloro, bromo, methyl, ethyl or trifiuoromethyl.
  • Y 5 is cyano, chloro, bromo, methyl or trifiuoromethyl.
  • Y 5 is methyl or ethyl.
  • Y 5 is methyl
  • Y 6 is cyano, chloro, bromo, methyl, ethyl, trifiuoromethyl or methoxymethy 1.
  • Y 6 is cyano, chloro, bromo, methyl or trifiuoromethyl.
  • Y 6 is methyl or ethyl.
  • Y 6 is methyl
  • Y 7 is hydrogen, fiuoro, chloro or methyl.
  • Y 7 is hydrogen
  • Y 8 is heptafiuoropropyl, heptafluoroprop-2-yl, heptafiuoropropylthio, heptafiuoropropylsulfinyl, heptafluoropropylsulfonyl, heptafiuoroprop-2-ylthio, heptafluoroprop-2-ylsulfmyl, heptafiuoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
  • Y 8 is heptafluoroprop-2-yl.
  • Y 9 is cyano, chloro, bromo, methyl, ethyl, trifiuoromethyl or methoxymethy 1.
  • Y 9 is cyano, chloro, bromo, methyl or trifiuoromethyl.
  • Y 9 is methyl or ethyl.
  • Y 9 is methyl
  • One preferred embodiment of the embodiment (D) are compounds of formula (la) wherein A 1 , A 2 , A 3 , A 4 are CH.
  • Another preferred embodiment of the embodiment (D) are compounds of formula (lb) wherein A 1 is C-F, and A 2 , A 3 , and A 4 are CH.
  • a further preferred embodiment of the embodiment (D) are compounds of formula (Ic) wherein A 2 is C-F, and A 1 , A 3 , and A 4 are CH.
  • Yet another preferred embodiment of the embodiment (D) are compounds of formula (Id) wherein A 3 is C-F, and A 1 , A 2 , and A 4 are CH.
  • Yet a further preferred embodiment of the embodiment (D) are compounds of formula (Ie) wherein A 4 is C-F, and A 1 , A 2 , and A 3 are CH.
  • Another preferred embodiment of the embodiment (D) are compounds of formula (If) wherein A 1 is C-CN, and A 2 , A 3 , and A 4 are CH.
  • a further preferred embodiment of the embodiment (D) are compounds of formula (Ig) wherein A 2 is C-CN, and A 1 , A 3 , and A 4 are CH.
  • Yet another preferred embodiment of the embodiment (D) are compounds of formula (Ih) wherein A 3 is C-CN, and A 1 , A 2 , and A 4 are CH.
  • Yet a further preferred embodiment of the embodiment (D) are compounds of formula (Ij) wherein A 4 is C-CN, and A 1 , A 2 , and A 3 are CH.
  • One preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q 2 is 2,6-dimethyl-4-perfluoroisopropyl-phenyl.
  • Another preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q 2 is 2-ethyl-6-methyl-4-perfluoroisopropyl-phenyl.
  • a further preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q 2 is 2,6-diethyl-4-perfluoroisopropyl-phenyl.
  • Yet another preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q 2 is 2-methoxymethyl-6-methyl-4-perfluoroisopropyl-phenyl.
  • Yet another preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q 2 is 2-methyl-4-perfluoroisopropyl-phenyl.
  • each X is independently hydrogen, halogen, Ci-C 4 alkyl or trifluoromethyl.
  • Q 1 is aryl or aryl substituted by one to five substituents R 3 , which may be the same or different, or Q 1 is heteroaryl or heteroaryl substituted by one to five substituents R 3 , which may be the same or different.
  • each R 3 is independently cyano, nitro, hydroxy, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 - C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, Ci-C 3 alkoxy, Ci- C 3 haloalkoxy, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfmyl, Ci-C 3 haloalkyl- sulfmyl, Ci-C 3 alkylsulfonyl, Ci-C 3 haloalkylsulfonyl, Ci-C 4 alkylamino, di-(Ci-C 4 alkyl)-
  • Y 1 and Y 5 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkylthio, Ci-Cshaloalkylthio, Ci-C 3 alkylsulfinyl, Ci-Cshaloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-Cshaloalkylsulfonyl.
  • Y 6 and Y 9 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, Ci-C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl.
  • a , A A ⁇ A , R , R G z and Q z are as defined in relation to formula (I); or salts or N-oxides thereof.
  • Table 1 provides 25 compounds of formula (la) wherein Q 2 is 2,6-dimethyl-4- perfluoroisopropyl-phenyl and Q 1 has the values listed in the table below.
  • Table 2 provides 25 compounds of formula (la) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 3 provides 25 compounds of formula (la) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 4 provides 25 compounds of formula (lb) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 5 provides 25 compounds of formula (lb) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 6 provides 25 compounds of formula (lb) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 7 provides 25 compounds of formula (Ic) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 8 provides 25 compounds of formula (Ic) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 9 provides 25 compounds of formula (Ic) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 10 provides 25 compounds of formula (Id) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 11 provides 25 compounds of formula (Id) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 12 provides 25 compounds of formula (Id) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 13 provides 25 compounds of formula (Ie) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 14 provides 25 compounds of formula (Ie) wherein Q 2 is 2 -methyl -4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 15 provides 25 compounds of formula (Ie) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 16 provides 25 compounds of formula (If) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 17 provides 25 compounds of formula (If) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 18 provides 25 compounds of formula (If) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 19 provides 25 compounds of formula (Ig) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 20 provides 25 compounds of formula (Ig) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 21 provides 25 compounds of formula (Ig) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 22 provides 25 compounds of formula (Ih) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 23 provides 25 compounds of formula (Ih) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 24 provides 25 compounds of formula (Ih) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 25 provides 25 compounds of formula (Ij) wherein Q 2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 26 provides 25 compounds of formula (Ij) wherein Q 2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • Table 27 provides 25 compounds of formula (Ij) wherein Q 2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q 1 has the values listed in Table 1.
  • the invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising at least one compound of formula (I)
  • a 1 , A 2 , A 3 and A 4 are independently of one another C-R 3 , C-R 5 or nitrogen, provided that at least one of A 1 , A 2 , A 3 and A 4 is C-R 3 and no more than two of A 1 , A 2 , A 3 and A 4 are nitrogen;
  • R 1 and R 2 are independently of each other hydrogen, Ci-C 4 alkyl, C 2 -C 4 alkenyl, C 2 - C 4 alkynyl, Ci-C 4 alkylcarbonyl, hydroxy, Ci-C 4 alkylcarbonyloxy, arylcarbonyloxy or arylcarbonyloxy wherein the aryl ring is substituted by one to five substituents independently selected from halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy or Ci-C 4 haloalkoxy;
  • G 1 and G 2 are independently of each other oxygen or sulfur
  • each R 3 is independently cyano, thiocyanato, aminothiocarbonyl, N-Ci-C 4 alkyl-amino- thiocarbonyl or N,N-di-Ci-C 4 alkyl-aminothiocarbonyl;
  • each R 5 is independently hydrogen, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl or Ci-C 4 alkoxy;
  • Q 1 is aryl or aryl substituted by one to five substituents R 6 , which may be the same or different, or
  • Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 6 , which may be the same or different;
  • each R 6 is independently cyano, nitro, hydroxy, halogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, Ci- C 4 alkoxy-Ci-C 4 -alkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 3 - C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, Ci-C 6 alkoxy, Ci-C 6 haloalkoxy, Ci-C 4 alkoxy-Ci-C 4 - alkoxy, Ci-C 6 alkylthio, Ci-C 6 haloalkylthio, Ci-C 6 alkylsulfinyl, Ci-C 6 haloalkylsulfmyl, Ci- Cealkylsulfonyl, Ci-Cehaloalkylsulfon
  • Q 2 is a moiety of formula (II) or (III)
  • Y 1 and Y 5 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci- C 4 alkoxy-Ci-C 4 -alkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, Ci- C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 3 is C 2 -C 6 perfluoroalkyl, Ci-C 6 perfluoroalkylthio, Ci-C 6 perfluoroalkylsulfinyl or Ci-C 6 per- fluoroalkylsulfonyl;
  • Y 2 and Y 4 are independently of each other hydrogen, halogen or Ci-C 4 alkyl;
  • Y 6 and Y 9 are independently of each other cyano, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Q- C 4 alkoxy-Ci-C 4 -alkyl, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfinyl, Q- C 3 haloalkylsulfinyl, Ci-C 3 alkylsulfonyl or Ci-C 3 haloalkylsulfonyl;
  • Y 8 is Ci-C 4 haloalkoxy, C 2 -C 6 perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C 6 perfluoroalkyl- sulfinyl or Ci-C 6 perfluoroalkylsulfonyl;
  • Y 7 is hydrogen, halogen or Ci-C 4 alkyl;
  • the preferred values of A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , G 1 , G 2 , R 3 , R 5 , Q 1 , R 6 , Q 2 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 and Y 9 are, in any combination, as set out below.
  • a 1 is C-R 3 or C-R 5 .
  • a 2 is C-R 3 or C-R 5 .
  • a 3 is C-R 3 or C-R 5 .
  • a 4 is C-R 3 or C-R 5 .
  • a 1 , A 2 , A 3 and A 4 are C-R 3 .
  • a 1 , A 2 , A 3 and A 4 are C-R 3 .
  • a 1 , A 2 , A 3 and A 4 is C-R 3 .
  • R 1 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl, hydroxy, acetyloxy or benzoyloxy.
  • R 1 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl or hydroxy. Even preferably R 1 is hydrogen, methyl or ethyl.
  • R 1 is hydrogen or methyl.
  • R 1 is hydrogen
  • R 2 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl, hydroxy, acetyloxy or benzoyloxy.
  • R 2 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl or hydroxy.
  • R 2 is hydrogen, methyl or ethyl.
  • R 2 is hydrogen or methyl.
  • R 2 is hydrogen
  • G 1 is oxygen
  • G 2 is oxygen
  • each R 3 is independently cyano, thiocyanato or aminothiocarbonyl.
  • each R 3 is independently cyano or thiocyanato.
  • each R 3 is cyano.
  • each R 5 is independently hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl or methoxy. More preferably each R 5 is independently hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl.
  • each R 5 is independently hydrogen, fluoro, methyl or trifluoromethyl.
  • each R 5 is independently hydrogen or fluoro.
  • each R 5 is hydrogen.
  • Q 1 is aryl or aryl substituted by one to five substituents R 6 , which may be the same or different, or Q 1 is heteroaryl or heteroaryl substituted by one to five substituents R 6 , which may be the same or different.
  • Q 1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Examples of such more preferred groups for Q 1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 2-chloro-4-fluoro-phenyl, 3- chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-methyl-phenyl, 2-chloro-4- nitro-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3 -chloro-5 -trifluoromethyl - pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-d
  • Q 1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Q 1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Most preferably Q 1 is phenyl substituted by one or two substituents selected from chloro, fluoro or methyl.
  • Q 1 is 2-chloro-4-fluoro-phenyl.
  • Q 1 is 3-chloro-2-fluoro-phenyl.
  • Q 1 is 5-chloro-2-fluoro-phenyl.
  • Q 1 is 3-chloro-2-methyl-phenyl.
  • Q 1 is 2-chloro-phenyl.
  • Q 1 is 3-chloro-phenyl.
  • Q 1 is 4-cyano-phenyl.
  • Q 1 is 2,5-dichloro-phenyl.
  • Q 1 is 2,3-difluoro-phenyl.
  • Q 1 is 2-fluoro-phenyl
  • Q 1 is 4-fluoro-phenyl.
  • Q 1 is 2-methyl-phenyl
  • a particularly preferred group of compounds are compounds of formula (I) wherein Q 1 is aryl or aryl substituted by one to five substituents R 6 , which may be the same or different.
  • Q 1 is phenyl or phenyl substituted by one to four substituents
  • Q 1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Q 1 is phenyl or phenyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
  • Another particularly preferred group of compounds are compounds of formula (I) wherein Q 1 is heterocyclyl or heterocyclyl substituted by one to five substituents R 6 , which may be the same or different.
  • the heterocyclyl group is preferably a heteroaryl group.
  • Q 1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfinyl, methyl- sulfonyl or phenyl.
  • Q 1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Q 1 is pyridyl or pyridyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
  • Q 1 is pyridyl substituted by one to two substituents independently selected from chloro, fluoro or methyl.
  • each R 6 is independently cyano, nitro, hydroxy, halogen, Ci-C 6 alkyl, Ci- C 6 haloalkyl, Ci-C 4 alkoxy-Ci-C 4 -alkyl, C3-C 6 cycloalkyl, Ci-C 6 alkoxy, Ci-C 6 haloalkoxy, Ci- C 4 alkoxy-Ci-C 4 -alkoxy, Ci-C 6 alkylthio, Ci-C 6 alkylsulfonyl, N,N-di-(Ci-C 6 alkyl)amino, N,N- di-(Ci-C 6 alkyl)aminocarbonyl, N,N-di-(Ci-C 6 alkyl)aminosulfonyl, Ci-C 6 alkylcarbonyl, Ci- Cealkylcarbonyloxy, Ci-C 6 alkoxycarbonyl or Ci-Cealkylcarbonylamino.
  • each R 6 is independently cyano, nitro, hydroxy, bromo, chloro, fluoro, iodo, methyl, ethyl, n-propyl, prop-2-yl, n-butyl, tert-butyl, chloromethyl,
  • each R 6 is independently cyano, nitro, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, N,N-dimethylamino or methoxycarbonyl.
  • Q 2 is a moiety of formula (II).
  • Y 1 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl. More preferably Y 1 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
  • Y 1 is bromo, chloro, methyl, ethyl or methoxymethyl.
  • Y 1 is bromo, methyl or ethyl.
  • Y 1 is methyl or ethyl.
  • Y 1 is methyl
  • Y 2 is hydrogen, chloro, fluoro or methyl.
  • Y 2 is hydrogen
  • Y 3 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
  • Y 3 is C2-C 6 perfluoroalkyl, more preferably Y 3 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
  • Y 3 is heptafluoroprop-2-yl.
  • Y 3 is nonafluorobut-2-yl.
  • Y 4 is hydrogen, chloro, fluoro or methyl.
  • Y 4 is hydrogen
  • Y 5 is cyano, halogen, methyl, ethyl or trifluoromethyl.
  • Y 5 is cyano, bromo, chloro, methyl, ethyl or trifluoromethyl.
  • Y 5 is bromo, chloro, methyl or ethyl.
  • Y 5 is bromo, methyl or ethyl.
  • Y 5 is methyl or ethyl.
  • Y 5 is methyl
  • Y 6 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl. More preferably Y 6 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
  • Y 6 is bromo, chloro, methyl, ethyl or methoxymethyl.
  • Y 6 is bromo, methyl or ethyl.
  • Y 6 is methyl or ethyl.
  • Y 6 is methyl
  • Y 7 is hydrogen, chloro, fluoro or methyl.
  • Y 7 is hydrogen.
  • Y is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfmyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
  • Y 8 is C2-C 6 perfluoroalkyl, more preferably Y 8 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
  • Y 8 is heptafluoroprop-2-yl.
  • Y 8 is nonafluorobut-2-yl.
  • Y 9 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl.
  • Y 9 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
  • Y 9 is bromo, chloro, methyl, ethyl or methoxymethyl.
  • Y 9 is bromo, methyl or ethyl.
  • Y 9 is methyl or ethyl.
  • Y 9 is methyl
  • a preferred embodiment of the embodiment (E) are compounds of formula (la) wherein A 1 is C-CN, and A 2 , A 3 , A 4 are CH.
  • a preferred embodiment of the embodiment (E) are compounds of formula (lb) wherein A 2 is C-CN, and A 1 , A 3 , and A 4 are CH.
  • a preferred embodiment of the embodiment (E) are compounds of formula (Ic) wherein A 3 is C-CN, and A 1 , A 2 , and A 4 are CH.
  • a preferred embodiment of the embodiment (E) are compounds of formula (Id) wherein A 4 is C-CN, and A 1 , A 2 , and A 3 are CH.
  • a preferred embodiment of the embodiment (E) are compounds of formula (Ie) wherein A 1 is C-CN, A 4 is C-F, and A 2 and A 3 are CH.
  • a preferred embodiment of the embodiment (E) are compounds of formula (If) wherein A 1 is C-CN, A 2 and A 4 are C-F, and A 3 is CH.
  • Q 2 is 2,6-dimethyl-4- (heptafluoroprop-2-yl)-phenyl.
  • Q 2 is 2-ethyl-6-methyl-4- (heptafluoroprop-2-yl)-phenyl.
  • Q 2 is 2,6-diethyl-4- (heptafluoroprop-2-yl)-phenyl. In a preferred embodiment of the embodiment (E) Q 2 is 2-methoxymethyl-6-methyl- 4-(heptafluoroprop -2 -yl)-pheny 1.
  • Q 2 is 2-bromo-6-methyl-4- (heptafluoroprop-2-yl)-phenyl.
  • Q 2 is 2-bromo-6-ethyl-4-
  • Q 2 is 2,6-dichloro-4- (heptafluoroprop-2-yl)-phenyl.
  • Q 2 is 2,6-dibromo-4- (heptafluoroprop-2-yl)-phenyl.
  • Q 2 is 2,6-dimethyl-4- (nonafluorobut-2-yl)-phenyl.
  • Q 2 is 2-ethyl-6-methyl-4- (nonafluorobut-2-yl)-phenyl.
  • Q 2 is 2,6-diethyl-4-(nonafluorobut-
  • Q 2 is 2-methoxymethyl-6-methyl- 4-(nonafluorobut-2-yl)-phenyl.
  • Q 2 is 2-bromo-6-methyl-4- (nonafluorobut-2-yl)-phenyl.
  • Q 2 is 2-bromo-6-ethyl-4- (nonafluorobut-2-yl)-phenyl.
  • Q 2 is 2,6-dichloro-4- (nonafluorobut-2-yl)-phenyl.
  • Q 2 is 2,6-dibromo-4-
  • R 1 and R 2 are identical to one embodiment of the embodiment (E) of the invention.
  • R 1 and R 2 independently of each other hydrogen, Ci-C 4 alkyl, or Ci-C 4 alkylcarbonyl.
  • the preferences for R 1 and R 2 are the same as set out for compounds of formula (I) except that R 1 and R 2 cannot be allyl, propargyl, hydroxy, acetyloxy or benzoyloxy.
  • each R 3 is independently cyano, thiocyanato or N-Ci-C 4 alkyl-aminothiocarbonyl.
  • the preferences for R 3 are the same as set out for compounds of formula (I) except that R 3 cannot be aminothiocarbonyl.
  • each R 5 is independently hydrogen, halogen, Ci-C 4 alkyl or trifluoromethyl.
  • the preferences for R 5 are the same as set out for compounds of formula (I) except that R 5 cannot be methoxy.
  • each R 6 is independently cyano, nitro, hydroxy, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, Ci-C 3 alkoxy, Ci- C 3 haloalkoxy, Ci-C 3 alkylthio, Ci-C 3 haloalkylthio, Ci-C 3 alkylsulfmyl, Ci-C 3 haloalkyl- sulfinyl, Ci-C 3 alkylsulfonyl, Ci-C 3 haloalkylsulfonyl, N-Ci-C 4 alkylamino, N,N-di-
  • Y 1 and Y 5 are
  • Y 1 and Y 5 are the same as set out for compounds of formula (I) except that Y 1 cannot be methoxymethyl.
  • Y 6 and Y 9 are
  • Y 6 and Y 9 are the same as set out for compounds of formula (I) except that Y 6 and Y 9 cannot be methoxymethyl.

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Abstract

The present invention relates to a pharmaceutical composition comprising at least one aminobenzamide derivative or a salt thereof for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans. The present invention further relates to mixtures of biologically active ingredients for use in methods of therapeutic treatment, in particular for use against parasitic invertebrate pests in or on animals, including mixtures comprising at least one aminobenzamide derivative or a salt thereof

Description

USE OF AMINOBEN AMIDE DERIVATIVES FOR CONTROLLING ANIMAL PARASITES
The invention relates to a composition comprising at least one aminobenzamide derivatives or a salt thereof for controlling animal parasites, veterinary pharmaceutical compositions comprising at least one aminobenzamide derivatives or a salt thereof for preventing infection with diseases transmitted through parasites, its use for the preparation of a veterinary pharmaceutical for controlling animal parasites, and a method for preventing infection with diseases transmitted through parasites. The compounds of the present invention are also usfull for medical uses.
The infestation of animals, domestic animals, companion animals and agricultural livestock alike, with parasites represents a problem. Often, the infested animals are infected with diseases transmitted through parasites, like e.g. lyme disease, a variety of sometimes fatal viral diseases or the immune system of the animals becomes weak due to the infestation, so that the animals become prone to other diseases, like e.g. bacterial infections. With the result that costly medicaments have to be administered, and, if the treated animals are agricultural livestock then the food safety is jeopardized. Additionally, the infestation of agricultural livestock with parasites is very often accompanied with a decrease in performance in terms of quality and quantity of produced meat, milk, egg, wool, or fur.
In particular, blood-sucking ectoparasites and ectoparasites causing myiasis are potential transmitters of a broad variety of pathogens besides all other secondary effects of the ectoparasitic infestation as there are blood-loss, irritation, inflammation, secondary bacterial infection, secondary parasiticidal infection (e.g. myiasis) and direct toxicosis (tick paralysis). Although there are several compounds known to combat animal parasites there is still a need for new compounds. Especially in the field of livestock the treated ectoparasites are often present in high numbers. Together with repeated treatments necessary to minimize damage to the host animals there is a steadily increasing risk that the ectoparasites are developing a resistance against the existing veterinary pharmaceuticals. There is also a need for veterinary pharmaceuticals which prevent the infestation of animals with parasites. And, moreover, for compounds which can prevent blood meal or lesions caused by ectoparasites and thus additionally can reduce the risk of transmitting vector-borne diseases to animals and humans. Compounds for combating agricultural pests are known from WO2007128410,
WO2008000438, WO2008012027, WO2008031534, WO2008074427, WO2008107091 , WO2009049845, WO2009049844, WO2010006725, WO2010127928, WO2010127927, WO2010127926, WO201 1095462 and WO201 1 1 13756
Therefore, in an embodiment (A), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000003_0001
wherein
A1, A2 and A3 are independently of one another C-X, N-X, nitrogen, oxygen or sulfur,
1 2 3 1 2 3 provided that two of A , A or A are C-X or nitrogen and that one of A , A or A is oxygen, sulfur or N-X;
each X is independently hydrogen, halogen, Ci-C4alkyl or trifluoromethyl;
R1 and R2 are independently of one another hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl; G' and G2 are independently of one another oxygen or sulfur;
Q1 is aryl or aryl substituted by one to five substituents R3, which may be the same or different, or Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R3, which may be the same or different; wherein
each R3 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2- C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-C6halo- cycloalkyl, Ci-C3alkoxy, Ci-Cshaloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkyl- sulfmyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, Ci-C4alkyl- amino, di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxy- carbonyl, Ci-C4alkylcarbonylamino or phenyl; and
Q2 is a moiety of formula (II) or (III)
Figure imgf000004_0001
wherein
Y1 and Y5 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci- C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkyl- sulfonyl or Ci-C3haloalkylsulfonyl;
Y3 is C2-C6perfiuoroalkyl, Ci-C6perfluoroalkylthio, Ci-C6perfluoroalkylsulfinyl or Ci-C6per- fluoroalkylsulfonyl;
Y2 and Y4 are independently of each other hydrogen, halogen or Ci-C4alkyl;
Y6 and Y9 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci- C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfmyl, Ci-C3haloalkylsulfmyl, Ci-C3alkyl- sulfonyl or Ci-C3haloalkylsulfonyl;
Y8 is Ci-C4haloalkoxy, C2-C6perfiuoroalkyl, Ci-C6perfluoroalkylthio, Ci-C6perfluoroalkyl- sulfmyl or Ci-Ceperfluoroalkylsulfonyl;
Y7 is hydrogen, halogen or Ci-C4alkyl;
or salts or N-oxides thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
Preferred values of A1, A2, A3, X, R1, R2, G1, G2, Q1, Q2, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are, in any combination, as set out below.
Preferably two of A1, A2 and A3 are C-X and one is sulfur, more preferably A1 and A3 are C-X and A2 is sulfur.
Preferably each X is independently hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl, more preferably hydrogen, fluoro, chloro, bromo or methyl, even more preferably hydrogen, chloro, bromo or methyl, most preferably hydrogen.
Preferably R1 is hydrogen, methyl, ethyl or acetyl, most preferably hydrogen.
Preferably R2 is hydrogen, methyl, ethyl or acetyl, most preferably hydrogen.
Preferably G1 is oxygen.
Preferably G2 is oxygen. Preferably Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, nitro or phenyl. More preferably Q1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Even more preferably Q1 is phenyl or pyridyl substituted by one to three substituents independently selected from cyano, fluoro, chloro or methyl. Especially preferred groups for Q1 are 5- bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro- phenyl, l,3-dimethyl-pyrazol-5-yl, 2-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2- fluoro-3-trifluoromethyl-phenyl, furan-2-yl, 2-methyl-phenyl, 3-methyl-pyrid-2-yl, 4- methylthio-phenyl, 2-methylthio-pyrid-3-yl, 4-nitro-phenyl, phenyl, pyrid-3-yl, pyrid-4-yl, 2- trifluoromethyl-phenyl and 4-trifluoromethyl-phenyl. Most especially preferred groups for Q1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 2-chloro-phenyl, 3-chloro- phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2- yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro- phenyl, l,3-dimethyl-pyrazol-5-yl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2-f uoro-3-trifluoro- methyl-phenyl, furan-2-yl, 2-methyl-phenyl, 3-methyl-pyrid-2-yl, 4-methylthio-phenyl, 4- nitro-phenyl, phenyl and pyrid-3-yl.
A particularly preferred group of compounds are compounds of formula (I) wherein Q1 is aryl or aryl substituted by one to five substituents R3, which may be the same or different.
Preferably Q1 is phenyl or phenyl substituted by one to three substituents
independently selected from cyano, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, nitro or phenyl. More preferably Q1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Even more preferably Q1 is phenyl substituted by one to three substituents independently selected from cyano, fluoro, chloro or methyl. Especially preferred groups for Q1 are 2-bromo-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano- phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 2-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro- 3 -trifluoromethyl -phenyl, 2-methyl-phenyl, 4-methylthio-phenyl, 4-nitro-phenyl, phenyl, 2- trifluoromethyl-phenyl and 4-trifluoromethyl-phenyl. Most especially preferred groups for Q1 are 2-bromo-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano-phenyl, 2,5-dichloro- phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3-trifluoromethyl-phenyl, 2-methyl- phenyl, 4-methylthio-phenyl, 4-nitro-phenyl and phenyl.
Another particularly preferred group of compounds are compounds of formula (I) wherein Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R3, which may be the same or different. The heterocyclyl group is preferably a heteroaryl group.
Preferably Q1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, nitro or phenyl. More preferably Q1 is pyridyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Even more preferably Q1 is pyridyl substituted by one to three substituents independently selected from cyano, fluoro, chloro or methyl.
Especially preferred groups for Q1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2-chloro- pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5- trifluoromethyl-pyrid-2-yl, l,3-dimethyl-pyrazol-5-yl, 2-fluoro-pyrid-3-yl, furan-2-yl, 3- methyl-pyrid-2-yl, 2-methylthio-pyrid-3-yl, pyrid-3-yl and pyrid-4-yl. More especially preferred groups for Q1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2-chloro-pyrid-3-yl, 2- chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3 -chloro-5 -trifluoromethyl - pyrid-2-yl, 3 -dimethyl -pyrazol-5-yl, 2-fluoro-pyrid-3-yl, furan-2-yl, 3-methyl-pyrid-2-yl and pyrid-3-yl. Most especially preferred groups for Q1 are 5-bromo-pyrid-3-yl, 2-chloro-pyrid- 3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 2- fluoro-pyrid-3-yl, 3-methyl-pyrid-2-yl and pyrid-3-yl.
Preferably Q2 is a moiety of formula (II). Especially preferred groups for Q2 are 4- heptafluoroisopropyl-2,6-dimethyl-phenyl and 4-heptafluoroisopropyl-2,6-diethyl-phenyl.
Preferably Y1 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
Preferably Y2 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen. Preferably Y3 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfmyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl, most preferably heptafluoroprop-2-yl.
Preferably Y4 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen.
Preferably Y5 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
Preferably Y6 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
Preferably Y7 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen.
Preferably Y8 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfmyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl, most preferably heptafluoroprop-2-yl.
Preferably Y9 is cyano, chloro, methyl, ethyl or trifluoromethyl, more preferably methyl or ethyl, most preferably methyl.
A particularly preferred group of compounds of the embodiment (A) are compounds of formula (la)
Figure imgf000007_0001
1 2 1 2 1 2 1 2 wherein R , R G , G Q1 and Qz are as defined in relation to formula (I) and X and X are independently defined as X in relation to formula (I); or salts or N-oxides thereof. The preferences for R1, R2, G1, G2, Q1, Q2, X, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I). A group of most particularly preferred compounds are compounds of formula (la) wherein X1 and X2 are both hydrogen.
Another group of particularly preferred compounds are compounds of formula (lb)
Figure imgf000008_0001
1 2 1 2 1 2 1 2 wherein R , R G , Gz, Q1 and Qz are as defined in relation to formula (I) and X and X are independently defined as X in relation to formula (I); or salts or N-oxides thereof. The preferences for R1, R2, G1, G2, Q1, Q2, X, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I). A group of most particularly preferred compounds are compounds of formula (lb) wherein X1 and X2 are both hydrogen. A further group of most particularly preferred compounds are compounds of formula (lb) wherein X1 is bromo and X2 is hydrogen.
A further group of particularly preferred compounds od the embodiment (A) are compounds of formula (Ic)
Figure imgf000008_0002
1 2 1 2 1 2 1 2 wherein R , R G , G Q1 and Qz are as defined in relation to formula (I) and X and X are independently defined as X in relation to formula (I); or salts or N-oxides thereof. The preferences for R1, R2, G1, G2, Q1, Q2, X, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I). A group of most particularly preferred compounds are compounds of formula (Ic) wherein X1 and X2 are both hydrogen. A further group of most particularly preferred compounds are compounds of formula (Ic) wherein X1 is hydrogen and X2 is chloro. Yet a further group of most particularly preferred compounds are compounds of formula (Ic) wherein X1 is hydrogen and X2 is bromo. Another group of most particularly preferred compounds are compounds of formula (Ic) wherein X1 is hydrogen and X2 is methyl. One embodiment of the embodiment (A) the present invention provides a compound of formula (Ix)
Figure imgf000009_0001
wherein
A1, A2 and A3 are independently of one another carbon, nitrogen, nitrogen oxide, oxygen or sulfur with the proviso that at least one of A1, A2 or A3 is not carbon and no more than one of A1, A2 or A3 is oxygen or sulfur;
R1 and R2 are independently of one another hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl;
G1 and G2 are independently of one another oxygen or sulfur;
X are independently of one another halogen, Ci-C3alkyl or trifluoromethyl;
n is 0, 1 , 2 or 3;
Q1 is aryl or aryl substituted by one to five substituents independently selected from R3, or heterocyclyl or heterocyclyl substituted by one to five substituents independently selected from R3; wherein
R3 are independently of one another cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4halo- alkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-Cehalocycloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci- C3alkylsulfinyl, Ci-C3haloalkylsulfmyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, Ci- C4alkylamino, di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy,
Figure imgf000009_0002
C4alkoxycarbonyl, Ci-C4alkylcarbonylamino or phenyl; and
Q2 is a moiety of formula (II) or (III)
Figure imgf000009_0003
wherein Y1 and Y5 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci- C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkyl- sulfonyl or Ci-C3haloalkylsulfonyl;
Y3 is C2-C6perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C6perfluoroalkylsulfinyl or Ci-C6per- fluoroalkylsulfonyl;
Y2 and Y4 are independently of each other hydrogen, halogen or Ci-C4alkyl;
Y6 and Y9 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, d- C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkyl- sulfonyl or Ci-C3haloalkylsulfonyl;
Y8 is Ci-C4haloalkoxy, C2-C6perfluoroalkyl, Ci-C6perfluoroalkylthio, Ci-C6perfluoroalkyl- sulfinyl or Ci-C6perfluoroalkylsulfonyl;
Y7 is hydrogen, halogen or Ci-C4alkyl;
or salts or N-oxides thereof. Preferably two of A1, A2 and A3 are carbon and one is sulfur, most preferably A1 and
A3 are carbon and A2 is sulfur.
Preferably X is fluoro, chloro, methyl or trifluoromethyl, most preferably fluoro, chloro or methyl.
Preferably n is 0, 1 or 2, even more preferably 0 or 1 , most preferably 0.
The preferences for R1, R2, G1, G2, Q1, Q2, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
The compounds in Tables 1 to 7 below illustrate the compounds of the invention according to the embodiment (A).
Table 1 :
Table 1 provides 29 compounds of formula (la') wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropy 1-pheny 1.
Figure imgf000011_0001
Compound numbers Q1
1.01 5-bromo-furan-2-yl
1.02 2-bromo-phenyl
1.03 5 -bromo -pyrid-3 -yl
1.04 2-chloro-phenyl
1.05 3-chloro-phenyl
1.06 2-chloro-pyrid-3-yl
1.07 2-chloro-pyrid-4-yl
1.08 6-chloro-pyrid-3-yl
1.09 5-chloro-thiophen-2-yl
1.10 3 -chloro-5 -trifluoromethyl-pyrid-2- yl
1.11 4-cyano-phenyl
1.12 2,5-dichloro-phenyl
1.13 2,3-difluoro-phenyl
1.14 1 ,3 -dimethyl-pyrazol-5 -yl
1.15 2-fluoro-phenyl
1.16 4-fluoro-phenyl
1.17 2-fluoro-pyrid-3 -yl
1.18 2-fluoro-3 -trifluoromethyl -phenyl
1.19 furan-2-yl
1.20 2-methyl -phenyl
1.21 3 -methyl -pyrid-2-yl
1.22 4-methylthio-phenyl
1.23 2-methylthio-pyrid-3-yl
1.24 4-nitro-phenyl Compound numbers Q
1.25 phenyl
1.26 pyrid-3-yl
1.27 pyrid-4-yl
1.28 2-trifluoromethyl-phenyl
1.29 4-trifluoromethyl-phenyl
Table 2:
Table 2 provides 29 compounds of formula (lb') wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000012_0001
Table 3:
Table 3 provides 29 compounds of formula (Ic') wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000012_0002
HN Table 4:
Table 4 provides 29 compounds of formula (lb") wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000013_0001
Table 5:
Table 5 provides 29 compounds of formula (Ic") wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000013_0002
Table 6:
Table 6 provides 29 compounds of formula (Ic'") wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000013_0003
Table 7:
Table 7 provides 29 compounds of formula (Ic"") wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000014_0001
Preferred compounds according to the embodiment (A) are
2-chloro-N-{4-[2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)- phenylcarbamoyl] -thiophen-2-yl} -nicotinamide;
5-[(thiophene-2-carbonyl)-amino]-thiophene-3-carboxylic acid [2, 6-dimethyl-4-( 1,2,2,2- tetrafluoro- 1 -trifluoromethyl-ethyl)-phenyl] -amide;
5-[(furanne-2-carbonyl)-amino]-thiophene-3-carboxylic acid [2,6-diethyl-4-(l ,2,2,2- tetrafluoro- 1 -trifluoromethyl-ethyl)-phenyl] -amide;
And the compounds of Tabel A, B, C, D, E, F, and G
Table A: Compounds of formula (la'):
Figure imgf000014_0002
Compound Q Q2
No.
Al 4-heptafluoroisopropyl-2,6- dimethyl-phenyl
CI
A2 4-heptafluoroisopropyl-2,6- dimethyl-phenyl
Figure imgf000015_0001
Figure imgf000016_0001
Figure imgf000017_0001
Figure imgf000018_0001
Figure imgf000019_0001
Compound Q1 Q2
No.
A65 CF3 4-heptafluoroisopropyl-2,6- diethyl-phenyl
F
Table B: Compounds of formula (lb'):
Figure imgf000020_0001
Figure imgf000021_0001
dimethyl-phenyl
Table C: Compounds of formula (Ic'):
Figure imgf000021_0002
Figure imgf000022_0001
Figure imgf000023_0001
Figure imgf000024_0001
dimethyl-phenyl
Table D: Compounds of formula (lb"):
Figure imgf000024_0002
Figure imgf000025_0001
Figure imgf000026_0001
F dimethyl-phenyl
Table E: Compounds of formula (Ic"):
Figure imgf000026_0002
Figure imgf000027_0001
Figure imgf000028_0001
Table F: Compounds of formula (Ic'"):
Figure imgf000029_0001
Figure imgf000030_0001
Figure imgf000031_0001
F dimethyl-phenyl
Table G: Compounds of formula (Ic""):
Figure imgf000031_0002
Figure imgf000032_0001
Figure imgf000033_0001
Figure imgf000034_0001
dimethyl-phenyl
In an embodiment (B), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I
Figure imgf000034_0002
wherein
A , A , A and A are independently of one another C-X-R , C-R or nitrogen, provided that
1 2 3 4 3 1 2 3 4 at least one of A , A , A and A is C-X-R and no more than two of A , A , A and A are nitrogen;
R1 and R2 are independently of one another hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl;
G1 and G2 are independently of one another oxygen or sulfur;
each R3 is independently hydrogen, Ci-Ci2alkyl, Ci-Ci2haloalkyl, C2-Csalkenyl, C2-
C8alkynyl, aryl or aryl substituted by halogen or Ci-C4alkyl, or heterocyclyl or heterocyclyl substituted by halogen or Ci-C4alkyl;
each X is independently oxygen, sulfur or N-R4; wherein
each R4 is independently hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl;
each R5 is independently hydrogen, halogen, Ci-C4alkyl or trifluoromethyl;
Q1 is aryl or aryl substituted by one to five substituents R6, which may be the same or different, or Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R6, which may be the same or different; wherein each R6 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2- C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3- C6halocycloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci- C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, Ci- C4alkylamino, di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci- C4alkoxycarbonyl, Ci-C4alkylcarbonylamino or phenyl; and
Q2 is a moiety of formula (II) or (III)
Figure imgf000035_0001
wherein
Y! and Y5 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci- C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, d- C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y3 is C2-C6perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C6perfluoroalkylsulfinyl or Ci-C6per- fluoroalkylsulfonyl;
Y2 and Y4 are independently of each other hydrogen, halogen or Ci-C4alkyl;
Y6 and Y9 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci- C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, d- C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y8 is Ci-C4haloalkoxy, C2-C6perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C6perfluoroalkyl- sulfinyl or Ci-Ceperfluoroalkylsulfonyl;
Y7 is hydrogen, halogen or Ci-C4alkyl;
or salts or N-oxides thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (B) Preferred values of A1, A2, A3, A4, R1, R2, G1, G2, R3, X, R4, R5, Q1, R6, Q2, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are, in any combination, as set out below.
Preferably A1 is C-X-R3 or C-R5. Preferably A2 is C-X-R3 or C-R5.
Preferably A3 is C-X-R3 or C-R5.
Preferably A4 is C-X-R3 or C-R5.
Preferably one, two or three of A1, A2, A3 and A4 are C-X-R3.
More preferably one or two of A1, A2, A3 and A4 are C-X-R3.
Most preferably one of A1, A2, A3 and A4 is C-X-R3.
Preferably R1 is hydrogen, methyl, ethyl or acetyl.
More preferably R1 is hydrogen, methyl or ethyl.
Even more preferably R1 is hydrogen or ethyl.
Most preferably R1 is hydrogen.
Preferably R2 is hydrogen, methyl, ethyl or acetyl.
More preferably R2 is hydrogen, methyl or ethyl.
Even more preferably R2 is hydrogen or ethyl.
Most preferably R2 is hydrogen.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably each R3 is independently hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, C2- C4alkenyl, C2-C4alkynyl, phenyl or phenyl substituted by one to three substituents independently selected from halogen or Ci-C4alkyl.
More preferably each R3 is independently hydrogen, methyl, ethyl, n-propyl, allyl, phenyl or phenyl mono-substituted by halogen or methyl.
Even more preferably each R3 is independently hydrogen, methyl or ethyl.
Most preferably each R3 is independently hydrogen or methyl.
Preferably each X is independently oxygen or sulfur.
Most preferably each X is oxygen.
Preferably each R4 is independently hydrogen or methyl.
Preferably each R5 is independently hydrogen, fluoro, methyl or trifluoromethyl. More preferably each R5 is independently hydrogen or fluoro.
Most preferably each R5 is hydrogen.
Preferably Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of such groups for Q1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3- yl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro- pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5-trifluoromethyl-pyrid-2- yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 1 ,3 -dimethyl -pyrazol-5-yl, 4- fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2-fluoro-3-trifluoromethyl-phenyl, 2-methyl-phenyl, 3- methyl-pyrid-2-yl, 2-methylthio-pyrid-3-yl, 4-nitro-phenyl, phenyl, l ,2,3-thiadiazol-4-yl and thiophen-2-yl.
More preferably Q1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of such preferred groups for Q1 are 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro- pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-pyrid-3- yl, 2-fluoro-3 -trifluoromethyl -phenyl, 2-methyl-phenyl, 3-methyl-pyrid-2-yl, 2-methylthio- pyrid-3 -yl and phenyl.
Even more preferably Q1 is phenyl substituted by one substituent selected from cyano, fluoro or chloro. Examples of even more preferred groups for Q1 are 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano-phenyl and 4-fluoro-phenyl.
Most preferably Q1 is 4-fluoro-phenyl.
Each R6 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl,
Ci-C3alkoxy, Ci-Cshaloalkoxy, Ci-C3alkylthio, Ci-Cshaloalkylthio, Ci-C4alkylamino or di- (C i -C4alkyl)-amino .
A particularly preferred group of compounds are compounds of formula (I) wherein Q1 is aryl or aryl substituted by one to five substituents R6, which may be the same or different.
Preferably Q1 is phenyl or phenyl substituted by one to three substituents
independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of such groups for Q1 are 2-bromo-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3- chloro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2- fluoro-3-trifluoromethyl-phenyl, 2-methyl-phenyl, 4-nitro-phenyl and phenyl.
More preferably Q1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of such preferred groups for Q1 are 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano-phenyl, 2,5- dichloro-phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3-trifluoromethyl-phenyl, 2- methyl-phenyl and phenyl.
Another particularly preferred group of compounds are compounds of formula (I) wherein Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R6, which may be the same or different. The heterocyclyl group is preferably a heteroaryl group.
Preferably Q1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of such groups for Q1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2-chloro-pyrid- 3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5- trifluoromethyl-pyrid-2-yl, l,3-dimethyl-pyrazol-5-yl, 2-fluoro-pyrid-3-yl, 3-methyl-pyrid-2- yl, 2-methylthio-pyrid-3-yl, l,2,3-thiadiazol-4-yl and thiophen-2-yl.
More preferably Q1 is pyridyl or pyridyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of such preferred groups for Q1 are 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid- 3-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 2-fluoro-pyrid-3-yl, 3-methyl-pyrid-2-yl and 2- methylthio-pyrid-3 -yl.
Preferably Q2 is a moiety of formula (II). Especially preferred groups for Q2 are 4- heptafluoroisopropyl-2,6-dimethyl-phenyl, 4-heptafluoroisopropyl-2,6-diethyl-phenyl and 4- heptafluoroisopropyl -2 -methoxymethyl-6-methyl -phenyl.
Preferably Y1 is cyano, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl.
More preferably Y1 is cyano, chloro, methyl or trifluoromethyl.
Even more preferably Y1 is methyl or ethyl.
Most preferably Y1 is methyl.
Preferably Y2 is hydrogen, fluoro, chloro or methyl.
Most preferably Y2 is hydrogen.
Preferably Y3 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl. Most preferably Y3 is heptafiuoroprop-2-yl.
Preferably Y4 is hydrogen, fluoro, chloro or methyl.
Most preferably Y4 is hydrogen.
Preferably Y5 is cyano, chloro, methyl, ethyl or trifluoromethyl.
More preferably Y5 is cyano, chloro, methyl or trifluoromethyl.
Even more preferably Y5 is methyl or ethyl.
Most preferably Y5 is methyl.
Preferably Y6 is cyano, chloro, methyl, ethyl or trifluoromethyl.
More preferably Y6 is methyl or ethyl.
Most preferably Y6 is methyl.
Preferably Y7 is hydrogen, fluoro, chloro or methyl.
Most preferably Y7 is hydrogen.
Preferably Y8 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio,
heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
Most preferably Y8 is heptafluoroprop-2-yl.
Preferably Y9 is cyano, chloro, methyl, ethyl or trifluoromethyl.
More preferably Y9 is methyl or ethyl.
Most preferably Y9 is methyl.
In one embodiment of the invention Y1 and Y5 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkylthio, Ci-Cshaloalkylthio, Ci-C3alkylsulfinyl, Ci-Cshaloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl.
In one embodiment of the invention Y6 and Y9 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl. embodiment the invention provides a novel compound of formula (la)
Figure imgf000040_0001
wherein A1, A2, A3, A4, R1, R2, G1, G2, Q1, Y1, Y2, Y3, Y4 and Y5 are as defined in relation to
1 2 3 4 1 2 1 2 formula I; or salts or N-oxides thereof. The preferences forA,A,A,A,R,R,G,G, Q1, Y1, Y2, Y3, Y4andY5 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
In another embodiment of the embodiment (B) the invention provides a novel compound of formula (lb)
Figure imgf000040_0002
wherein A1, A2, A3, A4, R1, R2, G1, G2, Q1, Y6, Y7, Y8 and Y9 are as defined in relation to
1 2 3 4 1 2 1 2 formula I; or salts or N-oxides thereof. The preferences forA,A,A,A,R,R,G,G, Q1, Y6, Y7, Y8 andY9 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
In yet another embodiment of the embodiment (B) the invention provides a novel compound of formula (Ic):
Figure imgf000041_0001
wherein A 1 , 1
Figure imgf000041_0002
Q1 and Q 2z are as defined in relation to formula I, and each X is independently oxygen or sulfur; or salts or N-oxides thereof. The preferences for A1, A2, A3, A4, R1, R2, G1, G2, Q1 and Q2 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I).
In a further embodiment the invention provides a novel compound of formula (Ic) wherein A 1 ,
Figure imgf000041_0003
Q11 and Q 2z are as defined in relation to formula I, and each X is oxygen; or salts or N-oxides thereof. The preferences for A1, A2, A3, A4, R1, R2, G1, G2, Q1 and Q2 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I). A group of particularly preferred compounds are compounds of formula (Ic) wherein X1, X3 and X4 are hydrogen and X2 is hydroxy. A further group of particularly preferred compounds are compounds of formula (Ic) wherein X1, X2 and X3 are hydrogen and X4 is hydroxy. Another group of particularly preferred compounds are compounds of formula (Ic) wherein X1, X2 and X3 are hydrogen and X4 is allyloxy. A further group of particularly preferred compounds are compounds of formula (Ic) wherein X1 and X3 are both hydrogen and X2 and X4 are both hydroxy.
In yet a further embodiment the present invention provides a novel compound of formula (Ic) wherein A1, A2, A3, A4, R1, R2, G1, G2, Q1 and Q2 are as defined in relation to formula I, and each X is sulfur; or salts or N-oxides thereof. The preferences for A1, A2, A3,
4 1 2 1 2 1 2
A , R , R , G , G , Q and Q are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I). A group of particularly preferred compounds are compounds of formula (Ic) wherein X2, X3 and X4 are hydrogen and X1 is methylthio.
In another embodiment of the embodiment (B) the invention provides a novel
1 2 3 4 1 2 1 2 1 2
compound of formula (Ic) wherein A , A , A , A , R , R , G , G , Q and Q are as defined in relation to formula I, and each X is N-R4 wherein R4 is as defined in relation to formula I; or salts or N-oxides thereof. The preferences for A1, A2, A3, A4, R1, R2, G1, G2, Q1 and Q2 are the same as the preferences set out for the corresponding substituents of the compounds of the formula (I). A group of particularly preferred compounds are compounds of formula (Ic) wherein X2, X3 and X4 are hydrogen and X1 is Ν,Ν-dimethylamino. A further group of particularly preferred compounds are compounds of formula (Ic) wherein X1, X2 and X4 are hydrogen and X3 is Ν,Ν-dimethylamino. Another group of particularly preferred compounds are compounds of formula (Ic) wherein X2, X3 and X4 are hydrogen and X1 is N-ethylamino. A further group of particularly preferred compounds are compounds of formula (Ic) wherein X1, X2 and X4 are hydrogen and X3 is N-ethylamino.
The compounds in Tables 1 to 25 below illustrate the compounds of the embodiment (B) of the invention.
Table 1 :
Table 1 provides 119 compounds of formula (If) wherein Q1 is 5-bromo-furan-2-yl.
Figure imgf000042_0001
Compound X1 X2 X3 X4
number
1.001 HO- H H H
1.002 H HO- H H
1.003 H H HO- H
1.004 H H H HO-
1.005 MeO- H H H
1.006 H MeO- H H
1.007 H H MeO- H
1.008 H H H MeO-
1.009 MeO- H H MeO-
1.010 H MeO- H MeO-
1.011 H H MeO- MeO- Compound X1 X2 XJ X4 number
1.012 PhO- H H H
1.013 H PhO- H H
1.014 H H PhO- H
1.015 H H H PhO-
1.016 m-Me- H H H
PhO-
1.017 H m-Me- H H
PhO-
1.018 H H m-Me- H
PhO-
1.019 H H H m-Me- PhO-
1.020 p-Cl- H H H
PhO-
1.021 H p-Cl- H H
PhO-
1.022 H H p-Cl- H
PhO-
1.023 H H H p-Cl- PhO-
1.024 HO- F H H
1.025 HO- H F H
1.026 HO- H H F
1.027 F HO- H H
1.028 H HO- F H
1.029 H HO- H F
1.030 F H HO- H
1.031 H F HO- H
1.032 H H HO- F
1.033 F H H HO- Compound X1 X2 XJ X4 number
1.034 H F H HO-
1.035 H H F HO-
1.036 MeO- F H H
1.037 MeO- H F H
1.038 MeO- H H F
1.039 F MeO- H H
1.040 H MeO- F H
1.041 H MeO- H F
1.042 F H MeO- H
1.043 H F MeO- H
1.044 H H MeO- F
1.045 F H H MeO-
1.046 H F H MeO-
1.047 H H F MeO-
1.048 PhO- F H H
1.049 PhO- H F H
1.050 PhO- H H F
1.051 F PhO- H H
1.052 H PhO- F H
1.053 H PhO- H F
1.054 F H PhO- H
1.055 H F PhO- H
1.056 H H PhO- F
1.057 F H H PhO-
1.058 H F H PhO-
1.059 H H F PhO-
1.060 MeS- H H H
1.061 H MeS- H H
1.062 H H MeS- H Compound X1 X2 XJ X4 number
1.063 H H H MeS-
1.064 PhS- H H H
1.065 H PhS- H H
1.066 H H PhS- H
1.067 H H H PhS-
1.068 p-Me- H H H
PhS-
1.069 H p-Me- H H
PhS-
1.070 H H p-Me- H
PhS-
1.071 H H H p-Me- PhS-
1.072 m-F-PhS- H H H
1.073 H m-F-PhS- H H
1.074 H H m-F-PhS- H
1.075 H H H m-F-PhS-
1.076 MeS- F H H
1.077 MeS- H F H
1.078 MeS- H H F
1.079 F MeS- H H
1.080 H MeS- F H
1.081 H MeS- H F
1.082 F H MeS- H
1.083 H F MeS- H
1.084 H H MeS- F
1.085 F H H MeS-
1.086 H F H MeS-
1.087 H H F MeS-
1.088 PhS- F H H Compound X1 X2 XJ X4 number
1.089 PhS- H F H
1.090 PhS- H H F
1.091 F PhS- H H
1.092 H PhS- F H
1.093 H PhS- H F
1.094 F H PhS- H
1.095 H F PhS- H
1.096 H H PhS- F
1.097 F H H PhS-
1.098 H F H PhS-
1.099 H H F PhS-
1.100 EtHN- H H H
1.101 H EtHN- H H
1.102 H H EtHN- H
1.103 H H H EtHN-
1.104 Me2N- H H H
1.105 H Me2N- H H
1.106 H H Me2N- H
1.107 H H H Me2N-
1.108 PhHN- H H H
1.109 H PhHN- H H
1.110 H H PhHN- H
1.111 H H H PhHN-
1.112 m-Me- H H H
PhHN-
1.113 H m-Me- H H
PhHN-
1.114 H H m-Me- H
PhHN- Compound X1 X2 X3 X4
number
1.115 H H H m-Me- PhHN-
1.116 p-F- H H H
PhHN-
1.117 H p-F- H H
PhHN-
1.118 H H p-F- H
PhHN-
1.119 H H H p-F- PhHN-
Table 2:
Table 2 provides 119 compounds of formula (If) wherein Q1 is 2-bromo-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 3:
Table 3 provides 119 compounds of formula (If) wherein Q1 is 5-bromo-pyrid-3-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 4:
Table 4 provides 119 compounds of formula (If) wherein Q1 is 2-chloro-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 5:
Table 5 provides 119 compounds of formula (If) wherein Q1 is 3-chloro-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 6:
Table 6 provides 119 compounds of formula (If) wherein Q1 is 2-chloro-pyrid-3-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 7:
Table 7 provides 119 compounds of formula (If) wherein Q1 is 2-chloro-pyrid-4-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 8: Table 8 provides 119 compounds of formula (If) wherein Q1 is 6-chloro-pyrid-3-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 9:
Table 9 provides 119 compounds of formula (If) wherein Q1 is 5-chloro-thiophen-2-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 10:
Table 10 provides 119 compounds of formula (If) wherein Q1 is 3-chloro-5-trifluoromethyl- pyrid-2-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 11 :
Table 11 provides 119 compounds of formula (If) wherein Q1 is 4-cyano-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 12:
Table 12 provides 119 compounds of formula (If) wherein Q1 is 2,5-dichloro-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 13:
Table 13 provides 119 compounds of formula (If) wherein Q1 is 2,3-difluoro-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 14:
Table 14 provides 119 compounds of formula (If) wherein Q1 is l,3-dimethyl-pyrazol-5-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 15:
Table 15 provides 119 compounds of formula (If) wherein Q1 is 4-fluoro-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 16:
Table 16 provides 119 compounds of formula (If) wherein Q1 is 2-fluoro-pyrid-3-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 17:
Table 17 provides 119 compounds of formula (If) wherein Q1 is 2-fluoro-3-trifluoromethyl- phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 18:
Table 18 provides 119 compounds of formula (If) wherein Q1 is 2 -methyl -phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 19: Table 19 provides 119 compounds of formula (If) wherein Q1 is 3 -methyl -pyrid-2-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 20:
Table 20 provides 119 compounds of formula (If) wherein Q1 is 2-methylthio-pyrid-3-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 21 :
Table 21 provides 119 compounds of formula (If) wherein Q1 is 4-nitro-phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 22:
Table 22 provides 119 compounds of formula (If) wherein Q1 is phenyl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 23:
Table 23 provides 119 compounds of formula (If) wherein Q1 is l,2,3-thiadiazol-4-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 24:
Table 24 provides 119 compounds of formula (If) wherein Q1 is thiophen-2-yl and X1, X2, X3 and X4 have the values listed in Table 1.
Table 25:
Table 25 provides 119 compounds of formula (If) wherein Q1 is 2-chloro-5-nitro-phenyl and X1 , X2, X3 and X4 have the values listed in Table 1.
Preferred compounds of the embodiment (B) are
5-(3-chloro-benzoylamino)-N-[2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)- phenyl] -2-phenoxy-benzamide;
N-[2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)-phenyl]-3-(4-fluoro- benzoylamino)-2,6-dimethoxy-benzamide;
5-(4-cyano-benzoylamino)-N-[2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)- phenyl] -2-ethylamino-benzamide;
Preparation of 3-(4-Cyano-benzoylamino)-4-dimethylamino-N-[2,6-dimethyl-4-(l ,2,2,2- tetrafluoro- 1 -trifluoromethyl-ethyl)-phenyl]-benzamide;
Or a compound according to the Table A and Table D: Table A: Compounds of formula (If):
Figure imgf000050_0001
X1 X1 X4 X4
Figure imgf000050_0002
No.
Al 3-chloro- H H PhO- H phenyl
A2 3-chloro- MeS- H H H phenyl
A3 3-chloro- H H PhS- H phenyl
A4 3-chloro- H H p-Me- H phenyl PhS-
A5 3-chloro- m- H H H phenyl Me-
PhO-
A6 3-chloro- p-Cl- H H H phenyl PhO-
A7 4-cyano- H H H HO- phenyl
A8 4-cyano- H H H allyl- phenyl 0-
A9 4-fluoro- H MeO- H MeO- phenyl
A10 4-fluoro- MeO- H H H phenyl
Figure imgf000051_0001
Figure imgf000052_0001
Figure imgf000053_0001
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
phenyl
Table D: Compounds of formula (Ij):
Figure imgf000058_0002
In an embodiment (C), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000059_0001
wherein
A1, A2, A3 and A4 are independently of one another C-X or nitrogen, provided that no more than two of A1, A2, A3 and A4 are nitrogen;
each X is independently hydrogen, halogen, Ci-C4alkyl, Ci-C4haloalkyl or Ci-C4alkoxy; R1 and R2 are independently of one another hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl; G1 and G2 are independently of one another oxygen or sulfur;
Q1 is aryl or aryl substituted by one to five substituents R5, which may be the same or different, or Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R5, which may be the same or different;
R3 is hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, C3-C6cycloalkyl-Ci-C4-alkyl-, Ci-C4alkoxy-Ci- C4-alkyl-, Ci-C4haloalkoxy-Ci-C4-alkyl-, Ci-C4alkylthio-Ci-C4-alkyl-, Ci-C4haloalkylthio- Ci-C4-alkyl-, C3-Cscycloalkyl, C3-Cshalocycloalkyl, phenyl or phenyl substituted by one to five substituents R5, which may be the same or different, 2-naphthyl or 2-naphthyl substituted by one to five substituents R5, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R5, which may be the same or different;
R4 is hydrogen, halogen, cyano, Ci-C6alkyl, Ci-C6haloalkyl, C3-C6cycloalkyl-Ci-C4-alkyl-, Ci-C4alkoxy-Ci-C4-alkyl-, Ci-C4haloalkoxy-Ci-C4-alkyl-, Ci-C4alkylthio-Ci-C4-alkyl-, d- C4haloalkylthio-C i -C4-alkyl-, C i -C4alkylsulfinyl-C i -C4-alkyl-, C i -C4haloalkylsulfinyl-C i - C4alkyl-, Ci-C4-alkylsulfonyl-Ci-C4-alkyl-, Ci-C4haloalkylsulfonyl-Ci-C4-alkyl-, C3- Cscycloalkyl, C3-Cshalocycloalkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, Ci-C6alkylthio, Ci- C6haloalkylthio, Ci-C6alkylsulfinyl, Ci-C6haloalkylsulfinyl, Ci-C6alkylsulfonyl, Ci- Ce aloalkylsulfonyl, N,N-di(Ci-C6)alkylamino, phenyl or phenyl substituted by one to five substituents R5, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R5, which may be the same or different;
Y1 and Y4 are independently of each other hydrogen, cyano, halogen, Ci-C4alkyl, Ci- C4haloalkyl, Ci-C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-
C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl; Y2 and Y3 are independently of each other hydrogen, halogen or Ci-C4alkyl; and each R5 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2- C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-C6halo- cycloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkyl- sulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, Ci-C4alkyl- amino, di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxy- carbonyl, Ci-C4alkylcarbonylamino or phenyl;
or salts or N-oxides thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (C) preferred values of A1, A2, A3, A4, X, R1, R2, G1, G2, Q1, R3, R4, Y1, Y2, Y3 and Y4 are, in any combination, as set out below.
Preferably A1 is C-X.
Preferably A2 is C-X.
Preferably A3 is C-X.
Preferably A4 is C-X.
Preferably each X is independently hydrogen, fluoro, chloro, bromo, methyl, trifiuoromethyl or methoxy.
More preferably each X is independently hydrogen, fluoro, chloro, bromo, methyl or trifiuoromethyl.
Even more preferably each X is independently hydrogen, fluoro, methyl or trifiuoromethyl.
Yet even more preferably each X is independently hydrogen or fluoro.
Most preferably each X is hydrogen.
Preferably R1 is hydrogen, methyl, ethyl or acetyl.
More preferably R1 is hydrogen, methyl or ethyl. Even more preferably R1 is hydrogen or ethyl.
Most preferably R1 is hydrogen.
Preferably R2 is hydrogen, methyl, ethyl or acetyl.
More preferably R2 is hydrogen, methyl or ethyl.
Even more preferably R2 is hydrogen or ethyl.
Most preferably R2 is hydrogen.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of such groups for Q1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3- yl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro- pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5-trifluoromethyl-pyrid-2- yl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, l ,3-dimethyl-lH-pyrazol-5-yl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2-fluoro-3-trifluoromethyl-phenyl, 2-methyl-phenyl, 3- methyl-pyrid-2-yl, 2-methylthio-pyrid-3-yl, 4-nitro-phenyl, phenyl, l ,2,3-thiadiazol-4-yl, thiophen-2-yl and 4-trifluoromethyl-phenyl.
More preferably Q1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of more preferred groups for Q1 are 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl,
2- chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano- phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2- fluoro-3-trifluoromethyl-phenyl, 2-methyl-phenyl, 3-methyl-pyrid-2-yl, 2-methylthio-pyrid-
3- yl, phenyl and 4-trifluoromethyl-phenyl.
Even more preferably Q1 is phenyl substituted by one substituent selected from cyano, fluoro or chloro. Examples of even more preferred groups for Q1 are 2-chloro-phenyl, 3-chloro-phenyl, 4-cyano-phenyl and 4-fluoro-phenyl.
Most preferably Q1 is 4-fluoro-phenyl.
Preferably R3 is Ci-C6alkyl, Ci-C6haloalkyl, phenyl or phenyl substituted by one to five substituents R5, which may be the same or different. More preferably R3 is Ci-C6alkyl or Ci-Cehaloalkyl.
Most preferably R3 is trifluoromethyl.
Preferably R4 is Ci-C6alkyl, Ci-C6haloalkyl, phenyl or phenyl substituted by one to five substituents R5, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R5, which may be the same or different.
More preferably R4 is phenyl or phenyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-C3haloalkoxy, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-C3halo- alkoxy, which may be the same or different.
Even more preferably R4 is phenyl or phenyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-C3haloalkoxy, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-C3halo- alkoxy, which may be the same or different. Examples of such groups for R4 are 4-bromo- phenyl, 4-chloro-phenyl, 4-cyano-phenyl, 3,4-dichloro-phenyl, 4-dif uoromethoxy-phenyl, 4- fluoro-phenyl, 4-methylsulfonyloxy-phenyl, 4-methylsulfonyl-phenyl, 4-methylthio-phenyl, 4-nitro-phenyl, phenyl, 4-trifluoromethoxy-phenyl and 4-trifluoromethyl-phenyl.
Most preferably R4 is phenyl or phenyl substituted by one substituent selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl. Examples of such preferred groups for R4 are 4-chloro- phenyl, 4-fluoro-phenyl and 4-trifluoromethyl-phenyl.
Preferably Y1 is cyano, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl.
More preferably Y1 is cyano, chloro, methyl or trifluoromethyl.
Even more preferably Y1 is methyl or ethyl.
Most preferably Y1 is methyl.
Preferably Y2 is hydrogen, fluoro, chloro or methyl.
Most preferably Y2 is hydrogen.
Preferably Y3 is hydrogen, fluoro, chloro or methyl.
Most preferably Y3 is hydrogen.
Preferably Y4 is cyano, chloro, methyl, ethyl or trifluoromethyl.
More preferably Y4 is cyano, chloro, methyl or trifluoromethyl.
Even more preferably Y4 is methyl or ethyl.
Most preferably Y4 is methyl. One preferred embodiment of the embodiment (C) are compounds of formula (la) wherein A1, A2, A3, A4 are CH.
Another preferred embodiment of the embodiment (C) are compounds of formula (lb) wherein A1 is C-F, and A2, A3, and A4 are CH.
A further preferred embodiment of the embodiment (C) are compounds of formula
(Ic) wherein A3 is C-F, and A1, A2, and A4 are CH.
Yet another preferred embodiment of the embodiment (C) are compounds of formula (Id) wherein A4 is C-F, and A1, A2, and A3 are CH.
One preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- dimethy 1-pheny 1.
Another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2-ethyl-6- methy 1-pheny 1.
A further preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- diethy 1-pheny 1.
Yet another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2- methoxymethyl-6-methyl-phenyl.
One preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- dimethy 1-pheny 1.
Another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2-ethyl-6- methy 1-pheny 1.
A further preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- diethy 1-pheny 1.
Yet another preferred embodiment of the embodiment (C) are compounds of formula
(I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2- methoxymethyl-6-methyl -phenyl. One preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2,6-dimethyl-phenyl.
Another preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2-ethyl-6-methyl-phenyl.
A further preferred embodiment of the embodiment (C) are compounds of formula (I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2,6-diethyl-phenyl.
Yet another preferred embodiment of the embodiment (C) are compounds of formula
(I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5- yl]-2-methoxymethyl-6-methyl-phenyl.
In one embodiment of the invention Y1 and Y4 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkylthio, Ci-Cshaloalkylthio, Ci-Csalkylsulfinyl, Ci-Cshaloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-Cshaloalkylsulfonyl. The preferences for
Y1 and Y4 are the same as set out for compounds of formula (I) except that Y1 and Y4 cannot be methoxymethyl.
The compounds in the following Tables 1 to 22 below illustrate the compounds according to the embodiment (C) of the invention.
Table 1 :
Table 1 provides 26 compounds of formula (la) wherein R4 is 4-bromo-phenyl and Q1 has the values listed in the table below.
Figure imgf000064_0001
Compound numbers Q
1.02 2-bromo-phenyl
1.03 5 -bromo -pyrid-3 -yl
1.04 2-chloro-5 -nitro-phenyl
1.05 2-chloro-phenyl
1.06 3-chloro-phenyl
1.07 2-chloro-pyrid-3 -yl
1.08 2-chloro-pyrid-4-yl
1.09 6-chloro-pyrid-3 -yl
1.10 5-chloro-thiophen-2-yl
1.11 3 -chloro-5 -trifluoromethyl-pyrid-2- yl
1.12 4-cyano-phenyl
1.13 2,5-dichloro-phenyl
1.14 2,3-difluoro-phenyl
1.15 1 ,3-dimethyl-lH-pyrazol-5-yl
1.16 4-fluoro-phenyl
1.17 2-fluoro-pyrid-3 -yl
1.18 2-fluoro-3 -trifiuoromethyl -phenyl
1.19 2-methyl -phenyl
1.20 3 -methyl -pyrid-2-yl
1.21 2-methylthio-pyrid-3-yl
1.22 4-nitro-phenyl
1.23 phenyl
1.24 1 ,2,3-thiadiazol-4-yl
1.25 thiophen-2-yl
1.26 4-trifluoromethyl-phenyl
Table 2:
Table 2 provides 26 compounds of formula (la) wherein R4 is 4-chloro-phenyl and Q1 has the values listed in Table 1. Table 3:
Table 3 provides 26 compounds of formula (la) wherein R4 is 4-cyano-phenyl and Q1 has the values listed in Table 1.
Table 4:
Table 4 provides 26 compounds of formula (la) wherein R4 is 3,4-dichloro-phenyl and Q1 has the values listed in Table 1.
Table 5:
Table 5 provides 26 compounds of formula (la) wherein R4 is 4-difluoromethoxy-phenyl and Q1 has the values listed in Table 1.
Table 6:
Table 6 provides 26 compounds of formula (la) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 7:
Table 7 provides 26 compounds of formula (la) wherein R4 is 4-methylsulfonyloxy-phenyl and Q1 has the values listed in Table 1.
Table 8:
Table 8 provides 26 compounds of formula (la) wherein R4 is 4-methylsulfonyl-phenyl and Q1 has the values listed in Table 1.
Table 9:
Table 9 provides 26 compounds of formula (la) wherein R4 is 4-methylthio-phenyl and Q1 has the values listed in Table 1.
Table 10:
Table 10 provides 26 compounds of formula (la) wherein R4 is 4-nitro-phenyl and Q1 has the values listed in Table 1.
Table 11 :
Table 11 provides 26 compounds of formula (la) wherein R4 is phenyl and Q1 has the values listed in Table 1.
Table 12:
Table 12 provides 26 compounds of formula (la) wherein R4 is 4-trifluoromethoxy-phenyl and Q1 has the values listed in Table 1.
Table 13:
Table 13 provides 26 compounds of formula (la) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1. Table 14:
Table 14 provides 26 compounds of formula (lb) wherein R4 is 4-chloro-phenyl and Q1 has the values listed in Table 1.
Figure imgf000067_0001
Table 15:
Table 15 provides 26 compounds of formula (lb) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 16:
Table 16 provides 26 compounds of formula (lb) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1.
Table 17:
Table 17 provides 26 compounds of formula (Ic) wherein R4 is 4-chloro-phenyl and Q1 has the values listed in Table 1.
Figure imgf000067_0002
Table 18:
Table 18 provides 26 compounds of formula (Ic) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 19:
Table 19 provides 26 compounds of formula (Ic) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1.
Table 20:
Table 20 provides 26 compounds of formula (Id) wherein R4 is 4-chloro-phenyl and Q1 has he values listed in Table 1.
Figure imgf000068_0001
Table 21 :
Table 21 provides 26 compounds of formula (Id) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 22:
Table 22 provides 26 compounds of formula (Id) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1.
Preferred compounds of the emboduiment (C) are
2 -methyl -benzoic acid 3- (4-r3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihvdro-isoxazol-5- vH-2,6-dimethyl-phenylcarbamoyl| -phenyl amide (Compound A3 of Table A)
N-(4-r3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihvdro-isoxazol-5-yl1-2,6-dimethyl- phenyll -3-nitrobenzamide
4-trifluoromethyl -benzoic acid 3-(4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro- isoxazol-5-yl1-2,6-dimethyl-phenylcarbamoyl| -phenyl amide (Compound A30 of Table A) Or a compound as described in Table A: Compounds of formula (la):
Figure imgf000068_0002
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
In an embodiment (D), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000071_0002
wherein
A1, A2, A3 and A4 are independently of one another C-X or nitrogen, provided that no more than two of A1, A2, A3 and A4 are nitrogen;
each X is independently hydrogen, halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl or Ci- C4alkoxy;
R1 and R2 are independently of one another hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl; G1 and G2 are independently of one another oxygen or sulfur;
Q1 is aryl or aryl substituted by one to five substituents R3, which may be the same or different, or Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R3, which may be the same or different; wherein
each R3 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2- C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-C6halo- cycloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkyl- sulfinyl,
Figure imgf000072_0001
Ci-C3alkylsulfonyl, Ci-Cshaloalkylsulfonyl, amino, Ci- C4alkylamino, di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, C\- C4alkoxycarbonyl, Ci-C4alkylcarbonylamino, aryl which is optionally substituted by one to three substituents independently selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci- C4alkoxy or Ci-C4haloalkoxy, or heteroaryl which is optionally substituted by one to three substituents independently selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy or Ci-C4haloalkoxy; and
Q2 is a moiety of formula (II) or (III)
Figure imgf000072_0002
wherein
Y1 and Y5 are independently of each other hydrogen, cyano, halogen, Ci-C4alkyl, Ci-C4halo- alkyl, Ci-C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, d- C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y3 is C2-C6perfiuoroalkyl, Ci-C6perfluoroalkylthio, Ci-C6perfluoroalkylsulfinyl or Ci-C6per- fluoroalkylsulfonyl;
Y2 and Y4 are independently of each other hydrogen, halogen or Ci-C4alkyl;
Y6 and Y9 are independently of each other hydrogen, cyano, halogen, Ci-C4alkyl, Ci-C4halo- alkyl, Ci-C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, d- C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y8 is Ci-C4haloalkoxy, C2-C6perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C6perfluoroalkyl- sulfinyl or Ci-C6perfluoroalkylsulfonyl;
Y7 is hydrogen, halogen or Ci-C4alkyl;
or salts or N-oxides thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (D) the preferred values of A1, A2, A3, A4, X, R1, R2, G1, G2, Q1, Q2, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are, in any combination, as set out below.
Preferably A1 is C-X. Preferably A2 is C-X.
Preferably A3 is C-X.
Preferably A4 is C-X.
Preferably each X is independently hydrogen, fluoro, chloro, bromo, cyano, methyl, trifluoromethyl or methoxy.
More preferably each X is independently hydrogen, fluoro, chloro, bromo, cyano, methyl or trifluoromethyl.
Even more preferably each X is independently hydrogen, fluoro, methyl or trifluoromethyl.
Yet even more preferably each X is independently hydrogen or fluoro.
Most preferably each X is hydrogen.
Preferably R1 is hydrogen, methyl, ethyl or acetyl.
More preferably R1 is hydrogen, methyl or ethyl.
Even more preferably R1 is hydrogen or ethyl.
Most preferably R1 is hydrogen.
Preferably R2 is hydrogen, methyl, ethyl or acetyl.
More preferably R2 is hydrogen, methyl or ethyl.
Even more preferably R2 is hydrogen or ethyl.
Most preferably R2 is hydrogen.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably Q1 is phenyl, pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl, or phenyl, pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methyl- sulfmyl, methylsulfonyl or phenyl. Examples of preferred groups for Q1 are biphenyl-4-yl, 5- bromo-furan-2-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 3- chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2- methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3- yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-2,4,5-trifluoro- phenyl, 3 -chloro-5 -trifluoromethyl -pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-dif uoro-phenyl, 2,5-dimethyl-2H-pyrazol-3-yl, 3-fluoro-4- hydroxy-phenyl, 2-fluoro-4-nitro-phenyl, 3-fluoro-4-nitro-phenyl, 2-fluoro-phenyl, 3 -fluorophenyl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 3-fluoro-pyrid-4-yl, 2-fluoro-3-trifluoromethyl phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 4-fluoro-3-trifluoromethyl-phenyl, furan-2-yl, lH-imidazol-4-yl, 2-methoxy-phenyl, 4-methoxy-phenyl, 4-methoxy-thiophen-3-yl, 2- methyl-phenyl, 3 -methyl -phenyl, 4-methyl-phenyl, 5-methyl-3-phenyl-isoxazol-4-yl, 5- methyl-1 -phenyl- lH-pyrazol-4-yl, 4-methyl-2-phenyl-pyrimid-5-yl, 4-methyl-2-phenyl- thiazol-5-yl, 3-methyl-pyrid-2-yl, 4-methyl-l,2,3-thiadiazol-5-yl, 4-methylthio-phenyl, 2- methylthio-pyrid-3-yl, 2-methylthio-4-trifluoromethyl -phenyl, l-methyl-3 -trifluoromethyl - lH-pyrazol-4-yl, l-methyl-3-trifluoromethyl-lH-pyrrol-4-yl, 2-nitro-phenyl, 3-nitro-phenyl,
4- nitro-phenyl, phenyl, 5-phenyl-furan-2-yl, 5-phenyl-oxazol-4-yl, pyrid-3-yl, pyrid-4-yl, l,2,3-thiadiazol-4-yl, l,2,5-trimethyl-lH-pyrrol-3-yl, thiophen-2-yl, 2-trifluoromethyl- phenyl and 4-trifluoromethyl-phenyl.
More preferably Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of more preferred groups for Q1 are biphenyl-4-yl, 5- bromo-furan-2-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 3- chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2- methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3 yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro-5-trifluoro- methyl-pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3- difluoro-phenyl, 2,5-dimethyl-2H-pyrazol-3-yl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-4-nitro phenyl, 3-fluoro-4-nitro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro pyrid-3-yl, 3-fluoro-pyrid-4-yl, 2-fluoro-3-trifluoromethyl-phenyl, 2-fluoro-5-trifluoro- methyl-phenyl, 4-fluoro-3-trifluoromethyl-phenyl, furan-2-yl, 2-methoxy-phenyl, 4- methoxy-phenyl, 4-methoxy-thiophen-3-yl, 2-methyl-phenyl, 3 -methyl -phenyl, 4-methyl- phenyl, 5 -methyl- 1 -phenyl- lH-pyrazol-4-yl, 3-methyl-pyrid-2-yl, 4-methyl-l,2,3-thiadiazol-
5- yl, 4-methylthio-phenyl, 2-methylthio-pyrid-3-yl, 2-methylthio-4-trifluoromethyl -phenyl, l-methyl-3 -trifluoromethyl- lH-pyrazol-4-yl, 2-nitro-phenyl, 3-nitro-phenyl, 4-nitro-phenyl, phenyl, 5-phenyl-furan-2-yl, pyrid-3-yl, pyrid-4-yl, l,2,3-thiadiazol-4-yl, thiophen-2-yl, 2- trifluoromethyl-phenyl and 4-trifluoromethyl-phenyl. Even more preferably Q1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of even more preferred groups for Q1 are biphenyl-4-yl, 3-chloro-2-fluoro-phenyl, 5-chloro- 2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2-methyl-phenyl, 2-chloro-phenyl, 3- chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3-chloro-5- trifluoromethyl-pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro- phenyl, 2-fluoro-pyrid-3-yl, 3-fluoro-pyrid-4-yl, 2-fluoro-3-trifluoromethyl-phenyl, 2-fluoro- 5 -trifluoromethyl -phenyl, 4-fluoro-3-trifluoromethyl-phenyl, 2-methoxy-phenyl, 4-methoxy- phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3 -methyl -pyrid-2-yl, 4- methylthio-phenyl, 2-methylthio-pyrid-3-yl, 2-methylthio-4-trifluoromethyl -phenyl, phenyl, pyrid-3-yl, pyrid-4-yl, 2 -trifluoromethyl -phenyl and 4 -trifluoromethyl -phenyl.
Yet even more preferably Q1 is phenyl substituted by one substituent selected from cyano, fluoro or chloro. Examples of yet even more preferred groups for Q1 are 2-chloro- phenyl, 3-chloro-phenyl, 4-cyano-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl and 4-fluoro- phenyl.
Most preferably Q1 is 4-fluoro-phenyl.
In one preferred embodiment of the embodiment (D), Q1 is aryl or aryl substituted by one to five substituents R3, which may be the same or different.
Preferably Q1 is phenyl or phenyl substituted by one to four substituents
independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl. Examples of preferred groups for Q1 are biphenyl-4-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo-phenyl, 3-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3-chloro-2- methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 3-chloro-2,4,5- trifluoro-phenyl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3- difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-4-nitro-phenyl, 3-fluoro-4-nitro- phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3-trifluoromethyl- phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 4-fluoro-3-trifluoromethyl-phenyl, 2-methoxy- phenyl, 4-methoxy-phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 4- methylthio-phenyl, 2-methylthio-4-trifluoromethyl -phenyl, 2-nitro-phenyl, 3-nitro-phenyl, 4- nitro-phenyl, phenyl, 2-trifluoromethyl-phenyl and 4-trifluoromethyl-phenyl. More preferably Q1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of more preferred groups for Q1 are biphenyl-4-yl, 5-bromo-2-hydroxy-phenyl, 2-bromo- phenyl, 3-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-hydroxy-phenyl, 3- chloro-2-methyl-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro- phenyl, 2,3-difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-4-nitro-phenyl, 3-fluoro-4 nitro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3-trifluoromethyl- phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 4-fluoro-3-trifluoromethyl-phenyl, 2-methoxy- phenyl, 4-methoxy-phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 4- methylthio-phenyl, 2-methylthio-4-trifluoromethyl -phenyl, 2-nitro-phenyl, 3 -nitro-phenyl, 4 nitro-phenyl, phenyl, 2-trifluoromethyl-phenyl and 4-trifluoromethyl-phenyl.
Even more preferably Q1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of even more preferred groups for Q1 are biphenyl-4-yl, 3-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro- phenyl, 3 -chloro-2 -hydroxy-phenyl, 3-chloro-2-methyl-phenyl, 2-chloro-phenyl, 3-chloro- phenyl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro-phenyl, 3-fluoro-4-hydroxy-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-3- trifluoromethyl -phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 4-fluoro-3-trifluoromethyl- phenyl, 2-methoxy-phenyl, 4-methoxy-phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl phenyl, 4-methylthio-phenyl, 2-methylthio-4-trifluoromethyl-phenyl, phenyl, 2- trifluoromethyl-phenyl and 4-trifluoromethyl-phenyl.
In one preferred embodiment of the embodiment (D) Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R3, which may be the same or different.
In a further preferred embodiment of the embodiment (D) Q1 is heteroaryl or heteroaryl substituted by one to five substituents R3, which may be the same or different.
Preferably Q1 is pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl, or pyridyl, pyrimidyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl or imidazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of preferred groups for Q1 are 5-bromo-furan-2-yl, 5- bromo-pyrid-3-yl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro- thiophen-2-yl, 3-chloro-5-trifluoromethyl-pyrid-2-yl, 2,5-dimethyl-2H-pyrazol-3-yl, 2- fluoro-pyrid-3-yl, 3-fluoro-pyrid-4-yl, furan-2-yl, lH-imidazol-4-yl, 4-methoxy-thiophen-3- yl, 5-methyl-3-phenyl-isoxazol-4-yl, 5-methyl-l-phenyl-lH-pyrazol-4-yl, 4-methyl-2- phenyl-pyrimid-5-yl, 4-methyl-2-phenyl-thiazol-5-yl, 3-methyl-pyrid-2-yl, 4-methyl- 1,2,3- thiadiazol-5-yl, 2-methylthio-pyrid-3-yl, l-methyl-3-trifluoromethyl-lH-pyrazol-4-yl, 1- methyl-3-trifluoromethyl-lH-pyrrol-4-yl, 5-phenyl-furan-2-yl, 5-phenyl-oxazol-4-yl, pyrid- 3-yl, pyrid-4-yl, l,2,3-thiadiazol-4-yl, l,2,5-trimethyl-lH-pyrrol-3-yl and thiophen-2-yl.
More preferably Q1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of more preferred groups for Q1 are 5-bromo-furan-2-yl, 5-bromo-pyrid-3-yl, 2- chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3-chloro- 5-trifluoromethyl-pyrid-2-yl, 2,5-dimethyl-2H-pyrazol-3-yl, 2-fluoro-pyrid-3-yl, 3-fluoro- pyrid-4-yl, furan-2-yl, 4-methoxy-thiophen-3-yl, 5-methyl-l-phenyl-lH-pyrazol-4-yl, 3- methyl-pyrid-2-yl, 4-methyl- l,2,3-thiadiazol-5-yl, 2-methylthio-pyrid-3-yl, l-methyl-3- trifluoromethyl-lH-pyrazol-4-yl, 5-phenyl-furan-2-yl, pyrid-3-yl, pyrid-4-yl, 1,2,3- thiadiazol-4-yl and thiophen-2-yl.
Even more preferably Q1 is pyridyl or pyridyl substituted by one to three substituents independently selected from cyano, hydroxy, fluoro, chloro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of even more preferred groups for Q1 are 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 2-fluoro-pyrid-3-yl, 3-fluoro-pyrid-4-yl, 3-methyl- pyrid-2-yl, 2-methylthio-pyrid-3-yl, pyrid-3-yl and pyrid-4-yl.
Preferably Q2 is a moiety of formula (II).
Preferably Y1 is cyano, chloro, bromo, methyl, ethyl, trifluoromethyl or
methoxymethy 1.
More preferably Y1 is cyano, chloro, bromo, methyl or trifluoromethyl.
Even more preferably Y1 is methyl or ethyl.
Most preferably Y1 is methyl.
Preferably Y2 is hydrogen, fluoro, chloro or methyl. Most preferably Y2 is hydrogen.
Preferably Y3 is heptafiuoropropyl, heptafluoroprop-2-yl, heptafiuoropropylthio, heptafiuoropropylsulfinyl, heptafluoropropylsulfonyl, heptafiuoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, heptafiuoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
Most preferably Y3 is heptafluoroprop-2-yl.
Preferably Y4 is hydrogen, fiuoro, chloro or methyl.
Most preferably Y4 is hydrogen.
Preferably Y5 is cyano, chloro, bromo, methyl, ethyl or trifiuoromethyl.
More preferably Y5 is cyano, chloro, bromo, methyl or trifiuoromethyl.
Even more preferably Y5 is methyl or ethyl.
Most preferably Y5 is methyl.
Preferably Y6 is cyano, chloro, bromo, methyl, ethyl, trifiuoromethyl or methoxymethy 1.
More preferably Y6 is cyano, chloro, bromo, methyl or trifiuoromethyl.
Even more preferably Y6 is methyl or ethyl.
Most preferably Y6 is methyl.
Preferably Y7 is hydrogen, fiuoro, chloro or methyl.
Most preferably Y7 is hydrogen.
Preferably Y8 is heptafiuoropropyl, heptafluoroprop-2-yl, heptafiuoropropylthio, heptafiuoropropylsulfinyl, heptafluoropropylsulfonyl, heptafiuoroprop-2-ylthio, heptafluoroprop-2-ylsulfmyl, heptafiuoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
Most preferably Y8 is heptafluoroprop-2-yl.
Preferably Y9 is cyano, chloro, bromo, methyl, ethyl, trifiuoromethyl or methoxymethy 1.
More preferably Y9 is cyano, chloro, bromo, methyl or trifiuoromethyl.
Even more preferably Y9 is methyl or ethyl.
Most preferably Y9 is methyl.
One preferred embodiment of the embodiment (D) are compounds of formula (la) wherein A1, A2, A3, A4 are CH.
Another preferred embodiment of the embodiment (D) are compounds of formula (lb) wherein A1 is C-F, and A2, A3, and A4 are CH.
A further preferred embodiment of the embodiment (D) are compounds of formula (Ic) wherein A2 is C-F, and A1, A3, and A4 are CH. Yet another preferred embodiment of the embodiment (D) are compounds of formula (Id) wherein A3 is C-F, and A1, A2, and A4 are CH.
Yet a further preferred embodiment of the embodiment (D) are compounds of formula (Ie) wherein A4 is C-F, and A1, A2, and A3 are CH.
Another preferred embodiment of the embodiment (D) are compounds of formula (If) wherein A1 is C-CN, and A2, A3, and A4 are CH.
A further preferred embodiment of the embodiment (D) are compounds of formula (Ig) wherein A2 is C-CN, and A1, A3, and A4 are CH.
Yet another preferred embodiment of the embodiment (D) are compounds of formula (Ih) wherein A3 is C-CN, and A1, A2, and A4 are CH.
Yet a further preferred embodiment of the embodiment (D) are compounds of formula (Ij) wherein A4 is C-CN, and A1, A2, and A3 are CH.
One preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q2 is 2,6-dimethyl-4-perfluoroisopropyl-phenyl.
Another preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q2 is 2-ethyl-6-methyl-4-perfluoroisopropyl-phenyl.
A further preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q2 is 2,6-diethyl-4-perfluoroisopropyl-phenyl.
Yet another preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q2 is 2-methoxymethyl-6-methyl-4-perfluoroisopropyl-phenyl.
Yet another preferred embodiment of the embodiment (D) are compounds of formula (I) wherein Q2 is 2-methyl-4-perfluoroisopropyl-phenyl.
In one preferred embodiment of the embodiment (D), each X is independently hydrogen, halogen, Ci-C4alkyl or trifluoromethyl.
In one preferred embodiment of the embodiment (D), Q1 is aryl or aryl substituted by one to five substituents R3, which may be the same or different, or Q1 is heteroaryl or heteroaryl substituted by one to five substituents R3, which may be the same or different.
In one preferred embodiment of the embodiment (D), each R3 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2- C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, Ci-C3alkoxy, Ci- C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfmyl, Ci-C3haloalkyl- sulfmyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, Ci-C4alkylamino, di-(Ci-C4alkyl)- amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxycarbonyl, Ci-C4alkyl- carbonylamino or phenyl.
In one preferred embodiment of the embodiment (D), Y1 and Y5 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkylthio, Ci-Cshaloalkylthio, Ci-C3alkylsulfinyl, Ci-Cshaloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-Cshaloalkylsulfonyl.
In one preferred embodiment of the embodiment (D), Y6 and Y9 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl.
Certain intermediates are novel and as such form a further aspect of the invention. One group of novel intermediates are compounds of formula (VIII')
Figure imgf000080_0001
1 2 3 4 1 2 2 2
wherein A , A A\ A , R , R Gz and Qz are as defined in relation to formula (I); or salts or N-oxides thereof.
The compounds in Tables 1 to 15 below illustrate the compounds of the invention according to the embodiment (D).
Table 1 :
Table 1 provides 25 compounds of formula (la) wherein Q2 is 2,6-dimethyl-4- perfluoroisopropyl-phenyl and Q1 has the values listed in the table below.
Figure imgf000080_0002
Compound numbers Q
1.01 5-bromo-furan-2-yl
1.02 2-bromo-phenyl Compound numbers Q
1.03 5 -bromo -pyrid-3 -yl
1.04 2-chloro-5 -nitro-phenyl
1.05 2-chloro-phenyl
1.06 3-chloro-phenyl
1.07 2-chloro-pyrid-3 -yl
1.08 2-chloro-pyrid-4-yl
1.09 6-chloro-pyrid-3 -yl
1.10 5-chloro-thiophen-2-yl
1.11 3 -chloro-5 -trifluoromethyl-pyrid-2- yl
1.12 4-cyano-phenyl
1.13 2,5-dichloro-phenyl
1.14 2,3-difluoro-phenyl
1.15 1 ,3 -dimethyl-pyrazol-5 -yl
1.16 4-fluoro-phenyl
1.17 2-fluoro-pyrid-3 -yl
1.18 2-fluoro-3 -trifluoromethyl -phenyl
1.19 2-methyl -phenyl
1.20 3 -methyl -pyrid-2-yl
1.21 2-methylthio-pyrid-3-yl
1.22 4-nitro-phenyl
1.23 phenyl
1.24 1 ,2,3-thiadiazol-4-yl
1.25 thiophen-2-yl
Table 2:
Table 2 provides 25 compounds of formula (la) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 3:
Table 3 provides 25 compounds of formula (la) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1. Table 4:
Table 4 provides 25 compounds of formula (lb) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000082_0001
Table 5:
Table 5 provides 25 compounds of formula (lb) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 6:
Table 6 provides 25 compounds of formula (lb) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 7:
Table 7 provides 25 compounds of formula (Ic) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000082_0002
Table 8:
Table 8 provides 25 compounds of formula (Ic) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 9:
Table 9 provides 25 compounds of formula (Ic) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 10:
Table 10 provides 25 compounds of formula (Id) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000083_0001
Table 11 :
Table 11 provides 25 compounds of formula (Id) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 12:
Table 12 provides 25 compounds of formula (Id) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 13:
Table 13 provides 25 compounds of formula (Ie) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000083_0002
Table 14:
Table 14 provides 25 compounds of formula (Ie) wherein Q2 is 2 -methyl -4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 15:
Table 15 provides 25 compounds of formula (Ie) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 16:
Table 16 provides 25 compounds of formula (If) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000084_0001
Table 17:
Table 17 provides 25 compounds of formula (If) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 18:
Table 18 provides 25 compounds of formula (If) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 19:
Table 19 provides 25 compounds of formula (Ig) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000084_0002
Table 20:
Table 20 provides 25 compounds of formula (Ig) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 21 :
Table 21 provides 25 compounds of formula (Ig) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 22:
Table 22 provides 25 compounds of formula (Ih) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000085_0001
Table 23:
Table 23 provides 25 compounds of formula (Ih) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 24:
Table 24 provides 25 compounds of formula (Ih) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 25:
Table 25 provides 25 compounds of formula (Ij) wherein Q2 is 2,6-dimethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Figure imgf000085_0002
Table 26:
Table 26 provides 25 compounds of formula (Ij) wherein Q2 is 2-methyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
Table 27:
Table 27 provides 25 compounds of formula (Ij) wherein Q2 is 2,6-diethyl-4-perfluoro- isopropyl-phenyl and Q1 has the values listed in Table 1.
The following Examples illustrate, but do not limit, the invention according to the embodiment (D):
N-[3-(4-fluoro-benzoylamino)-phenyl]-2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l- trifluoromethyl-ethyl)-benzamide N-[3-(4-cyano-benzoylamino)-phenyl]-2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l-trifluorome ethyl)-benzamide
N-[4-cyano-3 -(4-fluoro-benzoylamino)-phenyl] -2,6-dimethyl-4-( 1 ,2,2,2-tetrafluoro- 1 - trifluoromethyl-ethyl)-benzamide
Or a compound as listed in the Table A
Table A: Compounds of formula (la):
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
Figure imgf000089_0001
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
phenyl-
Or a compound as listed in the Table B Table B: Compounds of formula (lb):
Figure imgf000095_0001
Figure imgf000096_0001
phenyl- fluoroisopropyl-phenyl-
Or a compound as listed in the Table C
pounds of formula (Ie):
(le)
Figure imgf000096_0002
Figure imgf000097_0001
fluoroisopropyl-phenyl-
Or a compound as listed in the Table D Table D: Compounds of formula (If):
Figure imgf000098_0001
Figure imgf000098_0003
In an embodiment (E), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000098_0002
A1, A2, A3 and A4 are independently of one another C-R3, C-R5 or nitrogen, provided that at least one of A1, A2, A3 and A4 is C-R3 and no more than two of A1, A2, A3 and A4 are nitrogen;
R1 and R2 are independently of each other hydrogen, Ci-C4alkyl, C2-C4alkenyl, C2- C4alkynyl, Ci-C4alkylcarbonyl, hydroxy, Ci-C4alkylcarbonyloxy, arylcarbonyloxy or arylcarbonyloxy wherein the aryl ring is substituted by one to five substituents independently selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy or Ci-C4haloalkoxy;
G1 and G2 are independently of each other oxygen or sulfur;
each R3 is independently cyano, thiocyanato, aminothiocarbonyl, N-Ci-C4alkyl-amino- thiocarbonyl or N,N-di-Ci-C4alkyl-aminothiocarbonyl;
each R5 is independently hydrogen, halogen, Ci-C4alkyl, Ci-C4haloalkyl or Ci-C4alkoxy; Q1 is aryl or aryl substituted by one to five substituents R6, which may be the same or different, or Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R6, which may be the same or different; wherein
each R6 is independently cyano, nitro, hydroxy, halogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci- C4alkoxy-Ci-C4-alkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3- C6cycloalkyl, C3-C6halocycloalkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, Ci-C4alkoxy-Ci-C4- alkoxy, Ci-C6alkylthio, Ci-C6haloalkylthio, Ci-C6alkylsulfinyl, Ci-C6haloalkylsulfmyl, Ci- Cealkylsulfonyl, Ci-Cehaloalkylsulfonyl, N-Ci-Cealkylamino, N,N-di-(Ci-C6alkyl)amino, N,N-di-(C i -C6alkyl)aminocarbonyl, N,N-di-(C i -C6alkyl)aminosulfonyl, C i -Cealkylcarbonyl, Ci-C6alkylcarbonyloxy, Ci-C6alkoxycarbonyl, Ci-Cealkylcarbonylamino, aryl or aryl which is substituted by one to five substituents independently selected from cyano, nitro, hydroxy, halogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy or Ci-C6haloalkoxy, or heteroaryl or heteroaryl which is substituted by one to five substituents independently selected from cyano, nitro, hydroxy, halogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy or Ci- C6haloalkoxy; and
Q2 is a moiety of formula (II) or (III)
Figure imgf000099_0001
wherein
Y1 and Y5 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci- C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Ci- C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y3 is C2-C6perfluoroalkyl, Ci-C6perfluoroalkylthio, Ci-C6perfluoroalkylsulfinyl or Ci-C6per- fluoroalkylsulfonyl;
Y2 and Y4 are independently of each other hydrogen, halogen or Ci-C4alkyl;
Y6 and Y9 are independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Q- C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Q- C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y8 is Ci-C4haloalkoxy, C2-C6perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-C6perfluoroalkyl- sulfinyl or Ci-C6perfluoroalkylsulfonyl; Y7 is hydrogen, halogen or Ci-C4alkyl;
or a salt or N-oxide thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (E) the preferred values of A1, A2, A3, A4, R1, R2, G1, G2, R3, R5, Q1, R6, Q2, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are, in any combination, as set out below.
Preferably A1 is C-R3 or C-R5.
Preferably A2 is C-R3 or C-R5.
Preferably A3 is C-R3 or C-R5.
Preferably A4 is C-R3 or C-R5.
Preferably one, two or three of A1, A2, A3 and A4 are C-R3.
More preferably one or two of A1, A2, A3 and A4 are C-R3.
Most preferably one of A1, A2, A3 and A4 is C-R3.
Preferably R1 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl, hydroxy, acetyloxy or benzoyloxy.
More preferably R1 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl or hydroxy. Even preferably R1 is hydrogen, methyl or ethyl.
Yet even more preferably R1 is hydrogen or methyl.
Most preferably R1 is hydrogen.
Preferably R2 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl, hydroxy, acetyloxy or benzoyloxy.
More preferably R2 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl or hydroxy.
Even preferably R2 is hydrogen, methyl or ethyl.
Yet even more preferably R2 is hydrogen or methyl.
Most preferably R2 is hydrogen.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably each R3 is independently cyano, thiocyanato or aminothiocarbonyl.
More preferably each R3 is independently cyano or thiocyanato.
Most preferably each R3 is cyano.
Preferably each R5 is independently hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl or methoxy. More preferably each R5 is independently hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl.
Even more preferably each R5 is independently hydrogen, fluoro, methyl or trifluoromethyl.
Yet even more preferably each R5 is independently hydrogen or fluoro.
Most preferably each R5 is hydrogen.
Preferably Q1 is aryl or aryl substituted by one to five substituents R6, which may be the same or different, or Q1 is heteroaryl or heteroaryl substituted by one to five substituents R6, which may be the same or different.
More preferably Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Examples of such more preferred groups for Q1 are 5-bromo-furan-2-yl, 2-bromo-phenyl, 5-bromo-pyrid-3-yl, 2-chloro-4-fluoro-phenyl, 3- chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 3-chloro-2-methyl-phenyl, 2-chloro-4- nitro-phenyl, 2-chloro-5-nitro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 2-chloro-pyrid-3-yl, 2-chloro-pyrid-4-yl, 6-chloro-pyrid-3-yl, 5-chloro-thiophen-2-yl, 3 -chloro-5 -trifluoromethyl - pyrid-2-yl, 4-cyano-2-fluoro-phenyl, 4-cyano-phenyl, 2,5-dichloro-phenyl, 2,3-difluoro- phenyl, l,3-dimethyl-lH-pyrazol-5-yl, 2-fluoro-phenyl, 4-fluoro-phenyl, 2-fluoro-pyrid-3-yl, 2-fluoro-3 -trif uoromethyl-phenyl, 2-fluoro-5 -trif uoromethyl-phenyl, 4-fluoro-3 -trifluoro- methyl-phenyl, furan-2-yl, 2-methoxy-phenyl, 2-methyl-phenyl, 3 -methyl -pyrid-2-yl, 4- methyl-l,2,3-thiadiazol-5-yl, 4-methylthio-phenyl, 2-methylthio-pyrid-3-yl, 4-nitro-phenyl, phenyl, pyrid-3-yl, pyrid-4-yl, l,2,3-thiadiazol-4-yl, thiophen-2-yl, 2-trifluoromethoxy- phenyl, 4-trifluoromethoxy-phenyl, 2 -trifluoromethyl-phenyl and 4-trif uoromethyl-phenyl.
Even more preferably Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
Yet even more preferably Q1 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl. Most preferably Q1 is phenyl substituted by one or two substituents selected from chloro, fluoro or methyl.
In one preferred embodiment of the embodiment (E) Q1 is 2-chloro-4-fluoro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 3-chloro-2-fluoro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 5-chloro-2-fluoro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 3-chloro-2-methyl-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 2-chloro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 3-chloro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 4-cyano-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 2,5-dichloro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 2,3-difluoro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 2-fluoro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 4-fluoro-phenyl.
In one preferred embodiment of the embodiment (E) Q1 is 2-methyl-phenyl.
A particularly preferred group of compounds are compounds of formula (I) wherein Q1 is aryl or aryl substituted by one to five substituents R6, which may be the same or different.
Preferably Q1 is phenyl or phenyl substituted by one to four substituents
independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
More preferably Q1 is phenyl or phenyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
Even more preferably Q1 is phenyl or phenyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl.
Another particularly preferred group of compounds are compounds of formula (I) wherein Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R6, which may be the same or different. The heterocyclyl group is preferably a heteroaryl group.
Preferably Q1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfinyl, methyl- sulfonyl or phenyl.
More preferably Q1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1 ,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
Even more preferably Q1 is pyridyl or pyridyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
Most preferably Q1 is pyridyl substituted by one to two substituents independently selected from chloro, fluoro or methyl.
Preferably each R6 is independently cyano, nitro, hydroxy, halogen, Ci-C6alkyl, Ci- C6haloalkyl, Ci-C4alkoxy-Ci-C4-alkyl, C3-C6cycloalkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, Ci- C4alkoxy-Ci-C4-alkoxy, Ci-C6alkylthio, Ci-C6alkylsulfonyl, N,N-di-(Ci-C6alkyl)amino, N,N- di-(Ci-C6alkyl)aminocarbonyl, N,N-di-(Ci-C6alkyl)aminosulfonyl, Ci-C6alkylcarbonyl, Ci- Cealkylcarbonyloxy, Ci-C6alkoxycarbonyl or Ci-Cealkylcarbonylamino.
More preferably each R6 is independently cyano, nitro, hydroxy, bromo, chloro, fluoro, iodo, methyl, ethyl, n-propyl, prop-2-yl, n-butyl, tert-butyl, chloromethyl,
trifluoromethyl, methoxymethyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, 2,2,2- trifluoroethoxy, 2-methoxy-ethoxy, methylthio, ethylthio, n-propylthio, n-butylthio, methylsulfonyl, prop-2-ylsulfonyl, N,N-dimethylamino, N,N-dimethylaminocarbonyl, N,N- dimethylaminosulfonyl, methylcarbonyl, methylcarbonyloxy, methoxycarbonyl, ethoxy- carbonyl, methylcarbonylamino, aryl or aryl which is substituted by one to five substituents independently selected from cyano, nitro, hydroxy, chloro, fluoro, methyl, ethyl,
trifluoromethyl, methoxy or trifluoromethoxy, or heteroaryl or heteroaryl which is substituted by one to five substituents independently selected from cyano, nitro, hydroxy, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy or trifluoromethoxy.
Most preferably each R6 is independently cyano, nitro, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, N,N-dimethylamino or methoxycarbonyl.
Preferably Q2 is a moiety of formula (II).
Preferably Y1 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl. More preferably Y1 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
Even more preferably Y1 is bromo, chloro, methyl, ethyl or methoxymethyl.
Yet even more preferably Y1 is bromo, methyl or ethyl.
Even more preferably Y1 is methyl or ethyl.
Most preferably Y1 is methyl.
Preferably Y2 is hydrogen, chloro, fluoro or methyl.
Most preferably Y2 is hydrogen.
Preferably Y3 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
In one embodiment of the embodiment (E) Y3 is C2-C6perfluoroalkyl, more preferably Y3 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
In one embodiment of the embodiment (E) Y3 is heptafluoroprop-2-yl.
In one embodiment of the embodiment (E) Y3 is nonafluorobut-2-yl.
Preferably Y4 is hydrogen, chloro, fluoro or methyl.
Most preferably Y4 is hydrogen.
Preferably Y5 is cyano, halogen, methyl, ethyl or trifluoromethyl.
More preferably Y5 is cyano, bromo, chloro, methyl, ethyl or trifluoromethyl.
Even more preferably Y5 is bromo, chloro, methyl or ethyl.
Yet even more preferably Y5 is bromo, methyl or ethyl.
Even more preferably Y5 is methyl or ethyl.
Most preferably Y5 is methyl.
Preferably Y6 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl. More preferably Y6 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
Even more preferably Y6 is bromo, chloro, methyl, ethyl or methoxymethyl.
Yet even more preferably Y6 is bromo, methyl or ethyl.
Even more preferably Y6 is methyl or ethyl.
Most preferably Y6 is methyl.
Preferably Y7 is hydrogen, chloro, fluoro or methyl.
Most preferably Y7 is hydrogen. Preferably Y is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfmyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
In one embodiment of the embodiment (E) Y8 is C2-C6perfluoroalkyl, more preferably Y8 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
In one embodiment of the embodiment (E) Y8 is heptafluoroprop-2-yl.
In one embodiment of the embodiment (E) Y8 is nonafluorobut-2-yl.
Preferably Y9 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl.
More preferably Y9 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
Even more preferably Y9 is bromo, chloro, methyl, ethyl or methoxymethyl.
Yet even more preferably Y9 is bromo, methyl or ethyl.
Even more preferably Y9 is methyl or ethyl.
Most preferably Y9 is methyl.
A preferred embodiment of the embodiment (E) are compounds of formula (la) wherein A1 is C-CN, and A2, A3, A4 are CH.
A preferred embodiment of the embodiment (E) are compounds of formula (lb) wherein A2 is C-CN, and A1, A3, and A4 are CH.
A preferred embodiment of the embodiment (E) are compounds of formula (Ic) wherein A3 is C-CN, and A1, A2, and A4 are CH.
A preferred embodiment of the embodiment (E) are compounds of formula (Id) wherein A4 is C-CN, and A1, A2, and A3 are CH.
A preferred embodiment of the embodiment (E) are compounds of formula (Ie) wherein A1 is C-CN, A4 is C-F, and A2 and A3 are CH.
A preferred embodiment of the embodiment (E) are compounds of formula (If) wherein A1 is C-CN, A2 and A4 are C-F, and A3 is CH.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-dimethyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2-ethyl-6-methyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-diethyl-4- (heptafluoroprop-2-yl)-phenyl. In a preferred embodiment of the embodiment (E) Q2 is 2-methoxymethyl-6-methyl- 4-(heptafluoroprop -2 -yl)-pheny 1.
In a preferred embodiment of the embodiment (E) Q2 is 2-bromo-6-methyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2-bromo-6-ethyl-4-
(heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-dichloro-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-dibromo-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-dimethyl-4- (nonafluorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2-ethyl-6-methyl-4- (nonafluorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-diethyl-4-(nonafluorobut-
2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2-methoxymethyl-6-methyl- 4-(nonafluorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2-bromo-6-methyl-4- (nonafluorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2-bromo-6-ethyl-4- (nonafluorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-dichloro-4- (nonafluorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (E) Q2 is 2,6-dibromo-4-
(nonafluorobut-2-yl)-phenyl.
In one embodiment of the embodiment (E) of the invention R1 and R2 are
independently of each other hydrogen, Ci-C4alkyl, or Ci-C4alkylcarbonyl. The preferences for R1 and R2 are the same as set out for compounds of formula (I) except that R1 and R2 cannot be allyl, propargyl, hydroxy, acetyloxy or benzoyloxy.
In one embodiment of the embodiment (E) of the invention each R3 is independently cyano, thiocyanato or N-Ci-C4alkyl-aminothiocarbonyl. The preferences for R3 are the same as set out for compounds of formula (I) except that R3 cannot be aminothiocarbonyl. In one embodiment of the embodiment (E) of the invention each R5 is independently hydrogen, halogen, Ci-C4alkyl or trifluoromethyl. The preferences for R5 are the same as set out for compounds of formula (I) except that R5 cannot be methoxy.
In one embodiment of the embodiment (E) of the invention each R6 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, Ci-C3alkoxy, Ci- C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfmyl, Ci-C3haloalkyl- sulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, N-Ci-C4alkylamino, N,N-di-(Ci- C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxycarbonyl, Ci- C4alkylcarbonylamino or phenyl. The preferences for R6 are the same as set out for compounds of formula (I).
In one embodiment of the embodiment (E) of the invention Y1 and Y5 are
independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkylthio, Ci- C3haloalkylthio, Ci-C3alkylsulfmyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or d- C3haloalkylsulfonyl. The preferences for Y1 and Y5 are the same as set out for compounds of formula (I) except that Y1 cannot be methoxymethyl.
In one embodiment of the embodiment (E) of the invention Y6 and Y9 are
independently of each other cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkylthio, Ci- C3haloalkylthio, Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci- C3haloalkylsulfonyl. The preferences for Y6 and Y9 are the same as set out for compounds of formula (I) except that Y6 and Y9 cannot be methoxymethyl.
The compounds in Tables 1 to 67 below illustrate the compounds of the invention according to the embodiment (E).
Table 1 :
Table 1 provides 38 compounds of formula (la) wherein Q is 2,6-dimethyl-4- prop-2-yl -phenyl and Q1 has the values listed in the table below.
Figure imgf000108_0001
Compound numbers Q
1.01 5-bromo-furan-2-yl
1.02 2-bromo-phenyl
1.03 5 -bromo -pyrid-3 -yl
1.04 2-chloro-4-fluoro-phenyl
1.05 5 -chloro-2-fluoro-phenyl
1.06 2-chloro-4-nitro-phenyl
1.07 2-chloro-5 -nitro-phenyl
1.08 2-chloro-phenyl
1.09 3-chloro-phenyl
1.10 2-chloro-pyrid-3-yl
1.11 2-chloro-pyrid-4-yl
1.12 6-chloro-pyrid-3-yl
1.13 5-chloro-thiophen-2-yl
1.14 3 -chloro-5 -trifluoromethyl-pyrid-2- yl
1.15 4-cyano-phenyl
1.16 2,5-dichloro-phenyl
1.17 2,3-difluoro-phenyl
1.18 1 ,3-dimethyl-lH-pyrazol-5-yl
1.19 2-fluoro-phenyl
1.20 4-fluoro-phenyl
1.21 2-fluoro-pyrid-3 -yl Compound numbers Q
1.22 2-fluoro-3 -trifluoromethyl -phenyl
1.23 2-fluoro-5 -trifluoromethyl -phenyl
1.24 4-fluoro-3 -trifluoromethyl -phenyl
1.25 furan-2-yl
1.26 2-methoxy-phenyl
1.27 2-methyl -phenyl
1.28 3 -methyl -pyrid-2-yl
1.29 4-methyl-l ,2,3-thiadiazol-5-yl
1.30 2-methylthio-pyrid-3-yl
1.31 4-nitro-phenyl
1.32 phenyl
1.33 1 ,2,3-thiadiazol-4-yl
1.34 thiophen-2-yl
1.35 2-trifluoromethoxy-phenyl
1.36 4-trifluoromethoxy-phenyl
1.37 2-trifluoromethyl-phenyl
1.38 4-trifluoromethyl-phenyl
Table 2:
Table 2 provides 38 compounds of formula (la) wherein Q2 is 2-ethyl-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 3:
Table 3 provides 38 compounds of formula (la) wherein Q2 is 2,6-diethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 4:
Table 4 provides 38 compounds of formula (la) wherein Q2 is 2-methoxymethyl-6-methyl-4- (heptafluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 5:
Table 5 provides 38 compounds of formula (la) wherein Q2 is 2-bromo-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1. Table 6:
Table 6 provides 38 compounds of formula (la) wherein Q2 is 2-bromo-6-ethyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 7:
Table 7 provides 38 compounds of formula (la) wherein Q2 is 2,6-dichloro-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 8:
Table 8 provides 38 compounds of formula (la) wherein Q2 is 2,6-dibromo-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 9:
Table 9 provides 38 compounds of formula (la) wherein Q2 is 2,6-dimethyl-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 10:
Table 10 provides 38 compounds of formula (la) wherein Q2 is 2-ethyl-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 11 :
Table 11 provides 38 compounds of formula (la) wherein Q2 is 2,6-diethyl-4-(nonafluorobut- 2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 12:
Table 12 provides 38 compounds of formula (la) wherein Q2 is 2-methoxymethyl-6-methyl- 4-(nonafluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 13:
Table 13 provides 38 compounds of formula (la) wherein Q2 is 2-bromo-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 14:
Table 14 provides 38 compounds of formula (la) wherein Q2 is 2-bromo-6-ethyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 15:
Table 15 provides 38 compounds of formula (la) wherein Q2 is 2,6-dichloro-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 16:
Table 16 provides 38 compounds of formula (la) wherein Q2 is 2,6-dibromo-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1. Table 17:
Table 17 provides 38 compounds of formula (la') wherein Q2 is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in the table below.
Figure imgf000111_0001
Table 18:
Table 18 provides 38 compounds of formula (la') wherein Q2 is 2-ethyl-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 19:
Table 19 provides 38 compounds of formula (la') wherein Q2 is 2,6-diethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 20:
Table 20 provides 38 compounds of formula (la') wherein Q2 is 2-methoxymethyl-6-methyl- 4-(heptafluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 21 :
Table 21 provides 38 compounds of formula (la') wherein Q2 is 2-bromo-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 22:
Table 22 provides 38 compounds of formula (la') wherein Q2 is 2-bromo-6-ethyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 23:
Table 23 provides 38 compounds of formula (la') wherein Q2 is 2,6-dichloro-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 24:
Table 24 provides 38 compounds of formula (la') wherein Q2 is 2,6-dibromo-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 25:
Table 25 provides 38 compounds of formula (la') wherein Q2 is 2,6-dimethyl-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1. Table 26:
Table 26 provides 38 compounds of formula (la') wherein Q2 is 2-ethyl-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 27:
Table 27 provides 38 compounds of formula (la') wherein Q2 is 2,6-diethyl-4- (nonafluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 28:
Table 28 provides 38 compounds of formula (la') wherein Q2 is 2-methoxymethyl-6-methyl- 4-(nonafluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 29:
Table 29 provides 38 compounds of formula (la') wherein Q2 is 2-bromo-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 30:
Table 30 provides 38 compounds of formula (la') wherein Q2 is 2-bromo-6-ethyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 31 :
Table 31 provides 38 compounds of formula (la') wherein Q2 is 2,6-dichloro-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 32:
Table 32 provides 38 compounds of formula (la') wherein Q2 is 2,6-dibromo-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 33:
Table 33 provides 38 compounds of formula (lb) wherein Q2 is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Figure imgf000112_0001
Table 34:
Table 34 provides 38 compounds of formula (Ic) wherein Q2 is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Figure imgf000113_0001
Table 35:
Table 35 provides 38 compounds of formula (Id) wherein Q2 is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Figure imgf000113_0002
Table 36:
Table 36 provides 38 compounds of formula (le) wherein Q2 is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in the table below.
Figure imgf000113_0003
Table 37:
Table 37 provides 38 compounds of formula (le) wherein Q2 is 2-ethyl-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 38:
Table 38 provides 38 compounds of formula (le) wherein Q2 is 2,6-diethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 39:
Table 39 provides 38 compounds of formula (le) wherein Q2 is 2-methoxymethyl-6-methyl- 4-(heptafluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1. Table 40:
Table 40 provides 38 compounds of formula (le) wherein Q2 is 2-bromo-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 41 :
Table 41 provides 38 compounds of formula (le) wherein Q2 is 2-bromo-6-ethyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 42:
Table 42 provides 38 compounds of formula (le) wherein Q2 is 2,6-dichloro-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 43:
Table 43 provides 38 compounds of formula (le) wherein Q2 is 2,6-dibromo-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 44:
Table 44 provides 38 compounds of formula (le) wherein Q2 is 2,6-dimethyl-4-(nonafiuoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 45:
Table 45 provides 38 compounds of formula (le) wherein Q2 is 2-ethyl-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 46:
Table 46 provides 38 compounds of formula (le) wherein Q2 is 2,6-diethyl-4-(nonafiuorobut- 2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 47:
Table 47 provides 38 compounds of formula (le) wherein Q2 is 2-methoxymethyl-6-methyl- 4-(nonafluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 48:
Table 48 provides 38 compounds of formula (le) wherein Q2 is 2-bromo-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 49:
Table 49 provides 38 compounds of formula (le) wherein Q2 is 2-bromo-6-ethyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 50:
Table 50 provides 38 compounds of formula (le) wherein Q2 is 2,6-dichloro-4-(nonafiuoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1. Table 51 :
Table 51 provides 38 compounds of formula (Ie) wherein Q2 is 2,6-dibromo-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 52:
Table 52 provides 38 compounds of formula (If) wherein Q2 is 2,6-dimethyl-4-(heptafluoro prop-2-yl)-phenyl and Q1 has the values listed in the table below.
Figure imgf000115_0001
Table 53:
Table 53 provides 38 compounds of formula (If) wherein Q2 is 2-ethyl-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 54:
Table 54 provides 38 compounds of formula (If) wherein Q2 is 2,6-diethyl-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 55:
Table 55 provides 38 compounds of formula (If) wherein Q2 is 2-methoxymethyl-6-methyl- 4-(heptafluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 56:
Table 56 provides 38 compounds of formula (If) wherein Q2 is 2-bromo-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 57:
Table 57 provides 38 compounds of formula (If) wherein Q2 is 2-bromo-6-ethyl-4-(hepta- fluoroprop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 58:
Table 58 provides 38 compounds of formula (If) wherein Q2 is 2,6-dichloro-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 59:
Table 59 provides 38 compounds of formula (If) wherein Q2 is 2,6-dibromo-4-(heptafluoro- prop-2-yl)-phenyl and Q1 has the values listed in Table 1. Table 60:
Table 60 provides 38 compounds of formula (If) wherein Q2 is 2,6-dimethyl-4-(nonafiuoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 61 :
Table 61 provides 38 compounds of formula (If) wherein Q2 is 2-ethyl-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 62:
Table 62 provides 38 compounds of formula (If) wherein Q2 is 2,6-diethyl-4-(nonafluorobut- 2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 63 :
Table 63 provides 38 compounds of formula (If) wherein Q2 is 2-methoxymethyl-6-methyl- 4-(nonafluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 64:
Table 64 provides 38 compounds of formula (If) wherein Q2 is 2-bromo-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 65 :
Table 65 provides 38 compounds of formula (If) wherein Q2 is 2-bromo-6-ethyl-4-(nona- fluorobut-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 66:
Table 66 provides 38 compounds of formula (If) wherein Q2 is 2,6-dichloro-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
Table 67:
Table 67 provides 38 compounds of formula (If) wherein Q2 is 2,6-dibromo-4-(nonafluoro- but-2-yl)-phenyl and Q1 has the values listed in Table 1.
The following Examples illustrate, but do not limit, the invention according to the embodiment (E):
4-cyano-3-(4'-cyano-benzoylamino)-N-[2,6-dimethyl-4-(l ,2,2,2-tetrafluoro-l- trifluoromethyl-ethyl)-phenyl]-benzamide (Compound No. Al of Table A)
4-cyano-3-[(4'-cyano-benzoyl)-ethyl-amino]-N-[2,6-dimethyl-4-(l ,2,2,2-tetrafluoro-l- trifluoromethyl-ethyl)-phenyl]-benzamide (Compound No. C43 of Table C)
Or a compound according to Table A or Table B or Table C or Table D or Table E or Table F or Table G. able A: Compounds of formula (la):
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000126_0001
Figure imgf000127_0001
Figure imgf000128_0001
Figure imgf000129_0001
Figure imgf000130_0001
Figure imgf000131_0001
Figure imgf000132_0001
Figure imgf000133_0001
Figure imgf000134_0001
Figure imgf000135_0001
Figure imgf000136_0001
Figure imgf000137_0001
Figure imgf000138_0001
Figure imgf000139_0001
Table B: Compounds of formula (lb):
Figure imgf000140_0001
Figure imgf000141_0001
Table C: Compounds of formula (la'):
Figure imgf000142_0001
Figure imgf000143_0001
Figure imgf000144_0001
Figure imgf000145_0001
Figure imgf000146_0001
yl)-phenyl-
Table D: Compounds of formula (Ie):
Figure imgf000146_0002
Figure imgf000147_0001
Figure imgf000148_0001
Figure imgf000149_0001
Figure imgf000150_0001
Figure imgf000151_0001
Figure imgf000152_0001
phenyl- prop-2-yl)-phenyl-
Table E: Compounds of formula (If):
Figure imgf000152_0002
Figure imgf000153_0001
Figure imgf000154_0001
Figure imgf000155_0001
Figure imgf000156_0001
Figure imgf000157_0001
Figure imgf000158_0001
Table F: Compounds of formula (Ic):
Figure imgf000159_0001
Figure imgf000159_0003
Table G: Compounds of formula (Id):
Figure imgf000159_0002
Figure imgf000160_0001
In an embodiment (F), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
G1
R2- N ^ G-R1 (I)
Q
wherein
A1, A2, A3 and A4 are independently of each other C-R4, C-R5 or nitrogen, provided that at least one of A1, A2, A3 and A4 is C-R4 and no more than two of A1, A2, A3 and A4 are nitrogen;
R1 is Ci-C6alkyl, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6halo- alkynyl, C3-C8cycloalkyl, C3-Cshalocycloalkyl, or
-E'-Z'-R6 wherein
E1 its Ci-C4alkylene, C2-C4alkenylene, C3-C4alkynylene, Ci-C4haloalkylene, C2-C4halo- alkenylene, or C3-C4haloalkynylene,
Z1 is - 0-, -S-, -SO-, or -S02-, and
R6 is hydrogen, Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Ci-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, or
-E2-R7 wherein E2 is Ci-C4alkylene, C2-C4alkenylene, C3-C4alkynylene, Ci-C4haloalkylene, C2-C4halo- alkenylene, or C3-C4haloalkynylene, and
R7 is C3-C8cycloalkyl, C3-C8halocycloalkyl, cyano, nitro, hydroxyl, or phenyl or phenyl substituted by one to five substituents R8, which may be the same or different, or pyridyl or pyridyl substituted with one to four substituents R9, which may be the same or different, or thiophenyl, or tetrahydrofuranyl;
R2 and R3 are independently of each other hydrogen, Ci-C4alkyl, C2-C4alkenyl, C2- C4alkynyl, Ci-C4alkylcarbonyl, Ci-C4haloalkylcarbonyl, hydroxy, Ci-C4alkylcarbonyloxy, arylcarbonyloxy or arylcarbonyloxy wherein the aryl ring is substituted by one to five substituents independently selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy or Ci-C4haloalkoxy;
G2 and G3 are independently of each other oxygen or sulfur;
each R4 is independently cyano, thiocyanato, aminothiocarbonyl, N-Ci-C4alkyl-amino- thiocarbonyl or N,N-di-Ci-C4alkyl-aminothiocarbonyl;
each R5 is independently hydrogen, halogen, Ci-C4alkyl, Ci-C4haloalkyl or Ci-C4alkoxy; each R8 is independently halogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, Ci-C6halo- alkoxy, Ci-C6alkylthio, Ci-C6haloalkylthio, Ci-C6alkylsulfinyl, Ci-C6haloalkylsulfinyl, Ci- Cealkylsulfonyl, Ci-Cehaloalkylsulfonyl, cyano, nitro, hydroxyl, Ci-C4alkylcarbonyl, Ci- C4haloalkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxycarbonyl, or pentafluorosulfanyl; each R9 is independently halogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, Ci-C6halo- alkoxy, Ci-C6alkylthio, Ci-C6haloalkylthio, Ci-C6alkylsulfinyl, Ci-C6haloalkylsulfinyl, Ci- Cealkylsulfonyl, Ci-Cehaloalkylsulfonyl, cyano, nitro, hydroxyl, Ci-C4alkylcarbonyl, Ci- C4haloalkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxycarbonyl, or pentafluorosulfanyl; and
Q is a moiety of formula (II) or (III)
Figure imgf000161_0001
wherein
Y1, Y2, Y4 and Y5 are independently of each other hydrogen, halogen, Ci-C6alkyl, Ci-C6- haloalkyl, Ci-C4alkoxy-Ci-C4-alkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, Ci-C6alkylthio, Ci- Cehaloalkylthio, Ci-Cealkylsulfinyl, Ci-Cehaloalkylsulfinyl, Ci-Cealkylsulfonyl, Ci- Cehaloalkylsulfonyl, pentafluorosulfanyl, cyano, or nitro, provided that no more than one of Y1 and Y5 is hydrogen, and
Y3 is Ci-C6haloalkyl, Ci-C6haloalkoxy, Ci-C6hydroxyhaloalkyl, Ci-Cehaloalkylthio, Ci- Cehaloalkylsulfinyl, Ci-Cehaloalkylsulfonyl, or pentafluorosulfanyl, or
Y6, Y7 and Y9 are independently of each other hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci- C4alkoxy-Ci-C4-alkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, Ci-C6alkylthio, Ci-C6haloalkylthio, Ci-Cealkylsulfinyl, Ci-Cehaloalkylsulfinyl, Ci-Cealkylsulfonyl, Ci-Cehaloalkylsulfonyl, pentafluorosulfanyl, cyano, or nitro, provided that no more than one of Y6 and Y9 is hydrogen, and
Y8 is Ci-C6haloalkyl, Ci-C6haloalkoxy, Ci-C6hydroxyhaloalkyl, Ci-C6haloalkylthio, Ci- Cehaloalkylsulfinyl, Ci-Cehaloalkylsulfonyl, or pentafluorosulfanyl;
or a salt or N-oxide thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (F) the preferred values of A1, A2, A3, A4, R1, R2, R3, G1, G2, G3, R4, R5, Q, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are, in any combination, as set out below.
Preferably A1 is C-R4 or C-R5.
Preferably A2 is C-R4 or C-R5.
Preferably A3 is C-R4 or C-R5.
Preferably A4 is C-R4 or C-R5.
Preferably one, two or three of A1, A2, A3 and A4 are C-R4 , more preferably one or two of A1, A2, A3 and A4 are C-R4, most preferably one of A1, A2, A3 and A4 is C-R4.
Preferably R1 is Ci-Cealkyl, Ci-Cehaloalkyl, C2-Cealkenyl, C2-Cehaloalkenyl, C2-
Cealkynyl, C2-Cehaloalkynyl, Cs-Cscycloalkyl, Cs-Cshalocycloalkyl, or cyano-Ci- C4alkylene, more preferably Ci-Cealkyl, Ci-Cehaloalkyl, C2-Cealkenyl or cyano-Ci- C4alkylene, most preferably methyl, ethyl, 2-fluoro-ethyl, 2-chloro-ethyl, 2-bromo-ethyl, 2- iodo-ethyl, 2-cyano-ethyl, 2,2-difluoro-ethyl, 2,2-dichloro-ethyl, 2,2,2-trifluoro-ethyl, 2,2,2- trichloro-ethyl, 2,2,2-tribromo-ethyl, propyl, 3-fluoro-propyl, 3-chloro-propyl, 3-bromo- propyl, l ,2-difluoro-prop-2-yl, l ,3-difluoro-prop-2-yl, l ,3-dichloro-prop-2-yl, l-chloro-3- fluoro-prop-2-yl, 3,3,3-trifluoro-propyl, butyl, 4,4,4-trifluoro-butyl or vinyl. Preferably R2 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl, 3,3,3-trichloro- propionyl, hydroxy, acetyloxy or benzoyloxy.
More preferably R2 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl or hydroxy. Even preferably R2 is hydrogen, methyl or ethyl.
Yet even more preferably R2 is hydrogen or methyl.
Most preferably R2 is hydrogen.
Preferably R3 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl, hydroxy, acetyloxy or benzoyloxy.
More preferably R3 is hydrogen, methyl, ethyl, allyl, propargyl, acetyl or hydroxy.
Even preferably R3 is hydrogen, methyl or ethyl.
Yet even more preferably R3 is hydrogen or methyl.
Most preferably R3 is hydrogen.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably G3 is oxygen.
Preferably each R4 is independently cyano, thiocyanato or aminothiocarbonyl, more preferably cyano or thiocyanato, most preferably cyano.
Preferably each R5 is independently hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl or methoxy.
More preferably each R5 is independently hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl.
Even more preferably each R5 is independently hydrogen, fluoro, methyl or trifluoromethyl.
Yet even more preferably each R5 is independently hydrogen or fluoro.
Most preferably each R5 is hydrogen.
Preferably Q is a moiety of formula (II).
Preferably Y1 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl. More preferably Y1 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
Even more preferably Y1 is bromo, chloro, methyl, ethyl or methoxymethyl.
Yet even more preferably Y1 is bromo, methyl or ethyl.
Even more preferably Y1 is methyl or ethyl.
Most preferably Y1 is methyl. Preferably Y2 is hydrogen, chloro, fluoro or methyl.
Most preferably Y2 is hydrogen.
Preferably Y3 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
In one embodiment of the embodiment (F) Y3 is C2-C6perfluoroalkyl, more preferably Y3 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
In one embodiment of the embodiment (F) Y3 is heptafluoroprop-2-yl.
In one embodiment of the embodiment (F) Y3 is nonafluorobut-2-yl.
Preferably Y4 is hydrogen, chloro, fluoro or methyl.
Most preferably Y4 is hydrogen.
Preferably Y5 is cyano, halogen, methyl, ethyl or trifluoromethyl.
More preferably Y5 is cyano, bromo, chloro, methyl, ethyl or trifluoromethyl.
Even more preferably Y5 is bromo, chloro, methyl or ethyl.
Yet even more preferably Y5 is bromo, methyl or ethyl.
Even more preferably Y5 is methyl or ethyl.
Most preferably Y5 is methyl.
Preferably Y6 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl. More preferably Y6 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
Even more preferably Y6 is bromo, chloro, methyl, ethyl or methoxymethyl.
Yet even more preferably Y6 is bromo, methyl or ethyl.
Even more preferably Y6 is methyl or ethyl.
Most preferably Y6 is methyl.
Preferably Y7 is hydrogen, chloro, fluoro or methyl.
Most preferably Y7 is hydrogen.
Preferably Y8 is heptafluoropropyl, heptafluoroprop-2-yl, heptafluoropropylthio, heptafluoropropylsulfinyl, heptafluoropropylsulfonyl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, heptafluoroprop-2-ylsulfonyl or nonafluorobut-2-yl.
In one embodiment of the embodiment (F) Y8 is C2-C6perfluoroalkyl, more preferably Y8 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
In one embodiment of the embodiment (F) Y8 is heptafluoroprop-2-yl.
In one embodiment of the embodiment (F) Y8 is nonafluorobut-2-yl. Preferably Y9 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl. More preferably Y9 is cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl .
Even more preferably Y9 is bromo, chloro, methyl, ethyl or methoxymethyl.
Yet even more preferably Y9 is bromo, methyl or ethyl.
Even more preferably Y9 is methyl or ethyl.
Most preferably Y9 is methyl.
A preferred embodiment of the embodiment (F) are compounds of formula (la) wherein A1 is C-CN, and A2, A3, A4 are CH.
A preferred embodiment of the embodiment (F) are compounds of formula (lb) wherein A2 is C-CN, and A1, A3, and A4 are CH.
A preferred embodiment of the embodiment (F) are compounds of formula (Ic) wherein A3 is C-CN, and A1, A2, and A4 are CH.
A preferred embodiment of the embodiment (F) are compounds of formula (Id) wherein A4 is C-CN, and A1, A2, and A3 are CH.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-dimethyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2-ethyl-6-methyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-diethyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2-methoxymethyl-6-methyl- 4-(heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2-bromo-6-methyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2-bromo-6-ethyl-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-dichloro-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-dibromo-4- (heptafluoroprop-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-dimethyl-4- (nonafluorobut-2-yl)-phenyl. In a preferred embodiment of the embodiment (F) Q2 is 2-ethyl-6-methyl-4- (nonafiuorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-diethyl-4-(nonafluorobut- 2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2-methoxymethyl-6-methyl-
4-(nonafiuorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2-bromo-6-methyl-4- (nonafiuorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2-bromo-6-ethyl-4- (nonafiuorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-dichloro-4- (nonafiuorobut-2-yl)-phenyl.
In a preferred embodiment of the embodiment (F) Q2 is 2,6-dibromo-4- (nonafiuorobut-2-yl)-phenyl.
In one embodiment of the embodiment (F) of the invention R2 and R3 are
independently of each other hydrogen, Ci-C4alkyl, or Ci-C4alkylcarbonyl. The preferences for R2 and R3 are the same as set out for compounds of formula (I) except that R2 and R3 cannot be allyl, propargyl, hydroxy, acetyloxy or benzoyloxy.
In one embodiment of the embodiment (F) of the invention each R5 is independently hydrogen, halogen, Ci-C4alkyl or trifluoromethyl. The preferences for R5 are the same as set out for compounds of formula (I) except that R5 cannot be methoxy.
In one embodiment of the embodiment (F) of the invention Y1, Y2, Y4 and Y5 are independently of each other hydrogen, halogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, Ci-C6alkylthio, Ci-C6haloalkylthio, Ci-C6alkylsulfmyl, d- C6haloalkylsulfinyl, Ci-C6alkylsulfonyl, Ci-C6haloalkylsulfonyl, pentafluorosulfanyl, cyano, or nitro, provided that no more than one of Y1 and Y5 is hydrogen. The preferences for Y1, Y2, Y4 and Y5 are the same as set out for compounds of formula (I) except that Y1 cannot be methoxymethy 1.
In one embodiment of the embodiment (F) of the invention Y6, Y7 and Y9 are independently of each other hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, Ci-C6alkoxy, Ci- C6haloalkoxy, Ci-C6alkylthio, Ci-Cehaloalkylthio, Ci-C6alkylsulfmyl, Ci- Cehaloalkylsulfinyl, Ci-Cealkylsulfonyl, Ci-Cehaloalkylsulfonyl, pentafluorosulfanyl, cyano, or nitro, provided that no more than one of Y6 and Y9 is hydrogen. The preferences for Y6, Y7 and Y9 are the same as set out for compounds of formula (I) except that Y6 cannot be methoxymethy 1.
The compounds in Tables 1 to 35 below illustrate the compounds of the invention according tothe embodiment (F)
Table 1 :
Table 1 provides 24 compounds of formula (la) wherein Q is 2,6-dimethyl-4- alues listed in the table below.
Figure imgf000167_0001
Compound numbers R
1.01 methyl
1.02 ethyl
1.03 2-fluoro-ethyl
1.04 2-chloro-ethyl
1.05 2-bromo-ethyl
1.06 2-iodo-ethyl
1.07 2-cyano-ethyl
1.08 2,2-difluoro-ethyl
1.09 2,2-dichloro-ethyl
1.10 2,2,2-trifluoro-ethyl
1.11 2,2,2-trichloro-ethyl
1.12 2,2,2-tribromo-ethyl
1.13 n-propyl
1.14 3-fluoro-propyl
1.15 3-chloro-propyl
1.16 3 -bromo -propyl Compound numbers R
1.17 1 ,2-difluoro-prop-2-yl
1.18 1 ,3-difluoro-prop-2-yl
1.19 1 ,3-dichloro-prop-2-yl
1.20 1 -chloro-3-fluoro-prop-2-yl
1.21 3 ,3 ,3 -trifluoro-propyl
1.22 n-butyl
1.23 4,4,4-trifluoro-butyl
1.24 Vinyl
Table 2:
Table 2 provides 24 compounds of formula (la) wherein Q is 2-ethyl-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 3:
Table 3 provides 24 compounds of formula (la) wherein Q is 2,6-diethyl-4-(heptafluoroprop- 2-yl)-phenyl and R1 has the values listed in Table 1.
Table 4:
Table 4 provides 24 compounds of formula (la) wherein Q is 2-methoxymethyl-6-methyl-4- (heptafluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 5:
Table 5 provides 24 compounds of formula (la) wherein Q is 2-bromo-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 6:
Table 6 provides 24 compounds of formula (la) wherein Q is 2-bromo-6-ethyl-4-(hepta- fluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 7:
Table 7 provides 24 compounds of formula (la) wherein Q is 2,6-dichloro-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 8:
Table 8 provides 24 compounds of formula (la) wherein Q is 2,6-dibromo-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 9: Table 9 provides 24 compounds of formula (la) wherein Q is 2,6-dimethyl-4-(nonafluorobut- 2-yl)-phenyl and R1 has the values listed in Table 1.
Table 10:
Table 10 provides 24 compounds of formula (la) wherein Q is 2-ethyl-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 11 :
Table 11 provides 24 compounds of formula (la) wherein Q is 2,6-diethyl-4-(nonafluorobut- 2-yl)-phenyl and R1 has the values listed in Table 1.
Table 12:
Table 12 provides 24 compounds of formula (la) wherein Q is 2-methoxymethyl-6-methyl-4- (nonafluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 13:
Table 13 provides 24 compounds of formula (la) wherein Q is 2-bromo-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 14:
Table 14 provides 24 compounds of formula (la) wherein Q is 2-bromo-6-ethyl-4-(nona- fluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 15:
Table 15 provides 24 compounds of formula (la) wherein Q is 2,6-dichloro-4-(nonafluoro- but-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 16:
Table 16 provides 24 compounds of formula (la) wherein Q is 2,6-dibromo-4-(nonafluoro- but-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 17:
Table 17 provides 24 compounds of formula (la') wherein Q is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Figure imgf000169_0001
Table 18: Table 18 provides 24 compounds of formula (la') wherein Q is 2-ethyl-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 19:
Table 19 provides 24 compounds of formula (la') wherein Q is 2,6-diethyl-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 20:
Table 20 provides 24 compounds of formula (la') wherein Q is 2-methoxymethyl-6-methyl- 4-(heptafluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 21 :
Table 21 provides 24 compounds of formula (la') wherein Q is 2-bromo-6-methyl-4-(hepta- fluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 22:
Table 22 provides 24 compounds of formula (la') wherein Q is 2-bromo-6-ethyl-4-(hepta- fluoroprop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 23:
Table 23 provides 24 compounds of formula (la') wherein Q is 2,6-dichloro-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 24:
Table 24 provides 24 compounds of formula (la') wherein Q is 2,6-dibromo-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 25:
Table 25 provides 24 compounds of formula (la') wherein Q is 2,6-dimethyl-4-(nonafluoro- but-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 26:
Table 26 provides 24 compounds of formula (la') wherein Q is 2-ethyl-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 27:
Table 27 provides 24 compounds of formula (la') wherein Q is 2,6-diethyl-4-(nonafluorobut- 2-yl)-phenyl and R1 has the values listed in Table 1.
Table 28:
Table 28 provides 24 compounds of formula (la') wherein Q is 2-methoxymethyl-6-methyl- 4-(nonafluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 29: Table 29 provides 24 compounds of formula (la') wherein Q is 2-bromo-6-methyl-4-(nona- fluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 30:
Table 30 provides 24 compounds of formula (la') wherein Q is 2-bromo-6-ethyl-4-(nona- fluorobut-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 31 :
Table 31 provides 24 compounds of formula (la') wherein Q is 2,6-dichloro-4-(nonafluoro- but-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 32:
Table 32 provides 24 compounds of formula (la') wherein Q is 2,6-dibromo-4-(nonafluoro- but-2-yl)-phenyl and R1 has the values listed in Table 1.
Table 33:
Table 33 provides 24 compounds of formula (lb) wherein Q is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Figure imgf000171_0001
Table 34:
Table 34 provides 24 compounds of formula (Ic) wherein Q is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Figure imgf000171_0002
Table 35:
Table 35 provides 24 compounds of formula (Id) wherein Q is 2,6-dimethyl-4-(heptafluoro- prop-2-yl)-phenyl and R1 has the values listed in Table 1.
Figure imgf000172_0001
The following Examples illustrate, but do not limit, the invention according to the embodiment (F):
3-amino-4-cyano-N-[2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)-phenyl]- benzamide (Compound No. Al of Table A)
3-amino-5-cyano-N-[2,6-dimethyl-4-(l,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)-phenyl]- benzamide (Compound No. Bl of Table B)
Or a compound according toi Table A or Table B or Table C or Table D: Table A: Compounds of formula (la):
Figure imgf000172_0002
Figure imgf000173_0001
Figure imgf000174_0001
Figure imgf000175_0001
phenyl-
Table B: Compounds of formula (lb):
Figure imgf000175_0002
Figure imgf000175_0004
Table C: Compounds of formula (Ic):
Figure imgf000175_0003
Figure imgf000176_0001
Table D: Compounds of formula (Id):
Figure imgf000176_0002
Figure imgf000176_0004
In an embodiment (H), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000176_0003
wherein
A1, A2, A3 and A4 are independently of one another C-X or nitrogen, provided that than two of A1, A2, A3 and A4 are nitrogen; each X is independently hydrogen, halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl or Ci- C4alkoxy;
R1 and R2 are independently of one another hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl-; G1 and G2 are independently of one another oxygen or sulfur;
Q1 is aryl or aryl substituted by one to five substituents R3, which may be the same or different, or Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R3, which may be the same or different;
Q2 is aryl or aryl substituted by one to five substituents R4, which may be the same or different, or Q2 is heterocyclyl or heterocyclyl substituted by one to five substituents R4, which may be the same or different;
each R3 is independently halogen, cyano, nitro, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, hydroxy, Ci-C3alkoxy, Ci-Cshaloalkoxy, Ci-C3alkylthio-, Ci-Cshaloalkylthio-, Ci-C3alkyl- sulfinyl-, Ci-C3haloalkylsulfinyl-, Ci-C3alkylsulfonyl-, Ci-C3haloalkylsulfonyl-, N-C\- C4alkylamino-, N,N-di-(Ci-C4alkyl)amino-, Ci-C4alkylcarbonyl-, Ci-C4alkylcarbonyloxy-, Ci-C4alkoxycarbonyl-, Ci-C4alkylcarbonylamino- or phenyl;
each R4 is independently halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl, C2- C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-Cehalocycloalkyl, hydroxy, Ci-C3alkoxy or Ci-C3haloalkoxy;
R5 is Ci-C4perfluoroalkyl;
Y1 and Y4 are independently of each other halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, d- C4alkoxy-Ci-C4alkyl-, Ci-C3alkylthio-, Ci-C3haloalkylthio-, Ci-C3alkylsulfinyl-, Ci- C3haloalkylsulfinyl-, Ci-C3alkylsulfonyl- or Ci-C3haloalkylsulfonyl-; and
Y2 and Y3 are independently of each other hydrogen, halogen or Ci-C4alkyl;
or a salt or N-oxide thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (G) the preferred values of A1, A2, A3, A4, X, R1, R2, R5, G1, G2, Q1, Q2, Y1, Y2, Y3 and Y4 are, in any combination, as set out below.
Preferably A1 is C-X.
Preferably A2 is C-X.
Preferably A3 is C-X. Preferably A4 is C-X.
Preferably each X is independently hydrogen, halogen, cyano, methyl,
trifluoromethyl or methoxy, more preferably each X is independently hydrogen, fluoro, cyano, trifluoromethyl or methoxy, even more preferably each X is hydrogen, fluoro or cyano, yet even more preferably each X is hydrogen or fluoro, most preferably each X is hydrogen.
Preferably R1 is hydrogen, methyl, ethyl or acetyl, more preferably hydrogen, methyl or ethyl, even more preferably hydrogen or methyl, most preferably hydrogen.
Preferably R2 is hydrogen, methyl, ethyl or acetyl, more preferably hydrogen, methyl or ethyl, even more preferably hydrogen or methyl, most preferably hydrogen.
Preferably R5 is trifluoromethyl.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably Q1 is aryl or aryl substituted by one to five substituents R3, which may be the same or different, or Q1 is heteroaryl or heteroaryl substituted by one to five substituents R3, which may be the same or different, more preferably phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl, even more preferably phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl, most preferably phenyl or pyridyl substituted by one or two substituents independently selected from chloro, fluoro or methyl.
Preferably Q2 is aryl or aryl substituted by one to five substituents R4, which may be the same or different, or Q2 is heteroaryl or heteroaryl substituted by one to five substituents R4, which may be the same or different, more preferably Q2 is phenyl or pyridyl, or phenyl or pyridyl substituted by one to three substituents independently selected from hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl or methoxy, even more preferably Q2 is phenyl or pyridyl, or phenyl or pyridyl substituted by one or two substituents independently selected from chloro, fluoro, methyl, trifluoromethyl or methoxy. Preferably Y1 is halogen, cyano, methyl, ethyl, methoxymethyl or trifluoromethyl, more preferably bromo, chloro, cyano, methyl, ethyl, methoxymethyl or trifluoromethyl, even more preferably bromo, methyl or ethyl, yet even more preferably methyl or ethyl, most preferably methyl.
Preferably Y2 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen.
Preferably Y3 is hydrogen, fluoro, chloro or methyl, most preferably hydrogen.
Preferably Y4 is halogen, cyano, methyl, ethyl or trifluoromethyl, more preferably bromo, chloro, cyano, methyl, ethyl or trifluoromethyl, even more preferably bromo, methyl or ethyl, yet even more preferably methyl or ethyl, most preferably methyl.
A preferred embodiment of the embodiment (G) are compounds of formula (la) wherein A1, A2, A3, A4 are CH.
A preferred embodiment of the embodiment (G) are compounds of formula (lb) wherein A1 is C-F, and A2, A3, and A4 are CH.
A preferred embodiment of the embodiment (G) are compounds of formula (Ic) wherein A2 is C-F, and A1, A3, and A4 are CH.
A preferred embodiment of the embodiment (G) are compounds of formula (Id) wherein A3 is C-F, and A1, A2, and A4 are CH.
A preferred embodiment of the embodiment (G) are compounds of formula (Ie) wherein A4 is C-F, and A1, A2, and A3 are CH.
A preferred embodiment of the embodiment (G) are compounds of formula (If) wherein A1 is C-CN, and A2, A3, and A4 are CH.
The compounds in Tables 1 to 36 below illustrate the compounds of the invention according to the embodiment (G).
Table 1 :
Table 1 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is
1 2 2 3 1 4 2 trifluoromethyl, G and G are oxygen, Y and Y are hydrogen, Y and Y are methyl, Q is 4-methoxy-phenyl-, and Q1 has the values listed below.
Figure imgf000180_0001
Compound Q
numbers
1.01 5 -bromo-furan-2-yl
1.02 2-bromo-phenyl
1.03 5-bromo-pyrid-3-yl
1.04 2-chloro-4-fluoro-phenyl
1.05 3-chloro-2-fluoro-phenyl,
1.06 5 -chloro-2-fluoro-phenyl
1.07 3 -chloro-2-methyl-phenyl
1.08 2-chloro-4-nitro-phenyl
1.09 2-chloro-5 -nitro-phenyl
1.10 2-chloro-phenyl
1.1 1 3-chloro-phenyl
1.12 2-chloro-pyrid-3-yl
1.13 2-chloro-pyrid-4-yl
1.14 6-chloro-pyrid-3-yl
1.15 5-chloro-thiophen-2-yl
1.16 3 -chloro-5 -trifluoromethyl -pyrid-2-yl
1.17 4-cyano-2-fluoro-phenyl,
1.18 4-cyano-phenyl Compound Q
numbers
1.19 2,5 -dichloro -phenyl
1.20 2,3 -difluoro-phenyl
1.21 1 ,3-dimethyl-lH-pyrazol-5-yl
1.22 2-fluoro-phenyl
1.23 4-fluoro-phenyl
1.24 2-fluoro-pyrid-3 -yl
1.25 2-fluoro-3 -trifluoromethyl-phenyl
1.26 2-fluoro-5 -trifluoromethyl-phenyl
1.27 4-fluoro-3 -trifluoromethyl-phenyl
1.28 furan-2-yl
1.29 2-methoxy-phenyl
1.30 2-methyl-phenyl
1.31 3 -methyl-pyrid-2-yl
1.32 4-methyl- 1 ,2,3-thiadiazol-5-yl
1.33 4-nitro-phenyl
1.34 phenyl
1.35 1 ,2,3-thiadiazol-4-yl
1.36 thiophen-2-yl
1.37 2-trifluoromethoxy-phenyl
1.38 4-trifluoromethoxy-phenyl
1.39 2-trifluoromethyl-phenyl
1.40 4-trifluoromethyl-phenyl
Table 2:
Table 2 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G1 and G2 are oxygen, Y2 and Y3 are hydrogen, Y1 and Y4 are methyl, Q 4-trifluoromethyl-phenyl-, and Q1 has the values listed in Table 1.
Table 3:
Table 3 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G1 and G2 are oxygen, Y2 and Y3 are hydrogen, Y1 and Y4 are methyl, Q 4-chloro-phenyl-, and Q1 has the values listed in Table 1.
Table 4:
Table 4 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 5:
Table 5 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 6:
Table 6 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is phenyl-, and Q1 has the values listed in Table 1.
Table 7:
Table 7 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 8:
Table 8 provides 40 compounds of formula (la), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are bromo, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 9:
Table 9 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-methoxy-phenyl-, and Q1 has the values listed in Table 1.
G1
(lb) Table 10:
Table 10 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-trifluoromethyl -phenyl-, and Q1 has the values listed in Table 1.
Table 11 :
Table 11 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-chloro-phenyl-, and Q1 has the values listed in Table 1.
Table 12:
Table 12 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 13:
Table 13 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is
1 2 2 3 1 4 2 trifluoromethyl, G and G are oxygen, Y and Y are hydrogen, Y and Y are methyl, Q is 3-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 14:
Table 14 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is phenyl-, and Q1 has the values listed in Table 1.
Table 15:
Table 15 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 16:
Table 16 provides 40 compounds of formula (lb), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are bromo, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1. Table 17:
Table 17 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is -methoxy-phenyl-, and Q1 has the values listed in Table 1.
Figure imgf000184_0001
Table 18:
Table 18 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-trifluoromethyl -phenyl-, and Q1 has the values listed in Table 1.
Table 19:
Table 19 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-chloro-phenyl-, and Q1 has the values listed in Table 1.
Table 20:
Table 20 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 21 :
Table 21 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 22:
Table 22 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is phenyl-, and Q1 has the values listed in Table 1.
Table 23: Table 23 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 24:
Table 24 provides 40 compounds of formula (Ic), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are bromo, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 25:
Table 25 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is
1 2 2 3 1 4 2 trifluoromethyl, G and G are oxygen, Y and Y are hydrogen, Y and Y are methyl, Q is 4-methoxy-phenyl-, and Q1 has the values listed in Table 1.
Figure imgf000185_0001
Table 26:
Table 26 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is
1 2 2 3 1 4 2 trifluoromethyl, G and G are oxygen, Y and Y are hydrogen, Y and Y are methyl, Q is 4-trifluoromethyl -phenyl-, and Q1 has the values listed in Table 1.
Table 27:
Table 27 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-chloro-phenyl-, and Q1 has the values listed in Table 1.
Table 28:
Table 28 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 29:
Table 29 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is
3- fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 30:
Table 30 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is phenyl-, and Q1 has the values listed in Table 1.
Table 31 :
Table 31 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 32:
Table 32 provides 40 compounds of formula (Id), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are bromo, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 33:
Table 33 provides 40 compounds of formula (Ie), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G and G are oxygen, Y and Y are hydrogen, Y and Y are methyl, Q is - methoxy-phenyl-, and Q1 the values listed in Table 1.
Figure imgf000186_0001
Table 34:
Table 34 provides 40 compounds of formula (Ie), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-trifluoromethyl -phenyl-, and Q1 has the values listed in Table 1.
Table 35:
Table 35 provides 40 compounds of formula (Ie), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-chloro-phenyl-, and Q1 has the values listed in Table 1.
Table 36:
Table 36 provides 40 compounds of formula (le), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 37:
Table 37 provides 40 compounds of formula (le), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 38:
Table 38 provides 40 compounds of formula (le), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is phenyl-, and Q1 has the values listed in Table 1.
Table 39:
Table 39 provides 40 compounds of formula (le), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 40:
Table 40 provides 40 compounds of formula (le), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are bromo, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 41 :
Table 41 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is -methoxy-phenyl-, and Q1 the values listed in Table 1.
Figure imgf000188_0001
Table 42:
Table 42 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-trifluoromethyl -phenyl-, and Q1 has the values listed in Table 1.
Table 43:
Table 43 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-chloro-phenyl-, and Q1 has the values listed in Table 1.
Table 44:
Table 44 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 4-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 45:
Table 45 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3-fluoro-phenyl-, and Q1 has the values listed in Table 1.
Table 46:
Table 46 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is phenyl-, and Q1 has the values listed in Table 1.
Table 47: Table 47 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are methyl, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
Table 48:
Table 48 provides 40 compounds of formula (If), wherein R1 and R2 are hydrogen, R5 is trifluoromethyl, G 1 and G 2 are oxygen, Y 2 and Y 3 are hydrogen, Y 1 and Y 4 are bromo, Q 2 is 3,5-dichloro-phenyl-, and Q1 has the values listed in Table 1.
The following Examples illustrate, but do not limit, the invention according to the embodiment (G)
3-amino-N- {2,6-dimethyl-4-[2,2,2-trifluoro- 1 -(4-fluoro-phenyl)- 1 -hydroxy-ethyl] -phenyl} - benzamide (Compound B4 of Table B)
N- {2,6-bibromo-4-[ 1 -(3,5-dichloro-phenyl)-2,2,2-trifluoro- 1 -hydroxy-ethyl]-phenyl} -3- nitro-benzamide
3-benzoylamino-N-{2,6-dimethyl-4-[2,2,2-trifluoro-l-(4-fluoro-phenyl)-l-hydroxy-ethyl]- phenyl} -benzamide (Compound A20 of Table A)
3-[(4-cyanobenzoyl)-amino]-N-{2,6-dibromo-4-[l-(3,5-dichloro-phenyl)-2,2,2-trifluoro-l- hydroxy-ethyl]-phenyl} -benzamide (Compound A23 of Table A)
Or a copmpound according to the table A or table B or Table C or Table D:
Table A:
Compounds of formula (la')
Figure imgf000190_0001
Figure imgf000191_0001
Figure imgf000192_0001
phenyl-
Table B:
Compounds of formula (Ila')
Figure imgf000192_0002
Figure imgf000193_0001
phenyl-
Table C:
Compounds of formula (IVa')
Figure imgf000193_0002
Figure imgf000194_0001
phenyl-
Table D:
Compounds of formula (Va')
Figure imgf000194_0002
Figure imgf000195_0001
In an embodiment (G), the invention relates to a pharmaceutical composition comprising at least one compound of formu
Figure imgf000195_0002
wherein
A1, A2, A3 and A4 are independently of one another C-R5, C-R6 or nitrogen, provided that at least one of A1, A2, A3 and A4 is C-R5 and no more than two of A1, A2, A3 and A4 are nitrogen;
G1 and G2 are independently of each other oxygen or sulfur;
R1 and R2 are independently of each other hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl; R3 is hydrogen, Ci-C6alkyl, Ci-C6haloalkyl, C3-C6cycloalkyl-Ci-C4-alkyl-, Ci-C4alkoxy-Ci- C4-alkyl-, Ci-C4haloalkoxy-Ci-C4-alkyl-, Ci-C4alkylthio-Ci-C4-alkyl-, Ci-C4haloalkylthio- Ci-C4-alkyl-, C3-Cscycloalkyl, C3-Cshalocycloalkyl, phenyl or phenyl substituted by one to five substituents R7, which may be the same or different, 2-naphthyl or 2-naphthyl substituted by one to five substituents R7, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R7, which may be the same or different;
R4 is hydrogen, halogen, cyano, Ci-C6alkyl, Ci-C6haloalkyl, C3-C6cycloalkyl-Ci-C4-alkyl-, Ci-C4alkoxy-Ci-C4-alkyl-, Ci-C4haloalkoxy-Ci-C4-alkyl-, Ci-C4alkylthio-Ci-C4-alkyl-, C C4haloalkylthio-C i -C4-alkyl-, C i -C4alkylsulfinyl-C i -C4-alkyl-, C i -C4haloalkylsulfinyl-C i - C4alkyl-, Ci-C4-alkylsulfonyl-Ci-C4-alkyl-, Ci-C4haloalkylsulfonyl-Ci-C4-alkyl-, C3- C8cycloalkyl, C3-C8halocycloalkyl, Ci-C6alkoxy, Ci-C6haloalkoxy, Ci-C6alkylthio, Ci- C6haloalkylthio, Ci-C6alkylsulfinyl, Ci-C6haloalkylsulfinyl, Ci-C6alkylsulfonyl, Ci- Cehaloalkylsulfonyl, N,N-di(Ci-C6)alkylamino, phenyl or phenyl substituted by one to five substituents R8, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R8, which may be the same or different;
each R5 is independently cyano, thiocyanato, aminothiocarbonyl, N-Ci-C4alkyl-amino- thiocarbonyl or N,N-di-Ci-C4alkyl-aminothiocarbonyl;
each R6 is independently hydrogen, halogen, Ci-C4alkyl, Ci-C4haloalkyl or Ci-C4alkoxy; Q1 is aryl or aryl substituted by one to five substituents R9, which may be the same or different, or Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R9, which may be the same or different;
Y1 and Y4 are independently of each other hydrogen, cyano, halogen, Ci-C4alkyl, Ci- C4haloalkyl, Ci-C4alkoxy-Ci-C4-alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci- C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y2 and Y3 are independently of each other hydrogen, halogen or Ci-C4alkyl; and
each R7, R8 and R9 is independently cyano, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4halo- alkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl, C3-Cehalocycloalkyl, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci- C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, Ci- C4alkylamino, di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, C\- C4alkoxycarbonyl, Ci-C4alkylcarbonylamino or phenyl;
or a salt or N-oxide thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (H) the preferred values of A1, A2, A3, A4, G1, G2, R1, R2, R3, R4, R5, R6, R7, R8, R9, Q1, Y1, Y2, Y3 and Y4 are, in any combination, as set out below.
Preferably A1 is C-R5 or C-R6.
Preferably A2 is C-R5 or C-R6.
Preferably A3 is C-R5 or C-R6.
Preferably A4 is C-R5 or C-R6. Preferably one, two or three of A1, A2, A3 and A4 are C-R5, more preferably one or two of A1, A2, A3 and A4 are C-R5, most preferably one of A1, A2, A3 and A4 is C-R5.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably R1 is hydrogen, methyl, ethyl or acetyl, more preferably hydrogen, methyl or ethyl, even more preferably hydrogen or methyl, most preferably hydrogen.
Preferably R2 is hydrogen, methyl, ethyl or acetyl, more preferably hydrogen, methyl or ethyl, even more preferably hydrogen or methyl, most preferably hydrogen.
Preferably R3 is Ci-C6alkyl, Ci-C6haloalkyl, phenyl or phenyl substituted by one to five substituents R7, which may be the same or different, more preferably R3 is Ci-C6alkyl or Ci-C6haloalkyl, most preferably R3 is trifluoromethyl.
Preferably R4 is Ci-C6alkyl, Ci-C6haloalkyl, phenyl or phenyl substituted by one to five substituents R8, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents R8, which may be the same or different.
More preferably R4 is phenyl or phenyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-Cshaloalkoxy, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-Cshalo- alkoxy, which may be the same or different.
Even more preferably R4 is phenyl or phenyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-Cshaloalkoxy, which may be the same or different, or heterocyclyl or heterocyclyl substituted by one to five substituents selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C3alkoxy or Ci-C3halo- alkoxy, which may be the same or different. Examples of such groups for R4 are 4-bromo- phenyl, 4-chloro-phenyl, 4-cyano-phenyl, 3,4-dichloro-phenyl, 4-dif uoromethoxy-phenyl, 4- fluoro-phenyl, 4-methylsulfonyloxy-phenyl, 4-methylsulfonyl-phenyl, 4-methylthio-phenyl, 4-nitro-phenyl, phenyl, 4-trifluoromethoxy-phenyl and 4-trifluoromethyl-phenyl.
Most preferably R4 is phenyl or phenyl substituted by one substituent selected from halogen, Ci-C4alkyl, Ci-C4haloalkyl. Examples of such preferred groups for R4 are 4-chloro- phenyl, 4-fluoro-phenyl and 4-trifluoromethyl-phenyl.
Preferably each R5 is independently cyano, thiocyanato or aminothiocarbonyl, more preferably each R5 is independently cyano or thiocyanato, most preferably each R5 is cyano. Preferably each R6 is independently hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl or methoxy, more preferably hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl, even more preferably hydrogen, fluoro, methyl or trifluoromethyl, et even more preferably hydrogen or fluoro, most preferably hydrogen.
Preferably each R7 is independently cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl,
methylsulfonyl or phenyl.
Preferably each R8 is independently cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl,
methylsulfonyl or phenyl.
Preferably each R9 is independently cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl,
methylsulfonyl or phenyl.
Preferably Q1 is aryl or aryl substituted by one to five substituents R9, which may be the same or different, or Q1 is heteroaryl or heteroaryl substituted by one to five substituents R9, which may be the same or different.
More preferably Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl, even more preferably phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl, yet even more preferably phenyl or pyridyl, or phenyl or pyridyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfmyl, methylsulfonyl or phenyl, most preferably phenyl substituted by one or two substituents selected from chloro, fluoro or methyl. A particularly preferred group of compounds are compounds of formula (I) wherein Q1 is aryl or aryl substituted by one to five substituents R9, which may be the same or different.
Preferably Q1 is phenyl or phenyl substituted by one to four substituents
independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl, more preferably phenyl or phenyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl, even more preferably phenyl or phenyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl.
Another particularly preferred group of compounds are compounds of formula (I) wherein Q1 is heterocyclyl or heterocyclyl substituted by one to five substituents R9, which may be the same or different. The heterocyclyl group is preferably a heteroaryl group.
Preferably Q1 is pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl, more preferably pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl, or pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3-thiadiazolyl substituted by one to three substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl, even more preferably pyridyl or pyridyl substituted by one to two substituents independently selected from cyano, hydroxy, chloro, fluoro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl or phenyl, most preferably pyridyl substituted by one to two substituents independently selected from chloro, fluoro or methyl.
Preferably Y1 is cyano, halogen, methyl, ethyl, trifluoromethyl or methoxymethyl, more preferably cyano, bromo, chloro, methyl, ethyl, trifluoromethyl or methoxymethyl, even more preferably bromo, chloro, methyl, ethyl or methoxymethyl, yet even more preferably bromo, methyl or ethyl, even more preferably methyl or ethyl, most preferably methyl.
Preferably Y2 is hydrogen, chloro, fluoro or methyl, most preferably hydrogen. Preferably Y3 is hydrogen, chloro, fluoro or methyl, most preferably hydrogen.
Preferably Y4 is cyano, halogen, methyl, ethyl or trifluoromethyl, more preferably cyano, bromo, chloro, methyl, ethyl or trifluoromethyl, even more preferably bromo, chloro, methyl or ethyl, yet even more preferably bromo, methyl or ethyl, even more preferably methyl or ethyl, most preferably methyl.
One preferred embodiment of the embodiment (H) are compounds of formula (la) wherein A1 is C-CN, and A2, A3, A4 are CH.
Another preferred embodiment of the embodiment (H) are compounds of formula (lb) wherein A2 is C-CN, and A1, A3, and A4 are CH.
A further preferred embodiment of the embodiment (H) are compounds of formula
(Ic) wherein A3 is C-CN, and A1, A2, and A4 are CH.
Yet another preferred embodiment of the embodiment (H) are compounds of formula (Id) wherein A4 is C-CN, and A1, A2, and A3 are CH.
One preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- dimethy 1-pheny 1.
Another preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2-ethyl-6- methy 1-pheny 1.
A further preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- diethy 1-pheny 1.
Yet another preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2- methoxymethyl-6-methyl-phenyl.
One preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- dimethy 1-pheny 1.
Another preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2-ethyl-6- methy 1-pheny 1. A further preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- diethyl-phenyl.
Yet another preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2- methoxymethyl-6-methyl -phenyl.
One preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2,6-dimethyl-phenyl.
Another preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2-ethyl-6-methyl-phenyl.
A further preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]- 2,6-diethyl-phenyl.
Yet another preferred embodiment of the embodiment (H) are compounds of formula (I) wherein Q2 is 4-[3-(4-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5- yl]-2-methoxymethyl-6-methyl-phenyl. The compounds in Tables 1 to 12 below illustrate the compounds of the invention according to the embodiment (H).
Table 1 :
Table 1 provides 40 compounds of formula (la) wherein R4 is 4-chloro-phenyl and Q1 has the values listed in the table below.
Figure imgf000202_0001
Compound numbers Q
1.01 5-bromo-furan-2-yl
1.02 2-bromo-phenyl
1.03 5 -bromo -pyrid-3 -yl
1.04 2-chloro-4-fluoro-phenyl
1.05 3-chloro-2-fluoro-phenyl,
1.06 5 -chloro-2-fluoro-phenyl
1.07 3 -chloro-2-methyl-phenyl
1.08 2-chloro-4-nitro-phenyl
1.09 2-chloro-5 -nitro-phenyl
1.10 2-chloro-phenyl
1.11 3-chloro-phenyl
1.12 2-chloro-pyrid-3-yl
1.13 2-chloro-pyrid-4-yl
1.14 6-chloro-pyrid-3-yl
1.15 5-chloro-thiophen-2-yl
1.16 3 -chloro-5 -trifluoromethyl-pyrid-2-yl
1.17 4-cyano-2-fluoro-phenyl
1.18 4-cyano-phenyl
1.19 2,5-dichloro-phenyl
1.20 2,3-difluoro-phenyl Compound numbers Q
1.21 1 ,3-dimethyl-lH-pyrazol-5-yl
1.22 2-fluoro-phenyl
1.23 4-fluoro-phenyl
1.24 2-fluoro-pyrid-3 -yl
1.25 2-fluoro-3 -trifluoromethyl -phenyl
1.26 2-fluoro-5 -trifluoromethyl -phenyl
1.27 4-fluoro-3 -trifluoromethyl -phenyl
1.28 furan-2-yl
1.29 2-methoxy-phenyl
1.30 2-methyl -phenyl
1.31 3 -methyl -pyrid-2-yl
1.32 4-methyl-l ,2,3-thiadiazol-5-yl
1.33 4-nitro-phenyl
1.34 phenyl
1.35 1 ,2,3-thiadiazol-4-yl
1.36 thiophen-2-yl
1.37 2-trifluoromethoxy-phenyl
1.38 4-trifluoromethoxy-phenyl
1.39 2-trifluoromethyl-phenyl
1.40 4-trifluoromethyl-phenyl
Table 2:
Table 2 provides 40 compounds of formula (la) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 3:
Table 3 provides 40 compounds of formula (la) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1.
Table 4:
Table 4 provides 40 compounds of formula (lb) wherein R4 is 4-chloro-phenyl and Q1 has the values listed in Table 1.
Figure imgf000204_0001
Table 5:
Table 5 provides 40 compounds of formula (lb) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 6:
Table 6 provides 40 compounds of formula (lb) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1.
Table 7:
Table 7 provides 40 compounds of formula (Ic) wherein R4 is 4-chloro-phenyl and Q1 has the values listed in Table 1.
Figure imgf000204_0002
Table 8:
Table 8 provides 40 compounds of formula (Ic) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 9:
Table 9 provides 40 compounds of formula (Ic) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1.
Table 10:
Table 10 provides 40 compounds of formula (Id) wherein R4 is 4-chloro-phenyl and Q1 has the values listed in Table 1.
Figure imgf000205_0001
Table 11 :
Table 11 provides 40 compounds of formula (Id) wherein R4 is 4-fluoro-phenyl and Q1 has the values listed in Table 1.
Table 12:
Table 12 provides 40 compounds of formula (Id) wherein R4 is 4-trifluoromethyl-phenyl and Q1 has the values listed in Table 1.
The following Examples illustrate, but do not limit, the invention according to the embodiment (H) and preferred compounds according to the embodiment (H) are
3-amino-N-{4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6- dimethy 1-pheny 1 } -4 -cy ano -benzamide
N-{4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6-dimethyl- phenyl}-4-cyano-3-(4-nitro-benzoylamino)-benzamide (Compound No. Al of Table A) Or compounds as described in the Table A:
Table A: Compounds of formula (la):
Figure imgf000206_0001
Figure imgf000208_0001
phenyl-
In an embodiment (I), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000208_0002
wherein
A1, A2, A3 and A4 are independently of each other C-H, C-R3, or nitrogen;
G1 and G2 are independently of each other oxygen or sulfur;
R1 is hydrogen, Ci-Csalkyl, Ci-Csalkylcarbonyl-, or Ci-Csalkoxycarbonyl-;
R2 is hydrogen, Ci-Csalkyl, Ci-Csalkylcarbonyl-, or Ci-Csalkoxycarbonyl-;
each R3 is independently halogen, cyano, nitro, Ci-C8alkyl, Ci-C8haloalkyl, Ci-C8alkoxy, Ci-
C8haloalkoxy, Ci-C8alkylcarbonyl-, or Ci-C8alkoxycarbonyl-;
L is a single bond, or Ci-C6alkylene; Q1 is Ci-Csalkyl or Ci-dalkyl substituted by one to five R4; or
Q1 is C3-Ci0cycloalkyl or C3-Ci0cycloalkyl substituted by one to five R5, or C3-Ci0cyclo- alkenyl or C3-Ci0cycloalkenyl substituted by one to five R5, or
Q1 is aryl or aryl substituted by one to five R6, heterocyclyl or heterocyclyl substituted by one to five R6, aryloxy or aryloxy substituted by one to five R6, or heterocyclyloxy or heterocyclyloxy substituted by one to five R6;
each R4 is independently halogen, hydroxy, Ci-dalkoxy, N-Ci-dalkylamino-, NN-di-(d-
C8alkyl)amino-, N-Ci-dalkylcarbonylamino-, or (HOS02)S-;
each R5 is independently halogen, hydroxy, Ci-dalkyl, or Ci-dalkoxycarbonyl-;
each R6 is independently halogen, cyano, nitro, Ci-dalkyl, Ci-dhaloalkyl, Ci-dalkoxy, Ci- dhaloalkoxy, Ci-dalkylthio-, Ci-dhaloalkylthio-, Ci-dalkylsulfinyl-, Ci-dhaloalkyl- sulfinyl-, Ci-dalkylsulfonyl-, Ci-dhaloalkylsulfonyl-, N-Ci-dalkylamino-, NN-di-(d- C8alkyl)amino-, N-Ci-dalkylcarbonylamino-, aryl or aryl substituted by one to five R7, heterocyclyl or heterocyclyl substituted by one to five R7, aryl-Ci-C4alkyl- or aryl-Ci- C4alkyl- wherein the aryl moitey is substituted by one to five R7, heterocyclyl-Ci-C4alkyl- or heterocyclyl-Ci-C4alkyl- wherein the heterocyclyl moitiey is substituted by one to five R7, aryloxy or aryloxy substituted by one to five R7, or heterocyclyloxy or heterocyclyloxy substituted by one to five R7;
each R7 is independently halogen, cyano, nitro, Ci-dalkyl, Ci-dhaloalkyl, Ci-dalkoxy, or Ci-Cshaloalkoxy; and
Q2 is a moiety of formula (II) or (III)
Figure imgf000209_0001
wherein
Y1 and Y5 are independently of each other halogen, cyano, Ci-Csalkyl, Ci-Cshaloalkyl, Ci- C4alkoxy-Ci-C4-alkyl-, d-Cgalkylthio-, Ci-C8haloalkylthio-, d-Cgalkylsulfinyl-, d- dhaloalkylsulfinyl-, Ci-Cgalkylsulfonyl-, or Ci-Cghaloalkylsulfonyl-;
Y3 is d-dperfluoroalkyl, Ci-Cgperfiuoroalkylthio-, Ci-Cgperfluoroalkylsulfinyl-, or d- Cgperfluoroalkylsulfonyl-;
Y2 and Y4 are independently of each other hydrogen, halogen, or Ci-dalkyl; Y6 and Y9 are independently of each other halogen, cyano, Ci-Csalkyl, Ci-Cshaloalkyl, Ci- C4alkoxy-Ci-C4-alkyl-, Ci-Csalkylthio-, Ci-Cshaloalkylthio-, Ci-Csalkylsulfmyl-, Q- Cshaloalkylsulfinyl-, Ci-Csalkylsulfonyl-, or Ci-Cshaloalkylsulfonyl-;
Y8 is C2-C8perfluoroalkyl, Ci-Csperfluoroalkylthio-, Ci-Csperfluoroalkylsulfinyl-, or Ci- Csperfluoroalkylsulfonyl-;
Y7 is hydrogen, halogen, or Ci-C8alkyl; or a salt or N-oxide thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans. In the embodiment (I) the preferred values of A1, A2, A3, A4, G1, G2, R1, R2, R3, L,
Q1, R4, R5, R6, R7, Q2, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, and Y9 are, in any combination, as set out below.
Preferably no more than two of A1, A2, A3 and A4 are nitrogen.
Preferably A1 is C-H or C-R3, most preferably A1 is C-R3.
Preferably A2 is C-H or C-R3, most preferably A2 is C-H.
Preferably A3 is C-H or C-R3, most preferably A3 is C-H.
Preferably A4 is C-H or C-R3, most preferably A4 is C-H.
Preferably G1 is oxygen.
Preferably G2 is oxygen.
Preferably R1 is hydrogen, methyl, ethyl, methylcarbonyl-, or methoxycarbonyl-, more preferably hydrogen, methyl, or ethyl, even more preferably hydrogen, or methyl, most preferably hydrogen.
Preferably R2 is hydrogen, methyl, ethyl, methylcarbonyl-, or methoxycarbonyl-, more preferably hydrogen, methyl, or ethyl, even more preferably hydrogen, or methyl, most preferably hydrogen.
Preferably each R3 is independently halogen, cyano, nitro, Ci-Csalkyl, or Ci-Cs- haloalkyl, more preferably halogen or Ci-Csalkyl, even more preferably Ci-Csalkyl, most preferably methyl.
Preferably L is a single bond, -CH2-, -CH2-CH2-, -CH(CH3)-, or -CH2-CH2-CH2-, more preferably single bond, -CH2-, or -CH2-CH2-, even more preferably single bond, or -CH2-, most preferably -CH2-. In a preferred embodiment Q1 is Ci-Csalkyl or Ci-Csalkyl substituted by one to five R4, preferably n-propyl or n-butyl, or n-propyl or n-butyl substituted by one to five R4, most preferably /? -propyl or /? -propyl substituted by one to five R4.
In a preferred embodiment Q1 is C3-Ciocycloalkyl or C3-Ciocycloalkyl substituted by one to five R5, or C3-Ciocycloalkenyl or C3-Ciocycloalkenyl substituted by one to five R5, more preferably C3-Ci0cycloalkyl or C3-Ci0cycloalkyl substituted by one to five R5, most preferably cyclohexyl or cyclohexyl substituted by one to five R5.
In a preferred embodiment Q1 is aryl or aryl substituted by one to five R6, heterocyclyl or heterocyclyl substituted by one to five R6, aryloxy or aryloxy substituted by one to five R6, or heterocyclyloxy or heterocyclyloxy substituted by one to five R6, most preferably Q1 is aryl or aryl substituted by one to five R6, heterocyclyl or heterocyclyl substituted by one to five R6 (wherein the heterocyclyl is pyridyl, imidazolyl, furanyl, isoxazolyl, thiophenyl, thiazolyl, thiadiazolyl, quinolinyl, indolyl, indazolyl, benzimidazolyl, benzothiazolyl, purinyl, pyrrolidinyl, tetrahydro-furanyl, [l,3]dioxolanyl, piperazinyl, morpholinyl, benzo[l,3]dioxolanyl, 2,3-dihydro-benzofuranyl, or 2,3-dihydro- benzo[l,4]dioxinyl), or aryloxy or aryloxy substituted by one to five R6.
In a preferred embodiment Q'-L- is aryl or aryl substituted by one to five R6, or heterocyclyl- or heterocyclyl- substituted by one to five R6, more preferably Q!-L- is aryl or aryl substituted by one to five R6, or heteroaryl- or heteroaryl- substituted by one to five R6 (wherein the heteroaryl is thiazolyl, quinolinyl, or purinyl).
In a preferred embodiment Q'-L- is aryl-Ci-C4alkyl- or aryl-Ci-C4alkyl- wherein the aryl moiety is substituted by one to five R6, or heterocyclyl-Ci-C4alkyl- or heterocyclyl-Ci- C4alkyl- wherein the heterocyclyl moiety is substituted by one to five R6, more preferably Q1 is aryl-CH2- or aryl-CH2- wherein the aryl moiety is substituted by one to five R6, heterocyclyl-CH2- or heterocyclyl-CH2- wherein the heterocyclyl moiety is substituted by one to five R6 (wherein the heterocyclyl is pyridyl, tetrahydro-furanyl, benzo[l,3]dioxolanyl, or 2,3-dihydro-benzo[l,4]dioxinyl), aryl-CH2-CH2- or aryl-CH2-CH2- wherein the aryl moiety is substituted by one to five R6, or heterocyclyl-CH2-CH2- or heterocyclyl-CH2-CH2- wherein the heterocyclyl moiety is substituted by one to five R6 (wherein the heterocyclyl is thiophenyl, indolyl, morpholinyl, or [l,3]dioxolanyl). It is particularly preferred when Q'-L- is pyridyl-CH2-, in particular pyrid-2-yl-CH2-. Preferably each R4 is independently halogen, hydroxy, Ci-C8alkoxy, N-Ci-C8alkyl- carbonylamino-, or (HOS02-S)-, more preferably halogen, hydroxy, or Ci-C8alkoxy, even more preferably chloro, fluoro, hydroxy, or methoxy, most preferably fluoro.
Preferably each R5 is independently halogen, hydroxy, or Ci-C8alkyl, more preferably hydroxy, or methyl, most preferably hydroxy.
Preferably each R6 is independently halogen, cyano, nitro, Ci-C8alkyl, Ci-C8halo- alkyl, Ci-C8alkoxy, Ci-C8haloalkoxy, Ci-C8alkylthio-, Ci-C8alkylsulfinyl-, Ci-C8alkyl- sulfonyl-, N,N-dimethylamino-, Ci-C8alkylcarbonyl-, Ci-C8alkoxycarbonyl-, aryl or aryl substituted by one to five R7, or heterocyclyl or heterocyclyl substituted by one to five R7, more preferably bromo, chloro, fluoro, cyano, nitro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio-, methylsulfinyl-, methylsulfonyl-, N,N-dimethylamino-, phenyl, pyrazolyl, or piperidinyl, most preferably chloro, fluoro, cyano, nitro, methyl, trifluoromethyl, methoxy, or trifluoromethoxy.
Preferably each R7 is independently halogen, cyano, nitro, Ci-C8alkyl, Ci- C8haloalkyl, Ci-C8alkoxy, or Ci-C8haloalkoxy, most preferably chloro, fluoro, cyano, nitro, methyl, trifluoromethyl, methoxy, or trifluoromethoxy.
Preferably Q2 is a moiety of formula (II).
Preferably Y1 is halogen, cyano, methyl, ethyl, trifluoromethyl, or methoxymethyl, more preferably bromo, chloro, methyl, ethyl, methoxymethyl, most preferably bromo, chloro, methyl, ethyl.
Preferably Y2 is hydrogen, chloro, fluoro, or methyl, most preferably hydrogen.
Preferably Y3 is heptafluoro-propyl, heptafluoro-prop-2-yl, heptafluoro-propylthio-, heptafluoro-propylsulfinyl-, heptafluoro-propylsulfonyl-, heptafluoro-prop-2-ylthio-, heptafluoro-prop-2-ylsulfinyl-, heptafluoro-prop-2-ylsulfonyl-, or nonafluoro-but-2-yl.
In one embodiment Y3 is C2-C6perfluoroalkyl, most preferably Y3 is heptafluoro- prop-2-yl or nonafluoro-but-2-yl.
Preferably Y4 is hydrogen, chloro, fluoro, or methyl, most preferably hydrogen.
Preferably Y5 is halogen, cyano, methyl, ethyl, or trifluoromethyl, most preferably bromo, chloro, methyl, or ethyl.
Preferably Y6 is halogen, cyano, methyl, ethyl, trifluoromethyl, or methoxymethyl, more preferably bromo, chloro, methyl, ethyl, or methoxymethyl, most preferably bromo, chloro, methyl, or ethyl.
Preferably Y7 is hydrogen, chloro, fluoro, or methyl, most preferably hydrogen. Preferably Y is heptafluoro-propyl, heptafluoro-prop-2-yl, heptafluoro-propylthio-, heptafluoro-propylsulfmyl-, heptafluoro-propylsulfonyl-, heptafluoro-prop-2-ylthio-, heptafluoro-prop-2-ylsulfmyl-, heptafluoro-prop-2-ylsulfonyl-, or nonafluoro-but-2-yl.
In one embodiment Y8 is C2-C6perfluoroalkyl, most preferably Y8 is heptafluoro- prop-2-yl or nonafluoro-but-2-yl.
Preferably Y9 is halogen, cyano, methyl, ethyl, trifluoromethyl, or methoxymethyl, more preferably bromo, chloro, methyl, ethyl, or methoxymethyl, most preferably bromo, chloro, methyl, or ethyl.
In a preferred embodiment Q2 is 2-ethyl-6-methyl-4-(heptafluoro-prop-2-yl)-phenyl. In a preferred embodiment Q2 is 2-bromo-6-methyl-4-(heptafluoro-prop-2-yl)- phenyl.
In a preferred embodiment Q2 is 2-bromo-6-ethyl-4-(heptafluoro-prop-2-yl)-phenyl.
In a preferred embodiment Q2 is 2,6-dichloro-4-(heptafluoro-prop-2-yl)-phenyl.
In a preferred embodiment Q2 is 2,6-dibromo-4-(heptafluoro-prop-2-yl)-phenyl. In a preferred embodiment Q2 is 2-bromo-6-chloro-4-(heptafluoro-prop-2-yl)-phenyl.
In a preferred embodiment Q2 is 2-ethyl-6-methyl-4-(nonafluoro-but-2-yl)-phenyl.
In a preferred embodiment Q2 is 2-bromo-6-methyl-4-(nonafluoro-but-2-yl)-phenyl.
In a preferred embodiment Q2 is 2-bromo-6-ethyl-4-(nonafluoro-but-2-yl)-phenyl.
In a preferred embodiment Q2 is 2,6-dichloro-4-(nonafluoro-but-2-yl)-phenyl.
In a preferred embodiment Q2 is 2,6-dibromo-4-(nonafluoro-but-2-yl)-phenyl.
In a preferred embodiment Q2 is 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)-phenyl.
A preferred embodiment are compounds of formula (la) wherein A1 is C-Me, A2, A3,
4 1 2 1 2 1 2
A are CH, and G , G R , R\ Q1, L, and Qz are defined for a compound of formula (I). The preferences for G1, G2, R1, R2, Q1, L, and Q2 are the same as those defined for a compound of formula (I).
The compounds in Tables 1 to 12 below illustrate the compounds of the invention according to the embodiment (I) Table 1 :
Table 1 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2-ethyl-6-methyl-4-(heptafluoro-prop-2-yl)-phenyl, and Q1, and L have the values listed in the table below.
Figure imgf000214_0001
Figure imgf000215_0001
Table 2:
Table 2 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2-bromo-6-methyl-4-(heptafluoro-prop-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 3 :
Table 3 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2-bromo-6-ethyl-4-(heptafluoro-prop-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 4:
Table 4 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2,6-dichloro-4-(heptafluoro-prop-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 5 :
Table 5 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2,6-dibromo-4-(heptafluoro-prop-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 6:
Table 6 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2-bromo-6-chloro-4-(heptafluoro-prop-2-yl)-phenyl, and Q1, and L have the values listed in Table 1. Table 7:
Table 7 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2-ethyl-6-methyl-4-(nonafluoro-but-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 8:
Table 8 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2-bromo-6-methyl-4-(nonafluoro-but-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 9:
Table 9 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2-bromo-6-ethyl-4-(nonafluoro-but-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 10:
Table 10 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2,6-dichloro-4-(nonafluoro-but-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 11 :
Table 11 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is 2,6-dibromo-4-(nonafluoro-but-2-yl)-phenyl, and Q1, and L have the values listed in Table 1.
Table 12:
Table 12 provides 30 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, Q2 is Q2 is 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)-phenyl, and Q , and L have the values listed in Table 1.
The following Examples illustrate, but do not limit, the invention according to the embodimanet (J) an the following compounds are preferred in the embodiment (I): N- 1 -butyl-N-4-[2,6-dimethyl-4-( 1 ,2,2,2-tetrafluoro- 1 -trifluoromethyl-ethyl)-phenyl]-2- methyl-terephthalamide (Compound No. Al of Table A)
N- 1 -L-Q 1 -N'-4-[2-ethyl-4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -trifluoromethyl-propyl)-6-methyl- phenyl]-2-methyl-terephthalamide
Or a compound as listed in the Table A
Table A:
Table A provides 107 compounds of formula (la) wherein G1 and G2 are both oxygen, R1 and R2 are both hydrogen, and Q1, L and Q2 have the values listed in the table below.
Figure imgf000217_0001
Figure imgf000218_0001
Figure imgf000219_0001
Figure imgf000220_0001
Figure imgf000221_0001
Figure imgf000222_0001
Figure imgf000223_0001
Figure imgf000224_0001
Figure imgf000225_0001
Figure imgf000226_0001
Figure imgf000227_0001
In an embodiment (J), the invention relates to a pharmaceutical composition comprising at least one compound of formula
Figure imgf000228_0001
wherein
Q1 is aryl or heterocyclyl, each optionally substituted by one to five R3 substituents, which may be the same or different;
Q2 is selected from
2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl,
2-bromo-6-chloro-4-(nonafluorobut-2-yl)phenyl,
2,6-dichloro-4-(nonafluoro-but-2-yl)phenyl,
2,6-dimethyl-4-(nonafluoro-but-2-yl)phenyl,
2-chloro-6-methoxymethyl-4-(nonafluorobut-2-yl)phenyl, and
2-bromo-6-methoxymethyl-4-(nonafluorobut-2-yl)phenyl;
R1 is selected from hydrogen, Ci-C8alkyl, Ci-C8alkylcarbonyl, Ci-C8alkoxycarbonyl and Ci-C4alkyl-C(0)NH2;
R2 is selected from hydrogen, Ci-Csalkyl, Ci-Csalkylcarbonyl, Ci-Csalkoxycarbonyl and Ci-C4alkyl-C(0)NH2; and
R3 is selected from cyano, nitro, halogen, hydroxyl, acetoxy, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, Ci-C4alkylthio, Ci-C4alkoxy-Ci-C4alkyl, Ci-C4alkoxy- Ci-C4alkoxy, CN-Ci-C4alkyl, Ci-C4alkyl-C(0)0, Ci-C4alkyl-S(0)2, NH2, Ci-C4alkylNH, (Ci-C4alkyl)2N, (Ci-C4alkylO)2P(0)0, phenyl and a five to six-membered monocyclic heterocycle containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur;
or an agrochemically acceptable salt or N-oxides thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans. In the embodiment (J) Preferred values of Q1, Q2, R1, R2 and R3 are, in any combination, as set out below.
Preferably, Q1 is aryl or heteroaryl; each optionally substituted by one to five R3 substituents, which may be the same or different.
More preferably, Q1 is selected from phenyl, biphenyl and a five to six-membered monocyclic heteroaryl group containing 1 , 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; each optionally substituted by one to five R3 substituents, which may be the same or different.
Yet more preferably, Q1 is selected from phenyl, biphenyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, benzothiadiazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl; each optionally substituted by one to five R3, and more preferably by one to three R3 substituents, which may be the same or different.
Even more preferably, Q1 is selected from phenyl, biphenyl, furanyl, pyridyl, thienyl, thiadiazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl and pyrimidinyl; each optionally substituted by one to three R3 substituents, which may be the same or different.
Preferably, R3 is selected from cyano, nitro, fluoro, chloro, bromo, iodo, hydroxyl, acetoxy, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, Ci-C4alkylthio, Ci-C4alkoxy-Ci-C4alkyl, Ci-C4alkoxy-Ci-C4alkoxy, CH2-CN, C(0)OCH3, S(0)2CH3, NH2, N(CH3)2, OP(0)(CH2CH3)2, phenyl, N-pyrroyl, thiadiazolyl, and pyridyl.
More preferably, R3 is selected from cyano, nitro, fluoro, chloro, bromo, iodo, hydroxyl, acetoxy, methyl, ethyl, isopropyl, tert-butyl, difiuoromethyl, trifiuoromethyl, methoxy, ethoxy, dif uoromethoxy, trifluoromethoxy, methylthio, isopropylthio, 3-ethoxy-n- propyl, methoxymethyl, 2 -methoxy ethoxy, CH2CN, C(0)OCH3, S(0)2CH3, NH2, N(CH3)2, OP(0)(CH2CH3)2, phenyl, N-pyrroyl, thiadiazolyl, and pyridyl.
Most preferably, R3 is selected cyano, nitro, bromo, chloro, fluoro, methyl, ethyl, trifiuoromethyl, methoxy and trifluoromethoxy. Most preferred Q1 are as herein-defined in the examples and compounds of Tables A to M.
Preferably, Q2 is selected from
2-ethyl-6-methyl-4-(nonafluoro-but-2-yl)phenyl,
2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl, and
2,6-dichloro-4-(nonafluoro-but-2-yl)phenyl.
Preferably, R1 is hydrogen. Preferably, R2 is hydrogen.
In a first preferred aspect, the present invention provides a compound of formula (I) wherein Q2 is 2-ethyl-6-methyl-4-(nonafluoro-but-2-yl)phenyl; and Q1, R1, R2 and R3 are defined herein.
In a preferred embodiment of the embodiment (J) of the first preferred aspect, the present invention provides a compound of formula (I) wherein
Q2 is 2-ethyl-6-methyl-4-(nonafluoro-but-2-yl)phenyl;
Q1 is selected from phenyl, biphenyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, benzothiadiazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl; each optionally substituted by one to three R3 substituents, which may be the same or different;
R1 and R2 are both hydrogen; and
R3 is selected from cyano, nitro, fluoro, chloro, bromo, iodo, hydroxyl, acetoxy, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methylthio, isopropylthio, 3-ethoxy-n-propyl, methoxymethyl, 2-methoxyethoxy, CH2-CN, C(0)OCH3, S(0)2CH3, NH2, N(CH3)2, OP(0)(CH2CH3)2, phenyl, N-pyrroyl, thiadiazolyl, and pyridyl.
In a more preferred embodiment of the embodiment (J) of the first preferred aspect, the present invention provides a compound of formula (I) wherein
Q2 is 2-ethyl-6-methyl-4-(nonafluoro-but-2-yl)phenyl; Q1 is selected from phenyl, biphenyl, furanyl, pyridyl, thienyl, thiadiazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl and pyrimidinyl; each optionally substituted by one to three R3 substituents, which may be the same or different;
R1 and R2 are both hydrogen; and
R3 is selected cyano, nitro, bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
In a second preferred aspect, the present invention provides a compound of formula (I) wherein Q2 is 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl; and Q1, R1, R2 and R3 are defined herein.
In a preferred embodiment of the embodiment (J) of the second preferred aspect, the present invention provides a compound of formula (I) wherein
Q2 is 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl;
Q1 is selected from phenyl, biphenyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, benzothiadiazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl; each optionally substituted by one to three R3 substituents, which may be the same or different;
R1 and R2 are both hydrogen; and
R3 is selected from cyano, nitro, fluoro, chloro, bromo, iodo, hydroxyl, acetoxy, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methylthio, isopropylthio, 3-ethoxy-n-propyl, methoxymethyl, 2-methoxyethoxy, CH2-CN, C(0)OCH3, S(0)2CH3, NH2, N(CH3)2, OP(0)(CH2CH3)2, phenyl, N-pyrroyl, thiadiazolyl, and pyridyl.
In a more preferred embodiment of the embodiment (J) of the second preferred aspect, the present invention provides a compound of formula (I) wherein
Q2 is 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl;
Q1 is selected from phenyl, biphenyl, furanyl, pyridyl, thienyl, thiadiazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl and pyrimidinyl; each optionally substituted by one to three R3 substituents, which may be the same or different;
R1 and R2 are both hydrogen; and R3 is selected cyano, nitro, bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
In a third preferred aspect, the present invention provides a compound of formula (I) wherein Q2 is 2,6-dichloro-4-(nonafluoro-but-2-yl)phenyl; and Q1, R1, R2 and R3 are defined wherein.
In a preferred embodiment of the embodiment (J) of the third preferred aspect, the present invention provides a compound of formula (I) wherein
Q2 is 2,6-dichloro-4-(nonafluoro-but-2-yl)phenyl;
Q1 is selected from phenyl, biphenyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, benzothiadiazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl; each optionally substituted by one to three R3 substituents, which may be the same or different;
R1 and R2 are both hydrogen; and
R3 is selected from cyano, nitro, fluoro, chloro, bromo, iodo, hydroxyl, acetoxy, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methylthio, isopropylthio, 3-ethoxy-n-propyl, methoxymethyl, 2-methoxyethoxy, CH2-CN, C(0)OCH3, S(0)2CH3, NH2, N(CH3)2, OP(0)(CH2CH3)2, phenyl, N-pyrroyl, thiadiazolyl, and pyridyl.
In a more preferred embodiment of the embodiment (J) of the third preferred aspect t, the present invention provides a compound of formula (I) wherein
Q2 is 2,6-dichloro-4-(nonafluoro-but-2-yl)phenyl;
Q1 is selected from phenyl, biphenyl, furanyl, pyridyl, thienyl, thiadiazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl and pyrimidinyl; each optionally substituted by one to three R3 substituents, which may be the same or different;
R1 and R2 are both hydrogen; and
R3 is selected cyano, nitro, bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
Most preferred compounds of formula (I) are selected from N-[2-ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)-6-methyl-phenyl]-3- (4-cyano-2-methylbenzoylamino)-2-methoxybenzamide (Compound No. A5 of Table A);
N-[2-ethyl-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-6-methylphenyl]-3-(4 fluoro-2-chlorobenzoylamino)-2-methoxybenzamide (Compound No. A3 of Table A);
N-[2-bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)phenyl]-3- (4-fluoro-2-chlorobenzoylamino)-2-methoxybenzamide (Compound No. B2 of Table B);
N-[2-bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-phenyl]-3- (4-cyano-2-methylbenzoylamino)-2-methoxybenzamide (Compound No. Bl of Table B);
N-[2,6-dichloro-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)phenyl] -3-(4- fluoro-2-chlorobenzoylamino)-2-methoxybenzamide (Compound No. CI of Table C);
N-[2,6-dichloro-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)phenyl] -3-(4- cyano-2-methylbenzoylamino)-2-methoxybenzamide (Compound No. C2 of Table C);
N-[2-ethyl-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-6-methylphenyl]-3-(4 fluorobenzoylamino)-2-methoxybenzamide (Compound No. Al of Table A);
N-[2-ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)-6-methyl-phenyl]-3- (4-cyanobenzoylamino)-2-methoxybenzamide (Compound No. A4 of Table A);
N-[2-ethyl-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-6-methylphenyl]-3-(2 methyl-3-nitrobenzoylamino)-2-methoxybenzamide (Compound No. A2 of Table A); and
N-{3-[2-Bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)- phenylcarbamoyl]-2-methoxyphenyl}-2,4,6-trifluorobenzamide (Compound No. B 189 of Table B). additional aspect the present invention provides a compound of formula (II),
Figure imgf000233_0001
wherein Q1, R1, R2 and R3 are as defined for formula (I) and the preferred embodiment of the embodiment (J)s thereof correspond to those of formula (I); and
Q2 is selected from: 2-ethyl-6-methyl-4-(perfluoroisopropyl)phenyl,
2-bromo-6-chloro-4-(perfluoroisopropyl)phenyl,
2,6-dichloro-4-(perfluoroisopropyl)phenyl,
2,6-dimethyl-4-(perfluoroisopropyl)phenyl, and
2-methyl-6-methoxymethyl-4-(perfluoroisopropyl)phenyl.
In a preferred embodiment of the embodiment (J), the present invention provides a compound of formula (II), wherein
Q1 is selected from phenyl, biphenyl, furanyl, pyridyl, thienyl, thiadiazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl and pyrimidinyl; each optionally substituted by one to three R3 substituents, which may be the same or different;
R1 and R2 are both hydrogen; and
R3 is selected cyano, nitro, bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy; and
Q2 is selected from:
2-ethyl-6-methyl-4-(perfluoroisopropyl)phenyl,
2-bromo-6-chloro-4-(perfluoroisopropyl)phenyl,
2,6-dichloro-4-(perfluoroisopropyl)phenyl,
2,6-dimethyl-4-(perfluoroisopropyl)phenyl, and
2-methyl-6-methoxymethyl-4-(perfluoroisopropyl)phenyl;
or an agrochemically acceptable salt or N-oxides thereof.
Most preferred compounds of the embodiment (J) are the compounds of formula (II) are those of Tables E, G, J, K and L.
The following compounds illustrate the compounds of the invention according to the embodiment (J)
N-[2-ethyl-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-6-methyl-phenyl]-3-(4-cyano- 2-methylbenzoylamino)-2-methoxybenzamide (Compound No. A5 of Table A) N-[2-ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)-6-methylphenyl]-3-(4-fluoro- 2-chlorobenzoylamino)-2-methoxybenzamide (Compound No. A3 of Table A)
N-[2-bromo-6-chloro-4-( 1 ,2,2,3 ,3 ,3 -hexafluoro- 1 -trifluoromethylpropyl)phenyl] -3-(4-fluoro
2- chlorobenzoylamino)-2-methoxybenzamide (Compound No. B2 of Table B)
N-[2-bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-phenyl]-3-(4- cyano-2-methylbenzoylamino)-2-methoxybenzamide (Compound No. Bl of Table B) N-[2,6-dichloro-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)phenyl] -3-(4-fluoro-2- chlorobenzoylamino)-2-methoxybenzamide (Compound No. CI of Table C)
N-[2,6-dichloro-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)phenyl] -3-(4-cyano-2- methylbenzoylamino)-2-methoxybenzamide (Compound No. C2 of Table C)
N-[2-ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)-6-methylphenyl]-3-(4- fluorobenzoylamino)-2-methoxybenzamide (Compound No. Al of Table A)
N-[2-ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)-6-methyl-phenyl]-3-(4- cyanobenzoylamino)-2-methoxybenzamide (Compound No. A4 of Table A)
N-[2-ethyl-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-6-methylphenyl]-3-(2 -methyl
3- nitrobenzoylamino)-2-methoxybenzamide (Compound No. A2 of Table A)
N-{3-[2-Bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)- phenylcarbamoyl]-2-methoxyphenyl}-2,4,6-trifluorobenzamide
And The compounds in Tables A to L below illustrate the compounds of the invention according to the embodiment (I)
Table A:
Figure imgf000236_0001
Comp. Q1
No.
Al 4-fluorophenyl
A2 2-methyl-3 -nitrophenyl
A3 2-chloro-4-fluorophenyl
A4 4-cyanophenyl
A5 4-cyano-2-methylphenyl
A6 2-chloropyrid-3 -yl
A7 2-fluoropyrid-3 -yl
A8 3-chlorophenyl
A9 2-chlorophenyl
A10 2-chloropyrid-4-yl
Al l 5-bromopyrid-3-yl
A12 5 -bromofuran-2-yl
A13 2-bromophenyl
A14 3 -chloro-5 -trifluoromethy lpyrid-2 -yl
A15 2-fiuoro-3 -trifluoromethylphenyl
A16 2,5-dichlorophenyl
A17 6-chloropyrid-3 -yl
A18 4-nitrophenyl
A19 phenyl
A20 2,3-difluorophenyl
A21 5 -chlorothiophen-2-yl Comp. Q
No.
A22 2-methyl-4-nitrophenyl
Table B:
Figure imgf000237_0001
Comp. Q
No.
Bl 4-cyano-2-methylphenyl
B2 2-chloro-4-fluorophenyl
B3 2-fluorophenyl
B4 2-methylphenyl
B5 2-chlorophenyl
B6 4-cyanophenyl
B7 4-nitrophenyl
B8 4-methylphenyl
B9 4-fluoro-2-methylphenyl
BIO 5 -chloro-2-fluorophenyl
Bl l 2-chloro-4-nitrophenyl
B12 furan-2-yl
B13 4-trifluoromethoxyphenyl
B14 4-fluoro-3 -trifluoro-methylphenyl
B15 4-trifluoromethylphenyl
B16 2-trifluoromethoxyphenyl Comp. Q
No.
B17 2-methoxyphenyl
B18 phenyl
B19 4-fluorophenyl
B20 2-trifluoromethylphenyl
B21 4-methyl-l ,2,3-thiadiazol-5-yl
B22 2,3 -difluorophenyl
B23 2 ,4 -difluorophenyl
B24 2-fluoro-5 -trifluoromethylphenyl
B25 4-isopropylphenyl
B26 4-methylsulfanylphenyl
B27 2,5 -dichlorophenyl
B28 4-methoxyphenyl
B29 2,4,5-trifluoro-3-chlorophenyl
B30 4-(pyrrol- 1 -yl)phenyl
B31 4-(l ,2,3-thiadiazol-4-yl)phenyl
B32 (3,4-dihydro-2H- benzo[b][l,4]dioxepine)-7-yl
B33 4-biphenyl
B34 3 -methylpyridin-2-yl
B35 2-fluoro-3 -trifluoromethylphenyl
B36 2-bromophenyl
B37 pyridin-3-yl
B38 4-methoxythiophen-3 -yl
B39 1 ,2,3-thiadiazol-4-yl
B41 5-phenyloxazol-4-yl
B42 2,5-dimethyl-2H-pyrazol-3-yl
B43 4-methyl-2-phenylpyrimidin-5-yl
B44 thiophen-2-yl
B45 2-methylsulfanylpyridin-3 -yl
B46 5-methyl-3-phenylisoxazol-4-yl Comp. Q
No.
B47 4-methyl-2-phenylthiazol-5-yl
B48 5-pyridin-2-ylthiophen-2-yl
B49 5 -phenylfuran-2-yl
B50 5 -methyl- 1 -phenyl- 1 H-pyrazol-4-yl
B51 6-morpholin-4-yl-pyrazin-2-yl
B52 5 -bromofuran-2-yl
B53 pyridin-2-yl
B54 pyridin-4-yl
B55 N-oxopyridin-3 -yl
B56 pyrazin-2-yl
B57 3 -bromothiophen-2-yl
B58 2,5-dimethylfuran-3-yl
B61 5-nitrofuran-2-yl
B62 2-chloro-5 -nitrophenyl
B63 2,5-dimethylfuran-3-yl
B64 2-nitro-4-chlorophenyl
B65 3 -methy 1-4 -bromopheny 1
B66 3 -chloropyridin-4-yl
B67 5 -chlorothiophen-2-yl
B68 3 -chloro-5 -iodophenyl
B69 2-methyl-3 -nitrophenyl
B70 3 -chloro-5 -trifluoromethylphenyl
B71 pyrimidin-2-yl
B72 2-chloro-5 -methylphenyl
B73 2-chloro-4,5 -difluorophenyl
B74 2-nitro-5 -methylphenyl
B75 2,6-dichloro-5-fiuoropyridin-3-yl
B76 4-bromo-2-ethyl-5 -methyl-2H- pyrazol-3-yl
B77 4-fiuoro-3 -nitrophenyl Comp. Q
No.
B78 2-pyridin-3 -ylthiazol-4-yl
B80 2-nitrophenyl
B81 2-trifluoromethylpyridin-3 -yl
B82 3 -methylpyridin-4-yl
B83 5 -bromo-2-chlorophenyl
B84 3 -bromo-4-methylphenyl
B85 2-bromo-3 -nitrophenyl
B86 2-methyl-3 ,5 -dinitrophenyl
B87 3 -methy 1-2 -nitrophenyl
B88 3 -methy lthiophen-2 -yl
B89 3 -methoxyisoxazol-5 -yl
B90 6-chloro- 1 -oxypyridin-2-yl
B91 2-hydroxy-3 ,5 -trichlorophenyl
B92 1 -methyl-5 -trifluoromethyl- 1 H- pyrazol-3-yl
B93 3 -chloro-2-methylpyridin-4-yl
B94 4-methyloxazol-5-yl
B95 2-methoxymethyl-4-methylthiazol-5- yl
B96 2 ,4 -dimethy lthiazol-5 -yl
B97 2,6-dichloropyridin-4-yl
B98 3 -methylisothiazol-4-yl
B99 2-methyl-3-carboxylic acid methyl ester-4-methylsulfanylphenyl
B100 1 ,5 -dimethyl- 1 H-pyrazol-3 -yl
B101 2-chloro-6-nitrophenyl
B102 4-chloro-2-fluoro-5 -nitrophenyl
B103 4-chloro-5 -difluoromethoxy- 1 -methyl - 1 H-pyrazol-3 -yl
B104 4-methyl-2-trifluoromethylthiazol-5-yl Comp. Q
No.
B105 2-chloro-4-methylthiazol-5 -yl
B106 2,3 -dichloro-4-(2-methoxy- ethoxy)phenyl
B107 5 -cyano-6-methylpyridin-2-yl
B108 2-methanesulfonyl-4- trifluoromethylphenyl
B109 2,4-dichloro-3-methoxyphenyl
B110 3 -cyanomethylphenyl
Bi l l pyrimidin-5-yl
B112 5 -tert-butyl-2-methyl-2H-pyrazol-3 -yl
B113 2-methyl-5 -trifluoromethyl-2H- pyrazol-3-yl
B114 2-chloro-4-methanesulfonyl-3- methoxyphenyl
B115 3-chloro-2-trifluoromethyl-pyridin-4- yl
B116 4-methylsulfanyl-2-nitrophenyl
B117 3 -cyano- 1 -methyl- 1 H-pyrazol-4-yl
B118 2-(2-chlorophenyl)-4-trifluoromethyl- thiazol-5-yl
B119 4-methanesulfonyl-3-methoxymethyl- 2-methylphenyl
B120 3 - [diethoxyphosphinyl)oxy]Phenyl
B121 2-isopropylsulfanylpyridin-3 -yl
B122 2-(3-ethoxypropyl)-6-trifluoromethyl- pyridin-3-yl
B123 4'-chloro-4-methylbiphenyl-3-yl
B124 thiophen-3-yl
B125 2-methylsulfanyl-4- trifluoromethylphenyl Comp. Q
No.
B126 4-trifluoromethylpyridin-5 -yl
B127 2-methyl-6-trifluoromethylpyridin-3- yi
B128 2,6-dichloronicotin-3-yl
B129 6-methoxy-3-bromo-2-methylphenyl
B130 2-chloro-4-fluoro-5 -nitrophenyl
B131 3 -difluoromethyl- 1 -methyl- 1 H- pyrazol-4-yl
B132 2-methoxypyridin-3 -yl
B133 4-chloro-2-methyl-5-trifluoromethyl -2H-pyrazol-3-yl
B134 2-methyl-4-trifluoromethylthiazol-5-yl
B135 2-chloro-4-bromophenyl
B136 4-chloro- 1 -methyl-5 -trifluoromethyl- lH-pyrazol-3-yl
B137 5 -methy lthiophen-2 -yl
B138 4-bromo-2-methylphenyl
B139 4-bromo-3-methoxy-2-methylphenyl
B140 5 -tert-butyl-2-methoxyphenyl
B141 3 -chloro-5 -trifluoromethylpyridin-2-yl
B142 5 -chloro- 1 ,3 -dimethyl- 1 H-pyrazol-4- yi
B143 4,5-dichloroisothiazol-3-yl
B144 5 -methy 1-2 -trifluoromethy lfuran-3 -yl
B145 3 -chlorothiophen-2-yl
B146 2-chloro-6-methoxypyridin-4-yl
B147 5 -chloro-4-methoxythiophen-3 -yl
B148 2-fluoro-5 -nitrophenyl
B149 3-chloro-2-fluoro-6- trifluoromethylphenyl Comp. Q
No.
B150 6-difiuoromethyl-2- methoxymethylpyridin-3 -yl
B151 2-fluoropyridin-4-yl
B152 1 -methyl-3 -trifluoromethyl- 1 H- pyrazol-4-yl
B153 2,5 -difluorophenyl
B154 2-chloro-5 -fluorophenyl
B155 2 ,4 -dichloropheny 1
B156 2-methyl-3 -chlorophenyl
B157 3 ,5 -dimethyl-isoxazol-4-yl
B158 2 ,6 -dichloropheny 1
B159 2-chloro-4-bromo-6-methylphenyl
B160 2-hydroxyl-3 ,5 -dichloroPhenyl
B161 2-iodo-3 -methyl-4-nitrophenyl
B162 2-bromo-3 -methyl-4-nitrophenyl
B163 2-chloro-3-methyl-4-nitrophenyl
B164 2 ,6 -dimethoxypheny 1
B165 3 ,5 -dimethyl-4-nitrophenyl
B166 2-methoxy-6-fiuorophenyl
B167 2-fiuoro-4-trifiuoromethylphenyl
B168 3 ,5 -difluorophenyl
B169 2,5 -difluorophenyl
B170 3 -chloro-4-nitrophenyl
B171 3 -acetate-4-nitrophenyl
B172 2 ,6 -difluorophenyl
B173 3 -ethoxy-4-nitrophenyl
B174 3 -amino-4-nitrophenyl
B175 3-(N,N-dimethylamino)-4-nitrophenyl
B176 2,6-difluoro-4-cyanophenyl
B177 2-methoxy-4-nitrophenyl Comp. Q
No.
B178 2-trifluoromethyl~4-nitrophenyl
B179 3 -trifluoromethyl-4-nitrophenyl
B180 2 ,4 -dinitropheny 1
B181 3 -hydroxyl-4-nitrophenyl
B182 2-chloro-4-methylphenyl
B183 2-chloro-3 -nitrophenyl
B184 2,3 -dichlorophenyl
B185 3 ,5 -dichloropyridin-2-yl
B186 2,5-dichlorothiophen-3-yl
B187 5 -bromopyrimidin-2-yl
B188 3 -trifluoromethylpyridin-2-yl
B189 2,4,6-trifluorophenyl
B190 3 -methy 1-4 -nitrophenyl
B191 2-fluoro-4-nitrophenyl
B192 3 -fluoro-4-nitrophenyl
B193 3 -nitrophenyl
B194 2-fluoro-pyridin-3 -yl
B195 3 ,4 -dinitropheny 1
B196 2-methyl-4-nitrophenyl
B197 2-fluoro-4- nitrophenyl
B198 2-chloro-4-cyanophenyl
B202 2-chloro-pyridin-3 -yl
B203 2-methoxy-4-cyano-6-hydroxyphenyl
B204 4-cyano-pyridin-3 -yl
B205 3 -fluoro-4-cyanophenyl
B206 3 -bromo-4-cyanophenyl
B207 3 -methoxy-4-nitrophenyl
B208 5-cyanopyridin-2-yl
B209 4-bromo-2,6-dichlorophenyl Comp. Q
No.
B210 2 ,4 -dichloropyrimidin-5 -yl
B211 2,4-dichloro-6-methylphenyl
B212 2-methyl-4-fluoro-5-nitrophenyl
B213 2-methyl-4-cyano-5-5-nitrophenyl
Table C:
Figure imgf000245_0001
Comp. Q
No.
CI 2-chloro-4-fluorophenyl
C2 4-cyano-2-methylphenyl
C3 2-fluorophenyl
C4 2-methylphenyl
C5 2-chlorophenyl
C6 4-cyanophenyl
C7 4-nitrophenyl
C8 4-methylphenyl
C9 4-fluoro-2-methylphenyl
CIO 5 -chloro-2-fluorophenyl
Cl l 2-chloro-4-nitrophenyl
C12 furan-2-yl
C13 4-trifluoromethoxyphenyl Comp. Q
No.
C14 4-fiuoro-3 -trifluoromethylphenyl
C15 4-trifluoromethylphenyl
C16 2-trifluoromethoxyphenyl
C17 2-methoxyphenyl
C18 phenyl
C19 4-fluorophenyl
C20 2-trifluoromethylphenyl
C21 4-methyl- 1 ,2,3-thiadiazol-5-yl
C22 2,3-difluorophenyl
C23 2,4-difluorophenyl
C24 2-fluoro-5 -trifluoromethylphenyl
C25 2-methyl-4-nitrophenyl
C26 2, 4-dichlorophenyl
C27 2, 3-dichlorophenyl
C28 3-nitrophenyl
C29 2-chloropyridine-3 -yl
C30 3,5-dimethylisoxazol-4-yl
C31 2-fluoro-4-cyanophenyl
C32 2-methyl-3 -chlorophenyl
C33 2,4,6-trifluorophenyl
C34 2-fluoropyridin-3 -yl
C35 3 -methyl-4-nitrophenyl
C36 2-fluoro-4-nitrophenyl
C37 3 -fluoro-4-nitrophenyl
C38 3 ,4-dinitrophenyl
C39 3 -hydroxy-4-nitrophenyl
C40 2-chloro-4-cyanophenyl
C41 3 -fluoro-4-cyanophenyl
C42 4-fluoro-3 -cyanophenyl Comp. Q
No.
C43 2-chloro-4-methylphenyl
C44 2-chloro-3 -nitrophenyl
Table D:
Figure imgf000247_0001
Comp. Q1 R1 No.
Dl phenyl Me
D2 phenyl Et
D3 4-cyanophenyl Me
D4 4-cyanophenyl Et
D5 4-fluoro-2chlorophenyl Me
D6 4-fluoro-2chlorophenyl Et
D7 2-fluorophenyl Me
D8 2-methylphenyl Me
D9 2-chlorophenyl Me
D10 4-methylphenyl Me
Dl l 4-fluoro-2-methylphenyl Me
D12 5 -chloro-2-fluorophenyl Me
D13 2-chloro-4-nitrophenyl Me
D14 furan-2-yl Me Comp. Q R No.
D15 4-trifiuoromethoxyphenyl Me
D16 4-fiuoro-3 -trifluoromethylphenyl Me
D17 4-trifluoromethylphenyl Me
D18 2-trifluoromethoxyphenyl Me
D19 2-methoxyphenyl Me
D2 4-fluorophenyl Me
D21 2-trifluoromethylphenyl Me
D22 4-methyl-l ,2,3-thiadiazol-5-yl Me
D23 2,3 -difluorophenyl Me
D24 2 ,4 -difluorophenyl Me
D25 2-fluoro-5 -trifluoromethylphenyl Me
D26 2-fluorophenyl Et
D27 2-methylphenyl Et
D28 2-chlorophenyl Et
D29 4-methylphenyl Et
D30 4-fluoro-2-methylphenyl Et
D31 5 -chloro-2-fluorophenyl Et
D32 2-chloro-4-nitrophenyl Et
D33 furan-2-yl Et
D34 4-trifluoromethoxyphenyl Et
D35 4-fluoro-3 -trifluoromethylphenyl Et
D36 4-trifluoromethylphenyl Et
D37 2-trifluoromethoxyphenyl Et
D38 2-methoxyphenyl Et
D39 4-fluorophenyl Et
D40 2-trifluoromethylphenyl Et
D41 2,3 -difluorophenyl Et
D42 2 ,4 -difluorophenyl Et
D43 2-fluoro-5 -trifluoromethylphenyl Et Comp. Q R No.
D44 2-chloro-4-cyanophenyl Me
D45 2-chloro-4-cyanophenyl Et
D46 4-nitrophenyl Me
D47 4-nitrophenyl Et
D48 2 ,6 -difluoropheny 1 Me
D49 2 ,6 -difluoropheny 1 Et
Table E:
Figure imgf000249_0001
Comp. Q RT No. (min)
El 2-fluorophenyl 4.27
E2 2-methylphenyl 4.13
E3 2-chlorophenyl 4.11
E4 4-cyanophenyl 3.87
E5 4-nitrophenyl 4.06
E6 4-methylphenyl 4.17
E7 4-fluoro-2-methylphenyl 4.12
E8 5 -chloro-2-fluorophenyl 4.46
E9 2-chloro-4-nitrophenyl 4.19
E10 furan-2-yl 3.87 El l 4-trifluoromethoxyphenyl 4.35
E12 4-fluoro-3-trifluoromethylphenyl 4.31
E13 4-trifluoromethylphenyl 4.3
E14 2-trifluoromethoxyphenyl 4.3
E15 2-methoxyphenyl 4.29
E16 phenyl 4
E17 4-fluorophenyl 4.04
E18 2-trifluoromethylphenyl 4.13
E19 2-chloro-4-fluorophenyl 4.16
E20 4-methyl-l ,2,3-thiadiazol-5-yl 3.81
E21 2,3-difluorophenyl 4.24
E22 2,4-difluorophenyl 4.31
E23 2-fluoro-5-trifluoromethylphenyl 4.48
E24 2,5-difluoro-4-cyanophenyl
E25 2-methyl-4-cyanophenyl 2.08
E26 3 -methyl -4-nitrophenyl 2.13
E27 2-methyl-4-nitrophenyl 2.11
E28 2,4,6-trifluorophenyl 2.11
E29 2,6-difluorophenyl 2.09
Table F:
(if)
Figure imgf000250_0001
Comp. Q
No.
Fl 2-fluorophenyl
F2 2-methylphenyl
F3 2-chlorophenyl
F4 furan-2-yl
F5 4-trifluoromethoxyphenyl
F6 3 -trifluoromethyl-4-fluorophenyl
F7 4-methyl-l,2,3-thiadiazol-5-yl
F8 2,3-difluorophenyl
F9 2,4-difluorophenyl
F10 2,4,6-trimethylphenyl
Fl l 2,3-dimethylphenyl
F12 2-fluoro-5 -chlorophenyl
F13 2-fluoro-4-chlorophenyl
F14 2-fluoro-4-trifluoromethylphenyl
F15 2,4-dichlorophenyl
F16 2-chloro-4-methanesulfonylphenyl
F17 3 ,4-dichlorophenyl
F18 4-methanesulfonylphenyl
F19 4-chlorophenyl
F20 3 -fluorophenyl
F21 3-cyanophenyl
F22 3 -methoxyphenyl
F23 3 -methyl-4-nitrophenyl
F24 2-methyl-4-nitrophenyl
F25 2,4,6-trifiuorophenyl
F26 4-trifiuoromethylphenyl
F27 2-methyl-4-fiuorophenyl
F28 2-chloro-4-nitrophenyl
F29 4-nitrophenyl 2-chloro-4-fluorophenyl
Table G:
Figure imgf000252_0001
Comp. Q
No.
Gl 2-methyl-4-cyanophenyl
G2 2-chloro-4-cyanophenyl
G3 2,4,6-trifluorophenyl
G4 2 ,6 -difluoro-4 -cy anopheny 1
G5 2-chloro-4-fluorophenyl
G6 2-fluorophenyl
G7 2-methylphenyl
G8 2-chlorophenyl
G9 4-cyanophenyl
G10 4-nitrophenyl
Gi l 4-methylphenyl
G12 4-fluoro-2-methylphenyl
G13 5 -chloro-2-fluorophenyl
G14 2-chloro-4-nitrophenyl
G15 furan-2-yl
G16 4-trifluoromethoxyphenyl
G17 4-fluoro-3 -trifluoromethylphenyl G18 4-trifluoromethylphenyl
G19 2-trifluoromethoxyphenyl
G20 2-methoxyphenyl
G21 phenyl
G22 4-fluorophenyl
G23 2-trifluoromethylphenyl
G24 4-methyl-l ,2,3-thiadiazol-5-yl
G25 2,3 -difluorophenyl
G26 2 ,4 -difluorophenyl
G27 2-f uoro-5 -trifluoromethylphenyl
Table H:
Figure imgf000253_0001
Comp. Q
No.
HI 2-methyl-4-cyanophenyl
H2 2,4,6-trifluorophenyl
H3 2-f uorophenyl
H4 2-methylphenyl
H5 2-chlorophenyl
H6 4-cyanophenyl
H7 4-nitrophenyl
H8 4-methylphenyl H9 4-fiuoro-2-methylphenyl
H10 5 -chloro-2-fiuorophenyl
Hl l 2-chloro-4-nitrophenyl
H12 furan-2-yl
H13 4-trifiuoromethoxyphenyl
H14 4-fiuoro-3 -trifluoromethylphenyl
H15 4-trifluoromethylphenyl
H16 2-trifluoromethoxyphenyl
H17 2-methoxyphenyl
H18 phenyl
H19 4-fluorophenyl
H20 2-trifluoromethylphenyl
H21 4-methyl-l,2,3-thiadiazol-5-yl
H22 2,3-difluorophenyl
H23 2,4-difluorophenyl
H24 2-fluoro-5 -trifluoromethylphenyl
H25 2-chloro-4-fluorophenyl
Table I:
Figure imgf000254_0001
Comp. Q
No.
11 2-methyl-4-cyanophenyl 12 2,4,6-trifiuorophenyl
13 2-fiuorophenyl
14 2-methylphenyl
15 2-chlorophenyl
16 4-cyanophenyl
17 4-nitrophenyl
18 4-methylphenyl
19 4-fiuoro-2-methylphenyl
110 5 -chloro-2-fiuorophenyl
111 2-chloro-4-nitrophenyl
112 furan-2-yl
113 4-trifiuoromethoxyphenyl
114 4-fiuoro-3 -trifluoromethylphenyl
115 4-trifiuoromethylphenyl
116 2-trifiuoromethoxyphenyl
117 2-methoxyphenyl
118 phenyl
119 4-fiuorophenyl
120 2-trifiuoromethylphenyl
121 4-methyl- 1 ,2,3-thiadiazol-5-yl
122 2,3-difluorophenyl
123 2,4-difluorophenyl
124 2-fiuoro-5 -trifluoromethylphenyl
125 2-chloro-4-fiuorophenyl Table J:
Figure imgf000256_0001
Comp. Q
No.
Jl 2-chloro-4-cyanophenyl
J2 2,6-difluoro-4-cyanophenyl
J3 2,4,6-trifluorophenyl
J4 2-methyl-4-cyanophenyl
J5 2-fluorophenyl
J6 2-methylphenyl
J7 2-chlorophenyl
J8 4-cyanophenyl
J9 4-nitrophenyl
J10 4-methylphenyl
Jl 1 4-fluoro-2-methylphenyl
J12 5 -chloro-2-fluorophenyl
J13 2-chloro-4-nitrophenyl
J14 furan-2-yl
J15 4-trifluoromethoxyphenyl
J16 4-fluoro-3 -trifluoromethylphenyl
J17 4-trifiuoromethylphenyl
J18 2-trifiuoromethoxyphenyl
J19 2-methoxyphenyl J20 phenyl
J21 4-fluorophenyl
J22 2-trifluoromethylphenyl
J23 4-methyl- 1 ,2,3-thiadiazol-5-yl
J24 2,3-difluorophenyl
J25 2,4-difluorophenyl
J26 2-fluoro-5 -trifluoromethylphenyl
J27 2-chloro-4-fiuorophenyl
Table K:
Figure imgf000257_0001
Comp. Q
No.
Kl 2,4,6-trifiuorophenyl
K2 4-nitrophenyl
K3 2-chloro-4-cyanohenyl
K4 2-methyl -4-cyanophenyl Table L:
Figure imgf000258_0001
Comp. Q
No.
LI 2-fluorophenyl
L2 2-methylphenyl
L3 2-chlorophenyl
L4 4-cyanophenyl
L5 4-nitrophenyl
L6 4-methylphenyl
L7 4-fluoro-2-methylphenyl
L8 5 -chloro-2-fluorophenyl
L9 2-chloro-4-nitrophenyl
L10 furan-2-yl
Ll l 4-trifluoromethoxyphenyl
L12 4-fluoro-3 -trifluoromethylphenyl
L13 4-trifiuoromethylphenyl
L14 2-trifiuoromethoxyphenyl
L15 2-methoxyphenyl
L16 phenyl
L17 4-fiuorophenyl
L18 2-trifiuoromethylphenyl
L19 2-chloro-4-fiuorophenyl L20 4-methyl- 1 ,2,3-thiadiazol-5-yl
L21 2,3-difluorophenyl
L22 2,4-difluorophenyl
L23 2-fluoro-5 -trifluoromethylphenyl
Table M:
Figure imgf000259_0001
Figure imgf000259_0003
In an embodiment of the embodiment (K) the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000259_0002
wherein
X1 is N02, NH2, a group of formula (II) or a group of formula (III)
Figure imgf000260_0001
(I I) (I N)
G1 and G2 are each independently oxygen or sulfur;
Q1 is aryl or heterocyclyl, each optionally substituted by one to five R3 substituents, which may be the same or different;
R1 is hydrogen, Ci-C8alkyl, Ci-C8alkylcarbonyl, or Ci-C8alkoxycarbonyl;
R2 is hydrogen, Ci-C8alkyl, Ci-C8alkylcarbonyl, or Ci-C8alkoxycarbonyl;
R3 is halogen, cyano, nitro, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, or
Ci-C4haloalkoxy;
Q2 is a group of formula IV)
Figure imgf000260_0002
Y1 and Y5 are each independently selected from halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, Ci-C4alkoxy-Ci-C4alkyl, Ci-C3alkylthio, Ci-Cshaloalkylthio, Ci-C3alkylsulfinyl, Ci-Cshaloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y3 is selected from C2-C6perfiuoroalkyl, C2-C6perfluorocycloalkyl, hydroxy- C2-C6perfluoroalkyl, Ci-C4alkylcarbonyloxy-C2-C6perfluoroalkyl,
Ci-C4haloalkylcarbonyloxy-C2-C6perfluoroalkyl, Ci-C6perfluoroalkylthio,
C i -C6perfluoroalkylsulfinyl, C i -Ceperfluoroalkylsulfonyl, arylcarbonyloxy- C2-C6perfluoroalkyl, and arylcarbonyloxy-C2-C6perfluoroalkyl in which the aryl group may be substituted by one to five R4 groups, which may be the same or different;
Y2 and Y4 are each independently selected from hydrogen, halogen and Ci-C4alkyl; and
R4 is halogen, cyano, nitro, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy or
Ci-C4haloalkoxy; or an agrochemically acceptable salt or N-oxides thereof.
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment of the embodiment (K) the preferred values of X1, G1, G2, Q1, R1, R2, R3, Q2, Y1, Y2, Y3, Y4, Y5 and R4 are, in any combination, as set out below.
In a first preferred aspect of the invention, X1 is N02.
In a second preferred aspect of the invention, X1 is NH2.
In a third preferred aspect of the invention, X1 is a group of formula (II)
In a fourth preferred aspect of the invention, X1 is a group of formula (III).
Preferably, G1 is oxygen.
Preferably, G2 is oxygen.
Preferably, Q1 is aryl or heteroaryl; each optionally substituted by one to five R3 substituents, which may be the same or different.
More preferably, Q1 is selected from phenyl, biphenyl and a five to six-membered monocyclic heteroaryl group containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; each optionally substituted by one to five R3 substituents, which may be the same or different.
Yet more preferably, Q1 is selected from phenyl, biphenyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, benzothiadiazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl; each optionally substituted by one to five R3, and more preferably by one to three R3 substituents, which may be the same or different.
Even more preferably, Q1 is selected from phenyl, biphenyl, furanyl, pyridyl, thienyl, thiadiazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl and pyrimidinyl; each optionally substituted by one to three R3 substituents, which may be the same or different.
Even more preferably, Q1 is phenyl, optionally substituted by one to three R3 substituents, which may be the same or different.
Preferably, R3 is selected from cyano, nitro, fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, methoxy and trifluoromethoxy. Most preferably, R3 is selected cyano, nitro, chloro, fluoro and methyl.
Most preferably, Q1 is selected from 4-cyanophenyl, 4-fluorophenyl, 2-methyl-3- nitrophenyl and 2-chloro-4-fluorophenyl.
Preferably, R1 is hydrogen, methyl or ethyl and most preferably, hydrogen.
Preferably, R2 is hydrogen.
Preferably, Y1 is halogen, cyano, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl or Ci-C3alkylthio. More preferably, Y1 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl. Most preferably, Y1 is chloro, bromo, methyl, ethyl, or cyano.
Preferably, Y2 is hydrogen, chloro, fluoro or methyl. More preferably, Y2 is hydrogen or fluoro. Most preferably, Y2 is hydrogen.
Preferably, Y3 is C2-C6perfluoroalkyl. More preferably, Y3 is heptafluoropropyl or nonafluorobutyl. Yet more preferably, Y3 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
Preferably, Y4 is hydrogen, chloro, fluoro or methyl. More preferably, Y4 is hydrogen or fluoro. Most preferably, Y4 is hydrogen.
Preferably, Y5 is halogen, cyano, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl or Ci-C3alkylthio. More preferably, Y5 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl. Most preferably, Y5 is chloro, bromo, methyl, ethyl, or cyano.
Preferably, R4 is chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, or trifluoromethoxy.
Preferably, Q2 is 2,6-dimethyl-4-(heptafluoroprop-2-yl)phenyl, 2,6-diethyl-4- (heptafluoroprop-2-yl)phenyl, 2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl, 2,6-dibromo- 4-(nonafluorobut-2-yl)phenyl, 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl, or
2,6-dichloro-4-(nonafluoro-but-2-yl)phenyl.
Most preferably, Q2 is 2,6-dimethyl-4-(heptafluoroprop-2-yl)phenyl, 2,6-diethyl-4- (heptafluoroprop-2-yl)phenyl, 2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl, 2,6-dibromo- 4-(nonafluorobut-2-yl)phenyl.
In a preferred embodiment of the embodiment (K) of the first aspect of the invention,
X1 is N02.
G2 is oxygen;
R2 is hydrogen; Y1 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl;
Y2 and Y4 are both hydrogen;
Y3 is heptafluoroprop-l-yl, heptafiuoroprop-2-yl, nonafluorobut-2-yl or
undecafluorocyclohexyl; and
Y5 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl .
In a more preferred embodiment of the embodiment (K) of the first aspect of the invention,
X1 is N02.
G2 is oxygen;
R2 is hydrogen; and
Q2 is 2,6-dimethyl-4-(heptafluoroprop-2-yl)phenyl, 2,6-diethyl-4-(heptafluoroprop-2- yl)phenyl, 2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl, 2,6-dibromo-4-(nonafluorobut-2- yl)phenyl, 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl, or 2,6-dichloro-4-(nonafluoro- but-2-yl)phenyl.
In a preferred embodiment of the embodiment (K) of the second aspect of the invention,
X1 is NH2;
G2 is oxygen;
R2 is hydrogen;
Y1 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl;
Y2 and Y4 are both hydrogen;
Y3 is heptafluoroprop-l-yl, heptafluoroprop-2-yl, nonafluorobut-2-yl or
undecafluorocyclohexyl; and
Y5 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl .
In a more preferred embodiment of the embodiment (K) of the second aspect of the invention,
X1 is NH2;
G2 is oxygen;
R1 and R2 are both hydrogen; and Q2 is 2,6-dimethyl-4-(heptafiuoroprop-2-yl)phenyl, 2,6-diethyl-4-(heptafiuoroprop-2- yl)phenyl, 2-ethyl-6-methyl-4-(nonafiuorobut-2-yl)phenyl, 2,6-dibromo-4-(nonafluorobut-2- yl)phenyl, 2-bromo-6-chloro-4-(nonafiuoro-but-2-yl)phenyl, or 2,6-dichloro-4-(nonafluoro- but-2-yl)phenyl.
In a preferred embodiment of the embodiment (K) of the third aspect of the invention,
X1 is a group of formula (II)
G2 is oxygen;
R2 is hydrogen;
Y1 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl;
Y2 and Y4 are both hydrogen;
Y3 is heptafluoroprop-l-yl, heptafluoroprop-2-yl, nonafluorobut-2-yl or
undecafluorocyclohexyl; and
Y5 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl .
In a more preferred embodiment of the embodiment (K) of the third aspect of the invention,
X1 is a group of formula (II)
X1 is NH2;
G2 is oxygen;
R1 and R2 are both hydrogen; and
Q2 is 2,6-dimethyl-4-(heptafluoroprop-2-yl)phenyl, 2,6-diethyl-4-(heptafluoroprop-2- yl)phenyl, 2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl, 2,6-dibromo-4-(nonafluorobut-2- yl)phenyl, 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl, or 2,6-dichloro-4-(nonafluoro- but-2-yl)phenyl.
In a preferred embodiment of the embodiment (K) of the fourth aspect of the invention,
X1 is a group of formula (III);
G1 and G2 are both oxygen;
R1 and R2 are both hydrogen;
Q1 is phenyl, optionally substituted by one to three R3 substituents, which may be the same or different; R3 is selected from cyano, nitro, fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, methoxy and trifluoromethoxy.
Y1 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or
methoxymethyl;
Y2 and Y4 are both hydrogen;
Y3 is heptafluoroprop-l-yl, heptafluoroprop-2-yl, nonafluorobut-2-yl or
undecafluorocyclohexyl; and
Y5 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or
methoxymethyl .
In a more preferred embodiment of the embodiment (K) of the fourth aspect of the invention,
X1 is a group of formula (III);
G1 and G2 are both oxygen;
R1 and R2 are both hydrogen;
Q1 is 4-cyanophenyl, 4-fluorophenyl, 2-methyl-3-nitrophenyl or 2-chloro-4- fluorophenyl.
Q2 is 2,6-dimethyl-4-(heptafluoroprop-2-yl)phenyl, 2,6-diethyl-4-(heptafluoroprop-2- yl)phenyl, 2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl, 2,6-dibromo-4-(nonafluorobut-2- yl)phenyl, 2-bromo-6-chloro-4-(nonafluoro-but-2-yl)phenyl, or 2,6-dichloro-4-(nonafluoro- but-2-yl)phenyl.
Most preferred compounds of formula (I) are selected from
N-[2,6-dibromo-4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -trifluoromethylpropyl)phenyl] -3-nitro-4-( 1 ,2,4- triazol- 1 -yl)benzamide;
3-amino-N-[2,6-dibromo-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-phenyl]-4- ( 1 ,2,4-triazol- 1 -yl)benzamide;
3-(4-cyanobenzoylamino)-N-[2,6-dibromo-4-(l, 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl] -4-( 1 ,2,4-triazol- 1 -yl)benzamide; 3-(2-methyl-3-nitrobenzoylamino)-N-[2-ethyl-4-(l , 2,2,3, 3,3-hexafluoro-l - trifluoromethylpropyl)-6-methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide;
3-(2-chloro-4-fluorobenzoylamino)-N-[2-ethyl-4-( 1 ,2,2,3 ,3 ,3 -hexafluoro- 1 - trifluoromethylpropyl)-6-methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide;
3-(4-cyanobenzoylamino)-N-[2-ethyl-4-(l ,2,2,3,3,3-hexafluoro-l-trifluoromethyl-propyl)-6- methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide;
3-(2-chloro-4-fluorobenzoylamino)-N-[2,6-dibromo-4-(l , 2,2,3, 3, 3 -hexafluoro- 1- trifluoromethylpropyl)phenyl] -4-( 1 ,2,4-triazol- 1 -yl)benzamide;
3-(2-methyl-3-nitrobenzoylamino)-N-[2,6-dibromo-4-(l , 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl] -4-( 1 ,2,4-triazol- 1 -yl)benzamide;
3-(4-fluorobenzoylamino)-N-[2,6-diethyl-4-(l ,2,2,2-tetrafluoro-l- trifluoromethylethyl)phenyl] -4-( 1 ,2,4-triazol- 1 -yl)benzamide;
3-(4-fluorobenzoylamino)-N-[2,6-dimethyl-4-(l ,2,2,2-tetrafluoro-l-trifluoromethyl- ethyl)phenyl]-4-(l ,2,4-triazol-l-yl)benzamide;
3-(4-fluorobenzoylamino)-N-[2-ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethyl-propyl)-6- methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide; and
3-(4-fluorobenzoylamino)-N-[2,6-dibromo-4-( 1 ,2,2,3 ,3 ,3 -hexafluoro- 1 - trifluoromethylpropyl)phenyl] -4-( 1 ,2,4-triazol- 1 -yl)benzamide.
The following compounds illustrate the compounds of the invention according to the embodiment (K)
N-[2,6-dibromo-4-( 1 ,2,2,3 ,3 ,3 -hexafluoro- 1 -trifluoromethylpropyl)phenyl] -3-nitro-4-( 1 ,2,4- triazol- l-yl)benzamide (Compound No. A4 of Table A)
N-[2-Ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -trifluoromethylpropyl)-6-methylphenyl]-3-nitro-4- (l ,2,4-triazol-l-yl)benzamide (Compound No. A3 of Table A).
N-[2,6-Diethyl-4-(l ,2,2,2-tetrafluoro-l-trifluoromethylethyl)phenyl]-3-nitro-4-(l ,2,4-triazol- l-yl)benzamide (Compound No. A2 of Table A), using dichloromethane as solvent.
N-[2,6-Dimethyl-4-(l ,2,2,2-tetrafluoro-l-trifluoromethylethyl)phenyl]-3-nitro-4-(l ,2,4- triazol-l-yl)benzamide (Compound No. Al of Table A), using dichloromethane as solvent. 3-amino-N-[2,6-dibromo-4-(l , 2,2,3, 3, 3 -hexafluoro- l-trifluoromethylpropyl)-phenyl] -4- (l ,2,4-triazol-l-yl)benzamide (Compound No. B4 of Table B) 3-Amino-N-[2-ethyl-4-(l , 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-6-methyl-phenyl]-4- (l ,2,4-triazol-l-yl)benzamide (Compound No. B3 of Table B).
3-amino-N-[2,6-diethyl-4-(l ,2,2,2-tetrafluoro-l -trifluoromethylethyl)phenyl]-4-(l ,2,4- triazol-l-yl)benzamide (Compound No. B2 of Table B)
3-Amino-N-[2,6-dimethyl-4-(l ,2,2,2-tetrafluoro-l -trifluoromethylethyl)phenyl]-4-(l ,2,4- triazol-l-yl)benzamide (Compound No. B l of Table B).
3-(4-cyanobenzoylamino)-N-[2,6-dibromo-4-(l , 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D8 of Table D)
3-(2-Methyl-3-nitrobenzoylamino)-N-[2-ethyl-4-( 1 ,2,2,3,3,3 -hexafluoro- 1 - trifluoromethylpropyl)-6-methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D3 of Table D).
3-(2-Chloro-4-fluorobenzoylamino)-N-[2-ethyl-4-(l , 2,2,3, 3,3-hexafluoro-l - trifluoromethylpropyl)-6-methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D4 of Table D).
3-(4-Cyanobenzoylamino)-N-[2-ethyl-4-(l , 2,2,3, 3,3-hexafluoro-l-trifluoromethyl-propyl)-6- methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D5 of Table D).
3-(2-Chloro-4-fluorobenzoylamino)-N-[2,6-dibromo-4-(l , 2,2,3, 3, 3 -hexafluoro- 1- trifluoromethylpropyl)phenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D9 of Table D).
3-(2-Methyl-3-nitrobenzoylamino)-N-[2,6-dibromo-4-(l , 2,2,3, 3, 3 -hexafluoro- 1 - trifluoromethylpropyl)phenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D10 of Table D).
3-(4-fluorobenzoylamino)-N-[2,6-diethyl-4-(l ,2,2,2-tetrafluoro-l- trifluoromethylethyl)phenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D2 of Table D)
3-(4-Fluorobenzoylamino)-N-[2,6-dimethyl-4-(l ,2,2,2-tetrafluoro-l-trifluoromethyl- ethyl)phenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. Dl of Table D).
3-(4-Fluorobenzoylamino)-N-[2-ethyl-4-(l ,2,2,3,3,3-hexafluoro-l-trifluoromethyl-propyl)-6- methylphenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D6 of Table D).
3-(4-Fluorobenzoylamino)-N-[2,6-dibromo-4-(l , 2,2,3, 3, 3 -hexafluoro- 1 - trifluoromethylpropyl)phenyl]-4-(l ,2,4-triazol-l-yl)benzamide (Compound No. D7 of Table D), using tetrahydrofuran as solvent. Or a compozuun according to the following Tables A to D:
Table A:
Compounds of formula (la) wherein G2 is oxygen and R2 is hydrogen.
Figure imgf000268_0001
R" " Q
Figure imgf000268_0003
Table B:
Compounds of formula (lb) where G2 is oxygen and R2 is hydrogen.
Figure imgf000268_0002
Comp.
Q2
No.
Bl 2,6-dimethyl-4-(heptafluoroprop-2-yl)phenyl
B2 2,6-diethyl-4-(heptafluoroprop-2-yl)phenyl
B3 2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl
B4 2,6-dibromo-4-(nonafluorobut-2-yl)phenyl Table C:
Compounds of formula (Ic) where G2 is oxygen, R1 is ethyl, R2 is hydrogen and Q2 is 2,6-diethyl-4-(heptafluoroprop-2-yl)phenyl. (only one compound (CI))
Figure imgf000269_0001
Table D:
Compounds of formula (Id) where G1 and G2 are oxygen and R1 and R2 are hydrogen.
Figure imgf000269_0002
Comp.
Q1 Q2
No.
2,6-dimethyl-4-(heptafluoroprop-
Dl 4-fluorophenyl
2-yl)phenyl
2,6-diethyl-4-(heptafluoroprop-2-
D2 4-fluorophenyl
yl)phenyl
2-methyl-3- 2-ethyl-6-methyl-4-
D3
nitrophenyl (nonafluorobut-2 -yl)pheny 1
2-chloro-4- 2-ethyl-6-methyl-4-
D4
fluorophenyl (nonafluorobut-2 -yl)pheny 1 Comp.
Q1 Q2
No.
2-ethyl-6-methyl-4-
D5 4-cyanophenyl
(nonafluorobut-2 -yl)pheny 1
2-ethyl-6-methyl-4-
D6 4-fluorophenyl
(nonafluorobut-2 -yl)pheny 1
2,6-dibromo-4-(nonafluorobut-2-
D7 4-fluorophenyl
yl)phenyl
2,6-dibromo-4-(nonafluorobut-2-
D8 4-cyanophenyl
yl)phenyl
2-chloro-4- 2,6-dibromo-4-(nonafluorobut-2-
D9
fluorophenyl yl)phenyl
2-methyl-3- 2,6-dibromo-4-(nonafluorobut-2-
D10
nitrophenyl yl)phenyl
In an embodiment (L), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000270_0001
R1 is hydrogen, Ci-Csalkyl, Ci-Csalkylcarbonyl, or Ci-Csalkoxycarbonyl;
R2 is hydrogen, Ci-C8alkyl, Ci-C8alkylcarbonyl, or Ci-C8alkoxycarbonyl;
each R3 is independently halogen;
n is 0, 1 , 2 or 3; Q2 is a group of formula
Figure imgf000271_0001
Y1 and Y5 are each independently selected from halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, Ci-C4alkoxy-Ci-C4alkyl, Ci-C3alkythio, Ci-Cshaloalkylthio, Ci-C3alkylsulfmyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl and Ci-C3haloalkylsulfonyl;
Y3 is selected from C2-C6perfiuoroalkyl, C2-C6perfiuorocycloalkyl, hydroxy- C2-C6perfluoroalkyl, Ci-C4alkylcarbonyloxy-C2-C6perfluoroalkyl,
Ci-C4haloalkylcarbonyloxy-C2-C6perfluoroalkyl, Ci-C6perfluoroalkylthio,
Ci-C6perfluoroalkylsulfinyl, Ci-C6perfluoroalkylsulfonyl, arylcarbonyloxy-
C2-C6perfluoroalkyl and arylcarbonyloxy-C2-C6perfluoroalkyl in which the aryl group may be substituted by one to five R4 groups, which may be the same or different;
Y2 and Y4 are each independently selected from hydrogen, halogen and Ci-C4alkyl; and
R4 is halogen, cyano, nitro, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy or Ci-
C4haloalkoxy;
or an agrochemically acceptable salt or N-oxides thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodiment (L) the preferred values of R1, R2, R3, n, Q2, Y1, Y2, Y3, Y4, Y5 and R4 are, in any combination, as set out below.
Preferably, R1 is hydrogen.
Preferably, R2 is hydrogen.
Preferably, R3 is fluoro.
In one preferred aspect, n is 0.
In another preferred aspect, n is 1. When n is 1 , the R3 group is preferably substituted in the 2-position of the phenyl ring. Preferably, Y1 is halogen, cyano, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl or Ci-C3alkylthio. More preferably, Y1 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl. Most preferably, Y1 is chloro, bromo, methyl, ethyl, or cyano.
Preferably, Y2 is hydrogen, chloro, fluoro or methyl. More preferably, Y2 is hydrogen or fluoro. Most preferably, Y2 is hydrogen.
Preferably, Y3 is C2-C6perfluoroalkyl, C2-C6perfiuorocycloalkyl, hydroxy- C2-C6perfluoroalkyl, arylcarbonyloxy-C2-C6perfluoroalkyl, or arylcarbonyloxy- C2-C6perfluoroalkyl in which the aryl group may be substituted by one to five R4 groups, which may be the same or different. More preferably, Y3 is heptafluoropropyl,
nonafluorobutyl, undecafluorocyclohexyl, heptafluoropropylthio, heptafluoropropylsulfinyl, or heptafluoropropylsulfonyl. Yet more preferably, Y3 is heptafluoroprop-l-yl,
heptafluoroprop-2-yl, nonafluorobut-2-yl or undecafluorocyclohexyl. Most preferably, Y3 is heptafluoroprop-2-yl, nonafluorobut-2-yl or undecafluorocyclohexyl.
Preferably, Y4 is hydrogen, chloro, fluoro or methyl. More preferably, Y4 is hydrogen or fluoro. Most preferably, Y4 is hydrogen.
Preferably, Y5 is halogen, cyano, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl or Ci-C3alkylthio. More preferably, Y5 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl. Most preferably, Y5 is chloro, bromo, methyl, ethyl, or cyano.
Preferably, R4 is chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, or trifluoromethoxy.
Most preferably, Q2 is selected from
2-bromo-6-chloro-4-(hexafluoro-2-benzoyloxyprop-2-yl)phenyl,
2-bromo-6-chloro-4-(hexafluoro-2-hydroxyprop-2-yl)phenyl,
2-bromo-6-chloro-4-(nonafluorobut-2-yl)phenyl,
2-bromo-6-ethyl-4-(nonafluorobut-2-yl)phenyl,
2-chloro-6-cyano-4-(nonafluorobut-2-yl)phenyl,
2-chloro-6-methylthio-4-(nonafluorobut-2-yl)phenyl,
2,6-dibromo-4-(heptafluoroprop-2-yl)phenyl,
2,6-dibromo-4-(nonafluorobut-2-yl)phenyl,
2,6-dichloro-3-fluoro-4-(heptafluoroprop-2-yl)phenyl,
2,6-dichloro-4-(nonafluorobut-2-yl)phenyl, 2,6-dimethyl-4-(nonafluorobut-2-yl)phenyl,
2,6-dimethyl-4-(undecafluorocyclohexyl)phenyl,
2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl,
2-ethyl-6-methyl-4-(octafluoro-2-hydroxybut-2-yl)phenyl,
2-methoxymethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl, and
2-methoxy-6-methyl-4-(nonafluorobut-2-yl)phenyl.
In a preferred embodiment of the embodiment (L) of the invention,
R1 and R2 are both hydrogen;
n is 0 or 1 ;
Y1 is halogen, cyano, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl or Ci-C3alkylthio;
Y2 and Y4 are both hydrogen;
Y3 is heptafluoropropyl, nonafluorobutyl, undecafluorocyclohexyl, heptafluoropropylthio, heptafluoropropylsulfinyl, or heptafluoropropylsulfonyl; and
Y5 is halogen, cyano, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl or Ci-C3alkylthio.
In a more preferred embodiment of the embodiment (L) of the invention, R1 and R2 are both hydrogen;
n is 0 or 1 ;
Y1 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl;
Y2 and Y4 are both hydrogen;
Y3 is heptafluoroprop-l-yl, heptafluoroprop-2-yl, nonafluorobut-2-yl or undecafluorocyclohexyl; and
Y5 is fluoro, chloro, bromo, cyano, methyl, ethyl, methoxy, methylthio, or methoxymethyl .
In a yet more preferred embodiment of the embodiment (L) of the invention, R1 and R2 are both hydrogen;
n is 0 or 1 ;
R3 is fluoro; Y1 is chloro, bromo, methyl, ethyl, or cyano;
Y2 and Y4 are both hydrogen;
Y3 is heptafluoroprop-2-yl, nonafluorobut-2-yl or undecafluorocyclohexyl; and Y5 is chloro, bromo, methyl, ethyl, or cyano.
In a first preferred aspect of the invention,
R1 and R2 are both hydrogen;
n is 1;
R3 is 2-fluoro; and
Q2 is selected from
2-bromo-6-chloro-4-(hexafluoro-2-benzoyloxyprop-2-yl)phenyl,
2-bromo-6-chloro-4-(hexafluoro-2-hydroxyprop-2-yl)phenyl,
2-bromo-6-chloro-4-(nonafluorobut-2-yl)phenyl,
2-bromo-6-ethyl-4-(nonafluorobut-2-yl)phenyl,
2-chloro-6-cyano-4-(nonafluorobut-2-yl)phenyl,
2-chloro-6-methylthio-4-(nonafluorobut-2-yl)phenyl,
2,6-dibromo-4-(heptafluoroprop-2-yl)phenyl,
2,6-dibromo-4-(nonafluorobut-2-yl)phenyl,
2,6-dichloro-3-fluoro-4-(heptafluoroprop-2-yl)phenyl,
2,6-dichloro-4-(nonafluorobut-2-yl)phenyl,
2,6-dimethyl-4-(nonafluorobut-2-yl)phenyl,
2,6-dimethyl-4-(undecafluorocyclohexyl)phenyl,
2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl,
2-ethyl-6-methyl-4-(octafluoro-2-hydroxybut-2-yl)phenyl,
2-methoxymethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl, and
2-methoxy-6-methyl-4-(nonafluorobut-2-yl)phenyl.
In a second preferred aspect of the invention,
R1 and R2 are both hydrogen;
n is 0; and
Q2 is selected from
2-bromo-6-chloro-4-(hexafluoro-2-benzoyloxyprop-2-yl)phenyl, 2-bromo-6-chloro-4-(hexafluoro-2-hydroxyprop-2-yl)phenyl, 2-bromo-6-chloro-4-(nonafluorobut-2-yl)phenyl,
2-bromo-6-ethyl-4-(nonafluorobut-2-yl)phenyl,
2-chloro-6-cyano-4-(nonafluorobut-2-yl)phenyl,
2-chloro-6-methylthio-4-(nonafiuorobut-2-yl)phenyl,
2,6-dibromo-4-(heptafiuoroprop-2-yl)phenyl,
2,6-dibromo-4-(nonafluorobut-2-yl)phenyl,
2,6-dichloro-3-fiuoro-4-(heptafluoroprop-2-yl)phenyl,
2,6-dichloro-4-(nonafiuorobut-2-yl)phenyl,
2,6-dimethyl-4-(nonafluorobut-2-yl)phenyl,
2,6-dimethyl-4-(undecafiuorocyclohexyl)phenyl,
2-ethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl,
2-ethyl-6-methyl-4-(octafiuoro-2-hydroxybut-2-yl)phenyl,
2-methoxymethyl-6-methyl-4-(nonafluorobut-2-yl)phenyl.
2-methoxy-6-methyl-4-(nonafluorobut-2-yl)phenyl.
Most preferred compounds of formula (I) are selected from
4-cyano-3-(4'-cyano-2'-methyl-benzoylamino)-N-[2,6-dibromo-4-(l , 2,2,3, 3 ,3- hexafluoro- 1 -trif uoromethyl-propyl)-phenyl]-benzamide;
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dichloro-4-(l , 2,2,3, 3 ,3- hexafluoro- 1 -trif uoromethylpropyl)phenyl]-2-fiuorobenzamide;
N-[2-chloro-6-cyano-4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -trifiuoromethylpropyl)phenyl] -4- cyano-3-(4'-cyano-2'-methylbenzoylamino)benzamide;
N-[2-bromo-6-chloro-4-[l ,1 , 1 ,3,3,3-hexafiuoropropan-2-ol)phenyl]-4-cyano-3-(4'- cyano-2'-methylbenzoylamino)benzamide;
N-[2-bromo-6-chloro-4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -trifiuoromethylpropyl)phenyl] -4- cyano-3-(4'-cyano-2'-methylbenzoylamino)benzamide;
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dichloro-4-(l , 2,2,3, 3 ,3- hexafluoro- 1 -trif uoromethylpropyl)phenyl]benzamide;
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dichloro-4-(l ,2,2,2-tetrafluoro- 1 -trifiuoromethylethyl)phenyl]benzamide; and
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2-bromo-6-chloro-4-(l , 2,2,2- tetrafiuoro- 1 -trifiuoromethylethyl)phenyl]benzamide. The following compounds illustrate the compounds of the invention according to the embodiment (L)
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dibromo-4-(l, 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]benzamide (Compound No. A4 of Table A)
4-cyano-3 -(4'-cyano-2'-methylbenzoylamino)-N-[2-ethyl-6-methyl-4-( 1 ,2,2,3,3,3 -hexa- fluoro-l-trifluoromethylpropyl)phenyl]benzamide (Compound No. Al of Table A) was made from 3-amino-4-cyano-N-[2-ethyl-6-methyl-4-(l, 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]benzamide (made as in WO 2008/074427).
N-[2-bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-phenyl]-4-cyano-3-
(4'-cyano-2'-methylbenzoylamino)benzamide (Compound No. A2 of Table A) was made from 3-amino-N-[2-bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]-4-cyanobenzamide (Example 1.5).
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dibromo-4-(l,2,2,2-tetrafluoro-l- trifluoromethylethyl)phenyl]benzamide (Compound No. A3 of Table A) was made from 3- amino-4-cyano-N-[2,6-dibromo-4-( 1 ,2,2,3 ,3 ,3-tetrafluoro- 1 -trifluoromethyl- ethyl)phenyl]benzamide (prepared as described in WO 2008/074427).
N-[2-bromo-6-ethyl-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-phenyl]-4-cyano-3-
(4'-cyano-2'-methylbenzoylamino)benzamide (Compound No. A5 of Table A) was made from 3-amino-N-[2-bromo-6-ethyl-4-(l,2,2,3,3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]-4-cyanobenzamide (prepared as described in
WO 2008/074427).
N-[2-bromo-6-chloro-4-(l, 2,2,3, 3,3-hexafluoro-l-trifluoromethylpropyl)-phenyl]-4-cyano-3- (4'-cyano-2'-methylbenzoylamino)-2-fluorobenzamide (Compound No. A6 of Table A) was made from 3-amino-N-[2-bromo-6-chloro-4-(l,2,2,3,3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]-4-cyano-2-fluorobenzamide (Example 1.7).
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dichloro-4-(l, 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]benzamide (Compound No. A8 of Table A) was made from 3- amino-4-cyano-N-[2,6-dichloro-4-(l, 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]benzamide (Example 1.5).
4-cyano-3-(4'-cyano-2'-methyl-benzoylamino)-N-[4-(l, 2,2,3, 3,3-hexafluoro-l - trifluoromethylpropyl)-2-methoxymethyl-6-methylphenyl]benzamide (Compound No. A9 of Table A) was made from 3-amino-4-cyano-N-[4-(l,2,2,3,3,3-hexafluoro-l- trifluoromethylpropyl)-2-methoxymethyl-6-methylphenyl]benzamide (prepared as described in WO 2008/074427).
N-[2-chloro-4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -trifluoromethylpropyl)-6-methylthiophenyl]-4- cyano-3-(4'-cyano-2'-methylbenzoylamino)benzamide (Compound No. A10 of Table A) was made from 3-amino-N-[2-chloro-4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -trifluoromethylpropyl)-6- methylthiophenyl]-4-cyanobenzamide (Example 1.6).
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2-methoxy-6-methyl-4-(l , 2,2,3, 3,3- hexafluoro-l-trifluoromethylpropyl)phenyl]benzamide (Compound No. Al l of Table A) was made from 3-amino-4-cyano-N-[2-methoxy-6-methyl-4-(l , 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]benzamide (Example 1.5).
benzoic acid 1 - {3-bromo-5-chloro-4-[4-cyano-3-(4-cyano-2-methyl- benzoylamino)benzoylamino]phenyl} -2,2,2-trifluoro- 1 -trifluoromethylethyl ester
(Compound No. A12 of Table A) was made from benzoic acid l-[4-(3-amino-4-cyano- benzoylamino)-3-bromo-5-chlorophenyl]-2,2,2-trifluoro-l -trifluoromethylethyl ester (Example 1.5)
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dichloro-3-fluoro-4-(l , 2,2,2- tetrafluoro-l-trifluoromethylethyl)phenyl]benzamide (Compound No. A14 of Table A) was made from 3-amino-4-cyano-N-[2,6-dichloro-3-fluoro-4-(l ,2,2,2-tetrafluoro-l- trifluoromethylethyl)phenyl]benzamide (Example 1.5).
4-cyano-3-(4'-cyano-2'-methyl-benzoylamino)-N-[2-ethyl-6-methyl-4-(2,2,3,3,3-pentafluoro- 1 -hydroxy- l-trifluoromethylpropyl)phenyl]benzamide (Compound No. A15 of Table A) was made from 3-amino-4-cyano-N-[2-ethyl-6-methyl-4-(2,2,3 ,3 ,3 -pentafluoro- 1 -hydroxy- 1 - trifluoromethylpropyl)phenyl]benzamide (Example 1.5).
4-cyano-3-(4'-cyano-2'-methyl-benzoylamino)-N-[2,6-dimethyl-4-( 1 ,2,2,3 ,3 ,3 -hexafluoro- 1 - trifluoromethylpropyl)phenyl]benzamide (Compound No. A16 of Table A) was made from
3- amino-4-cyano-N-[2,6-dimethyl-4-(l , 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]benzamide (Example 1.5).
4- cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dimethyl-4-
(undecafluorocyclohexyl)phenyl]benzamide (Compound No. A17 of Table A) was made from 3-amino-4-cyano-N-[2,6-dimethyl-4-(undecafluorocyclohexyl)phenyl]benzamide (Example 1.5).
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dichloro-4-(l ,2,2,2-tetrafluoro-l- trifluoromethylethyl)phenyl]benzamide (Compound No. A19 of Table A) was made from 3- amino-4-cyano-N-[2,6-dichloro-4-( 1 ,2,2,2-tetrafluoro- 1 -trifluoromethylethyl)- phenyljbenzamide (Example 1.5).
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2-bromo-6-chloro-4-(l ,2,2,2-tetrafluoro-l- trifluoromethylethyl)phenyl]benzamide (Compound No. A20 of Table A) was made from 3- amino-N-[2-bromo-6-chloro-4-(l ,2,2,2-tetrafluoro-l-trifluoromethyl-ethyl)phenyl]-4- cyanobenzamide (Example 1.5).
4-cyano-3-(4'-cyano-2'-methylbenzoylamino)-N-[2,6-dichloro-4-(l , 2,2,3, 3,3-hexafluoro-l- trifluoromethylpropyl)phenyl]-2-fluorobenzamide
(Compound No. A18 of Table A)
N- [2-chloro-6-cyano-4-( 1 ,2,2,3 ,3 ,3 -hexafluoro- 1 -trifluoromethylpropyl)-phenyl] -4-cyano-3 - (4'-cyano-2'-methylbenzoylamino)benzamide
(Compound No. A7 of Table A)
N-[2-bromo-6-chloro-4-[l ,l , l ,3,3,3-hexafluoropropan-2-ol)phenyl]-4-cyano-3-(4'-cyano-2'- methylbenzoylamino)benzamide (Compound No. A13 of Table A)
Or a compound as described in the Table A:
Table A:
Figure imgf000278_0001
Comp.
R3 n
No.
Al - 0
A2 - 0
A3 - 0
A4 - 0
A5 - 0
A6 2-F 1
A7 - 0 Comp.
R3 n
No.
A8 - 0
A9 - 0
A10 - 0
Al l - 0
A12 - 0
A13 - 0
A14 - 0
A15 - 0
A16 - 0
A17 - 0
A18 2-F 1
A19 - 0
A20 - 0
In an embodiment of the embodiment (M), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000279_0001
A1, A2, A3 and A4 are each independently C-X or nitrogen, wherein each X may be same or different, and provided that no more than two of A1, A2, A3 and A4 are nitrogen;
X is hydrogen, halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl or Ci-C4alkoxy;
G1 and G2 are each independently oxygen or sulfur; Y1 and Y4 are each independently halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy-Ci-C4alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl,
Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl or Ci-C3haloalkylsulfonyl;
Y2 and Y3 are each independently hydrogen, halogen or Ci-C4alkyl;
Q1 is aryl or heterocyclyl, each optionally substituted by one to five R3 substituents, which may be the same or different;
Q2 is aryl or heterocyclyl, each optionally substituted by one to five R4 substituents, which may be the same or different;
R1 and R2 are each independently hydrogen, Ci-C4alkyl or Ci-C4alkylcarbonyl;
R3 is halogen, cyano, nitro, amino, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl,
C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C8cycloalkyl, C3-Cshalocycloalkyl, hydroxy, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio,
Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, N-Ci-C4alkylamino, N,N-di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxycarbonyl, Ci-C4alkylcarbonylamino, arylcarbonylamino or phenyl;
R4 is halogen, cyano, nitro, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl,
C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C8cycloalkyl, C3-Cshalocycloalkyl, hydroxy, Ci-C3alkoxy, Ci-C3haloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio,
Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, amino, Ci-C4alkylamino, N,N-di-(Ci-C4alkyl)amino, carboxyl (-COOH),
Ci-C4alkoxycarbonyl, Ci-C4alkylcarbonylamino, N-Ci-C4alkylaminocarbonyl,
N,N-di(Ci-C4alkyl)aminocarbonyl; and
R5 is Ci-C6perfluoroalkyl; or a salt or N-oxide thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans.
In the embodoiment (N) the preferred values of A1, A2, A3, A4, X, R1, R2, R5, G1, G2,
Figure imgf000280_0001
Υ2, Y3 and Y4 are, in any combination, as set out below.
Preferably, A1 is C-X.
Preferably, A2 is C-X.
Preferably, A3 is C-X.
Preferably, A4 is C-X. Preferably, X is hydrogen, halogen, cyano, methyl, trifiuoromethyl or methoxy. More preferably, X is hydrogen, fluoro, chloro, cyano, trifiuoromethyl or methoxy. Most preferably, X is hydrogen, fluoro, cyano or methoxy.
More preferably, A1, A2, A3 and A4 are C-X and each X is independently selected from hydrogen, halogen, cyano, methyl, trifiuoromethyl and methoxy. Most preferably, A1, A2, A3 and A4 are C-X and each X is independently selected from hydrogen, fluoro, cyano and methoxy.
More preferably, A1 is C-X1 and A2 is C-X2 and A3 is C-X3 and A4 is C-X4 and X1 and X4 are independently selected from hydrogen, halogen, cyano, methyl, trifiuoromethyl
2 3 1 1 2 2 and methoxy and and X and X are both H. Most preferably, A is C-X and A is C-X and A3 is C-X3 and A4 is C-X4 and X1 and X4 are independently selected from from hydrogen, fluoro, cyano and methox. and and X2 and X3 are both H even more preferably X1 and X4 are independently selected from from fluoro, cyano and methoxy. and and X2 and X3 are both H
Preferably, G1 is oxygen.
Preferably, G2 is oxygen.
More preferably, G1 is oxygen and G2 is oxygen.
Preferably, Y1 is bromo, chloro, cyano, methyl, ethyl, methoxymethyl,
trifiuoromethyl, trifluoromethylthio, trifluoromethylsulfmyl or trifluoromethylsulfonyl. More preferably, Y1 is halogen, cyano, methyl, ethyl, methoxymethyl or trifiuoromethyl. Even more preferably, Y1 is bromo, chloro or methyl. Most preferably, Y1 is chloro or methyl.
Preferably, Y2 is hydrogen, fluoro, chloro or methyl. Most preferably, Y2 is hydrogen.
Preferably, Y3 is hydrogen, fluoro, chloro or methyl. Most preferably, Y3 is hydrogen.
Preferably, Y4 is bromo, chloro, cyano, methyl, ethyl, methoxymethyl,
trifiuoromethyl, trifluoromethylthio, trifluoromethylsulfmyl or trifluoromethylsulfonyl. More preferably, Y4 is halogen, cyano, methyl, ethyl, methoxymethyl or trifiuoromethyl. Even more preferably, Y4 is bromo, chloro or methyl. Most preferably, Y4 is chloro or methyl.
Preferably, R1 is hydrogen, methyl, ethyl or acetyl. More preferably, R1 is hydrogen, methyl or ethyl. Most preferably, R1 is hydrogen.
Preferably, R2 is hydrogen, methyl, ethyl or acetyl. More preferably, R2 is hydrogen, methyl or ethyl. Most preferably, R2 is hydrogen.
Preferably, R5 is trifiuoromethyl, pentafluoroethyl or heptafluoroprop-2-yl. Most preferably, R5 is trifiuoromethyl. Preferably, Q1 is aryl or heteroaryl; each optionally substituted by one to five substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl and phenyl.
More preferably, Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl; each optionally substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl and phenyl.
Even more preferably, Q1 is phenyl, pyridyl or furanyl; each optionally substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl and phenyl.
Most preferably, Q1 is phenyl or furan-2-yl; each optionally substituted by one, two or three substituents independently selected from cyano, nitro, chloro, fluoro, methyl, trifluoromethyl, methoxy and trifluoromethoxy.
Representative Q1 substituents are selected from the substituents of Table 1.
Table 1
Figure imgf000282_0001
Figure imgf000283_0001
Preferably, Q2 is aryl or heteroaryl; each optionally substituted by one to five substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy and trifluoromethoxy.
More preferably, Q2 is phenyl, pyridyl, furanyl, thiophenyl or thiazolyl; each optionally substituted by one to three substituents independently selected from chloro, fluoro, methyl, trifluoromethyl, methoxy and trifluoromethoxy.
Most preferably, Q2 is phenyl or thiophenyl; each optionally substituted by one, two or three substituents independently selected from chloro, fluoro, methyl, trifluoromethyl, methoxy and trifluoromethoxy.
Representative Q2 substituents are selected from the substituents of Table 2.
Table 2
Figure imgf000283_0002
Figure imgf000284_0001
In a preferred aspect of the invention, A1, A2, A3 and A4 are CH.
In another preferred aspect of the invention, A1 is C-F and A2, A3 and A4 are CH.
In a further preferred aspect of the invention, A2 is C-F and A1, A3, and A4 are CH.
In a further preferred aspect of the invention, A3 is C-F and A1, A2, and A4 are CH.
In a further preferred aspect of the invention, A4 is C-F and A1, A2, and A3 are CH.
In a further preferred aspect of the invention, A1 is C-CN and A2, A3, and A4 are CH.
In a further preferred aspect of the invention, A4 is C-OCH3 and A1, A2, and A3 are CH. In a first preferred embodiment of the embodiment (M) of the invention A1, A2, A3 and A 4 are CH; R 1 and R2z are hydrogen; R 5 is trifluoromethyl; G 1 and G2 are oxygen; Y 2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl.
In a second preferred embodiment of the embodiment (M) of the invention A1 is C- CN and A2, A3, and A4 are CH; R1 and R2 are hydrogen; R5 is trifluoromethyl; G1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl.
In a third preferred embodiment of the embodiment (M) of the invention A4 is C- OCH3 and A1, A2, and A3 are CH; R1 and R2 are hydrogen; R5 is trifluoromethyl; G1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl.
In a fourth preferred embodiment of the embodiment (M) of the invention A4 is C-F and A 1 , A2 , and A3 are CH; R 1 and R2 are hydrogen; R 5 is trifluoromethyl; G 1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl. In a fifth preferred embodiment of the embodiment (M) of the invention A1, A2, A3 and A 4 are CH; R 1 and R2z are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y 2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl.
In a sixth preferred embodiment of the embodiment (M) of the invention A1 is C-CN and A 2 , A3 , and A4 are CH; R 1 and R2 are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl.
In a seventh preferred embodiment of the embodiment (M) of the invention A4 is C- OCH3 and A1 , A2, and A3 are CH; R1 and R2 are hydrogen; R5 is trifiuoromethyl; G1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl.
In an eighth preferred embodiment of the embodiment (M) of the invention A4 is C-F and A 1 , A2 , and A3 are CH; R 1 and R2 are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is selected from the substituents of Table 1; and Q2 is 4-chlorophenyl.
In a ninth preferred embodiment of the embodiment (M) of the invention A1, A2, A3 and A 4 are CH; R 1 and R2z are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y 2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is 2,4,6-trifluorophenyl; and Q2 is selected from the substituents of Table 2.
In a tenth preferred embodiment of the embodiment (M) of the invention A1 is C-CN and A 2 , A3 , and A4 are CH; R 1 and R2 are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is 2,4,6-trifluorophenyl; and Q2 is selected from the substituents of Table 2.
In a eleventh preferred embodiment of the embodiment (M) of the invention A4 is C-
OCH3 and A1, A2, and A3 are CH; R1 and R2 are hydrogen; R5 is trifiuoromethyl; G1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is 2,4,6-trifluorophenyl; and Q2 is selected from the substituents of Table 2.
In a twelth preferred embodiment of the embodiment (M) of the invention A4 is C-F and A 1 , A2 , and A3 are CH; R 1 and R2 are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are methyl; Q1 is 2,4,6-trifluorophenyl; and Q2 is selected from the substituents of Table 2. In a thirteenth preferred embodiment of the embodiment (M) of the invention A1, A2,
A 3 and A 4 are CH; R 1 and R2 are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y 2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is 2,4,6-trifiuorophenyl; and Q2 is selected from the substituents of Table 2.
In a fourteenth preferred embodiment of the embodiment (M) of the invention A1 is
C-CN and A2, A3, and A4 are CH; R1 and R2 are hydrogen; R5 is trifiuoromethyl; G1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is 2,4,6-trifiuorophenyl; and Q2 is selected from the substituents of Table 2.
In a fifteenth preferred embodiment of the embodiment (M) of the invention A4 is C- OCH3 and A1 , A2, and A3 are CH; R1 and R2 are hydrogen; R5 is trifiuoromethyl; G1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is 2,4,6-trifiuorophenyl; and Q2 is selected from the substituents of Table 2.
In an sixteenth preferred embodiment of the embodiment (M) of the invention A4 is
C-F and A 1 , A2 , and A3 are CH; R 1 and R2 are hydrogen; R 5 is trifiuoromethyl; G 1 and G2 are oxygen; Y2 and Y3 are hydrogen; Y1 and Y4 are chloro; Q1 is 2,4,6-trifiuorophenyl; and Q2 is selected from the substituents of Table 2.
Most preferred compounds of formula (I) according to the embodiment (M) are those of the folio wingExamples:
3-[(4-fluorobenzoyl)amino]-N- {2,6-dimethyl-4-[ 1 -(4-trifluoromethyl-phenyl)-2,2,2-trifluoro- l-fluoroethyl]phenyl}benzamide (compound Al)
3-[(benzoyl)amino]-N- {2,6-dichloro-4-[ 1 -(4-chlorophenyl)-2,2,2-trifluoro- 1 -fluoroethyl]-2- methoxyphenyl}benzamide
3-[(benzoyl)amino]-2-methoxy-N- {2,6-dichloro-4-[ 1 -(4-chloro-phenyl)-2,2,2-trifluoro- 1 - hydroxyethyl]-2-methoxyphenyl}benzamide
3- [benzoylamino]-2-methoxy-N- {2,6-dichloro-4-[ 1 -(4-chlorophenyl)-2,2,2-trifluoro- 1 - N-{3-[2,6-dichloro-4-(2,2,2-trifluoro-l-fluoro-l-thiophen-2-yl-ethyl)phenylcarbamoyl]-2- fluorophenyl}-2,4,6-trifluorobenzamide
N-{3-[2,6-dichloro-4-(2,2,2-trifluoro-l-fluoro-l-thiophen-2-ylethyl)-phenylcarbamoyl]-2- fluorophenyl} -2,4,6-trifluorobenzamide(compound A4)
N-{3-[2,6-dichloro-4-(2,2,2-trifluoro-l-fluoro-l-(4-chloro-phenyl)ethyl)phenylcarbamoyl]-
4- cyanophenyl}-2-chloro-4-fluorobenzamide Or a compound according to the Table A Table A: Compounds of formula (la):
Figure imgf000287_0001
Figure imgf000288_0001
Figure imgf000289_0001
Figure imgf000290_0001
In an embodiment (N), the invention relates to a pharmaceutical composition comprising at least one compound of formula (I)
Figure imgf000290_0002
wherein
A1, A2, A3 and A4 are each independently C-X or nitrogen, wherein each X may be the same or different, and provided that no more than two of A1, A2, A3 and A4 are nitrogen;
R1 is hydrogen, d-C4alkyl, Ci-C4alkyl-C(0)NH2, or d-C4alkylcarbonyl;
R2 is hydrogen, halogen, Ci-C4alkyl„ Ci-C4alkyl-C(0)NH2, Ci-C6 haloalkyl or cyano;
G1 is oxygen or sulfur; X is hydrogen, halogen, cyano, Ci-C4alkyloxy, Ci-C4alkyl or Ci-C4haloalkyl;
Q1 is aryl or heterocyclyl, each optionally substituted by one to five R3 substituents, which may be the same or different;
R3 is selected from cyano, amino, nitro, hydroxy, halogen, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C2-C4haloalkynyl, C3-C6cycloalkyl,
C3-C6halocycloalkyl, Ci-C3alkoxy, Ci-Cshaloalkoxy, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl, Ci-C3haloalkylsulfonyl, Ci-C4alkylamino, di-(Ci-C4alkyl)amino, Ci-C4alkylcarbonyl, Ci-C4alkylcarbonyloxy, Ci-C4alkoxycarbonyl, Ci-C4alkylcarbonylamino and phenyl;
Q2 is a moiety of formula (A) or (B)
Figure imgf000291_0001
Y1 and Y5 are each independently selected from hydrogen, cyano, halogen, Ci-C4alkyl, Ci- C4haloalkyl, Ci-C4alkoxy-Ci-C4alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci- C3alkylsulfinyl, Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl and Ci-C3haloalkylsulfonyl; Y3 is Ci-C6perfluoroalkyl, Ci-Ceperfluoroalkylthio, Ci-Ceperfluoroalkylsulfinyl or
C i -Ceperfluoroalkylsulfonyl;
Y2 and Y4 are each independently selected from hydrogen, halogen and Ci-C4alkyl;
Y6 and Y9 are each independently selected from cyano, halogen, Ci-C4alkyl, Ci-C4haloalkyl,
Ci-C4alkoxy-Ci-C4alkyl, Ci-C3alkylthio, Ci-C3haloalkylthio, Ci-C3alkylsulfinyl,
Ci-C3haloalkylsulfinyl, Ci-C3alkylsulfonyl and Ci-C3haloalkylsulfonyl;
Y8 is Ci-C4haloalkoxy, C2-C6perfiuoroalkyl, Ci-C6perfluoroalkylthio, Ci-C6perfluoroalkyl- sulfinyl or Ci-C6perfluoroalkylsulfonyl;
Y7 is hydrogen, halogen or Ci-C4alkyl;
or an agrochemically acceptable salt or N-oxides thereof
for preventing infection with diseases transmitted through parasites and controlling of parasites on and in animals and humans. In the embodiment (N) the preferred values of A1, A2, A3, A4, R1, R2, R3, G1, X, Q1, Q2, Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8 and Y9 are, in any combination, as set out below.
Preferably A1 is C-X.
Preferably A2 is C-X.
Preferably A3 is C-X.
Preferably A4 is C-X.
Preferably, X is hydrogen, halogen, cyano, methyl, trifluoromethyl or methoxy. More preferably, X is hydrogen, fluoro, chloro, cyano, trifluoromethyl or methoxy. Even more preferably, X is hydrogen, fluoro, cyano or methoxy. Most preferably, X is hydrogen, fluoro or cyano.
More preferably, A1, A2, A3 and A4 are C-X and each X is independently selected from hydrogen, halogen, cyano, methyl, trifluoromethyl and methoxy. Even more preferably, A1, A2, A3 and A4 are C-X and each X is independently selected from hydrogen, fluoro, cyano and methoxy. Most preferably, A1 is CH, C-CN or C-F; and A2, A3 and A4 are CH.
Preferably, G1 is oxygen.
Preferably, R1 is hydrogen, methyl, ethyl or acetyl. More preferably, R1 is hydrogen, methyl or ethyl. Most preferably, R1 is hydrogen.
Preferably, R2 is hydrogen, methyl, trifluoromethyl or halogen. More preferably, R2 is hydrogen, trifluoromethyl or halogen. Even more preferably, R2 is hydrogen or halogen. Most preferably, R2 is hydrogen.
Preferably, Q1 is aryl or heteroaryl; each optionally substituted by one to five substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl,
methylsulfonyl and phenyl.
More preferably, Q1 is phenyl, pyridyl, furanyl, thiophenyl, pyrazolyl or 1,2,3- thiadiazolyl; each optionally substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio, methylsulfmyl, methylsulfonyl and phenyl.
Even more preferably, Q1 is phenyl, pyridyl or furanyl; each optionally substituted by one to four substituents independently selected from cyano, nitro, hydroxy, bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio,
methylsulfmyl, methylsulfonyl and phenyl. Most preferably, Q1 is phenyl or pyridyl; each optionally substituted by one, two or three substituents independently selected from cyano, nitro, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
Preferred examples of Q1 include phenyl, 5-bromofuran-2-yl, 2-methoxyphenyl, 2-bromophenyl, 2-methylphenyl, 5-bromopyrid-3-yl, 3-methylpyrid-2-yl, 2-chloro-4- fluorophenyl, 4-methyl-l,2,3-thiadiazol-5-yl, 3-chloro-2-fluorophenyl, 4-nitrophenyl,
5- chloro-2-fluorophenyl, 3-chloro-2-methylphenyl, l,2,3-thiadiazol-4-yl, 2-chloro-4- nitrophenyl, thiophen-2-yl, 2-chloro-5-nitrophenyl, 2-(trifluoromethoxy)phenyl,
2-chlorophenyl, 4-(trifluoromethoxy)phenyl, 3-chlorophenyl, 2-(trifluoromethyl)phenyl,
2- chloropyrid-3-yl, 4-(trifluoromethyl)phenyl, 2-chloropyrid-4-yl, 2-methyl-4-cyanophenyl,
6- chloropyrid-3-yl, 2,4,6-trifluorophenyl, 5-chlorothiophen-2-yl, 2,6-difluorophenyl,
3- chloro-5-(trifluoromethyl)pyrid-2-yl, 2,6-difluoro-4-cyanophenyl, 4-cyano-2-fluorophenyl, 2-chloro-6-fluorophenyl, 4-cyanophenyl, 2-methyl-3-nitrophenyl, 2-methyl-4-nitrophenyl, 2,5-dichlorophenyl, 3-methyl-4-nitrophenyl, 2,3-difluorophenyl, 2-chloro-4-cyanophenyl, l,3-dimethyl-lH-pyrazol-5-yl, 2-fluoro-4-cyanophenyl, 2-fluorophenyl, 4-methylthiophenyl,
4- fluorophenyl, l-methyl-3-(trifluoromethyl)pyrazol-4-yl, 2-fluoropyrid-3-yl, 4-pyridyl, 2-fluoro-3-(trifluoromethyl)phenyl, 1 ,3-dimethylpyrazol-4-yl, 2-fluoro-5-(trifluoromethyl)- phenyl, 4-methylphenyl, 4-fluoro-3-(trifluoromethyl)phenyl, 4-fluoro-2-methylphenyl, furan-2-yl, and 2,4-difluorophenyl.
Preferably, Y1 is hydrogen, cyano, fluoro, chloro, bromo, methyl, ethyl,
trifluoromethyl or methoxymethyl. More preferably, Y1 is chloro, bromo, methyl, ethyl, or trifluoromethyl. Most preferably, Y1 is chloro.
Preferably, Y2 is hydrogen, fluoro, chloro or methyl. Most preferably, Y2 is hydrogen.
Preferably, Y3 is heptafluoropropyl, nonafluorobutyl, heptafluoropropylthio, heptafluoropropylsulfinyl, or heptafluoropropylsulfonyl. More preferably, Y3 is
heptafluoroprop-l-yl, heptafluoroprop-2-yl, nonafluorobut-2-yl, heptafluoroprop-l-ylthio, heptafluoroprop- 1 -ylsulfinyl, heptafluoroprop- 1 -ylsulfonyl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, or heptafluoroprop-2-ylsulfonyl. Even more preferably, Y3 is heptafluoroprop- 1-yl, heptafluoroprop-2-yl, nonafluorobut-2-yl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, or heptafluoroprop-2-ylsulfonyl. Most preferably, Y3 is heptafluoroprop-2-yl or nonafluorobut-2-yl.
Preferably, Y4 is hydrogen, fluoro, chloro or methyl. Most preferably, Y4 is hydrogen. Preferably, Y5 is hydrogen, cyano, fluoro, chloro, bromo, methyl, ethyl,
trifiuoromethyl or methoxymethyl. More preferably, Y5 is chloro, bromo, methyl, ethyl or trifluoromethyl. Most preferably, Y5 is chloro.
Preferably, Y6 is hydrogen, cyano, fluoro, chloro, bromo, methyl, ethyl,
trifiuoromethyl or methoxymethyl.
Preferably, Y7 is hydrogen, fluoro, chloro or methyl.
Preferably, Y8 is heptafluoropropyl, nonafluorobutyl, heptafluoropropylthio, heptafluoropropylsulfinyl, or heptafluoropropylsulfonyl. Most preferably, Y8 is
heptafluoroprop-l-yl, heptafluoroprop-2-yl, nonafluorobut-2-yl, heptafluoroprop-2-ylthio, heptafluoroprop-2-ylsulfinyl, or heptafluoroprop-2-ylsulfonyl.
Preferably Y9 is bromo, chloro, methyl, ethyl or trifluoromethyl.
Preferably, Q2 is a moiety of formula (A).
More preferably, Q2 is 4-heptafluoroisopropyl-2,6-dimethylphenyl,
4-heptafluoroisopropyl-2-methyl-6-ethylphenyl, 4-heptafluoroisopropyl-2,6-diethylphenyl, 4-heptafluoroisopropyl-2-methoxymethyl-6-methylphenyl, 4-heptafluoroisopropyl- 2,6-dichlorophenyl, 4-heptafluoroisopropyl-2,6-dibromophenyl, 4-heptafluoroisopropyl- 2-chloro-6-bromophenyl, 4-heptafluoroisopropyl-2-ethyl-6-bromophenyl,
4-heptafluoroisopropyl-2-methyl-6-bromophenyl, 4-heptafluoroisopropyl-2-bromo-6- ethylphenyl, 4-( 1 ,2,2,3,3,3 -hexafluoro- 1 -(trifluoromethyl)propyl)-2,6-dimethylphenyl, 4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2-methyl-6-ethylphenyl,
4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2,6-diethylphenyl,
4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2-methoxymethyl-6-methylphenyl, 4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2,6-dichlorophenyl,
4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2,6-dibromophenyl,
4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2-chloro-6-bromophenyl,
4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2-ethyl-6-bromophenyl,
4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2-bromo-6-methylphenyl, or
4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2-bromo-6-ethylphenyl.
Most preferably, Q2 is 4-heptafluoroisopropyl-2,6-dichlorophenyl,
4-heptafluoroisopropyl-2-methyl-6-bromophenyl, 4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifluoromethyl)propyl)-2-methyl-6-ethylphenyl, or 4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 - (trifluoromethyl)propy l)-2 ,6 -dichloropheny 1. In a preferred aspect of the invention, A1, A2, A3 and A4 are CH.
In a further preferred aspect of the invention, A4 is C-F and A1, A2, and A3 are CH.
In a further preferred aspect of the invention, A1 is C-CN and A2, A3, and A4 are CH.
In a further preferred aspect of the invention, A4 is C-OCH3 and A1, A2, and A3 are CH. In a further preferred aspect of the invention, A1 is C-F and A2, A3, and A4 are CH.
In a first preferred embodiment of the embodiment (N) of the invention, A1, A2, A3 and A4 are CH; R1 and R2 are hydrogen; G1 is oxygen; Q1 is 2-fluorophenyl; Q2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
Table 1
Figure imgf000295_0001
In a second preferred embodiment of the embodiment (N) of the invention, A1, A2, A3 and A4 are CH; R1 and R2 are hydrogen; G1 is oxygen; Q1 is 2-chloropyrid-3-yl; Q2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In a third preferred embodiment of the embodiment (N) of the invention, A1, A2, A3 and A are CH; R1 and R2 are hydrogen; G1 is oxygen; Q1 is 2-chloro-4-fluorophenyl; Q2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In a fourth preferred embodiment of the embodiment (N) of the invention, A1, A2, A3 and A4 are CH; R1 and R2 are hydrogen; G1 is oxygen; Q1 is 4-cyanophenyl; Q2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In a fifth preferred embodiment of the embodiment (N) of the invention, A1, A2, A3 and A4 are CH; R1 and R2 are hydrogen; G1 is oxygen; Q1 is 4-fluorophenyl; Q2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In a sixth preferred embodiment of the embodiment (N) of the invention, A1, A2, A3 and A4 are CH; R1 and R2 are hydrogen; G1 is oxygen; Q1 is 2-methylphenyl; Q2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In a seventh preferred embodiment of the embodiment (N) of the invention, A1, A2, A 3 and A 4 are CH; R 1 and R2 are hydrogen; G 1 is oxygen; Q1 is 4-fluoro-2-methylphenyl; Q 2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In an eighth preferred embodiment of the embodiment (N) of the invention, A1, A2,
A 3 and A 4 are CH; R 1 and R2 are hydrogen; G 1 is oxygen; Q1 is 2-methyl-3-nitrophenyl; Q 2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In a ninth preferred embodiment of the embodiment (N) of the invention, A1 is C-CN;
A 2 , A 3 , and A 4 are CH; R 1 and R 2 are hydrogen; G 1 is oxygen; Q 1 is 2-methyl-4- cyanophenyl; Q2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
In a tenth preferred embodiment of the embodiment (N) of the invention, A1 is C-F;
A 2 , A3 , and A4 are CH; R1 and R2 are hydrogen; G 1 is oxygen; Q 1 is 2,4,6-trifluorophenyl; Q 2 is a moiety of formula (A); and Y1, Y3 and Y5 are represented by substituent combinations 1.01 to 1.16 of Table 1.
The following compounds illustrate the preferred compounds of the invention according to the embodiment (N)
2-Amino-4-{l-[2,6-dichloro-4-(l, 2,2,3, 3,3-hexafiuoro-l-(trifiuoromethyl)-propyl)phenyl]- lH-l,2,3-triazol-4-yl}benzonitrile ( Compound B6)
4-cyano-N-(3 - { 1 -[2,6-dichloro-4-( 1 ,2,2,3 ,3 ,3-hexafluoro- 1 -(trifiuoromethyl)-propyl)phenyl]- lH-l,2,3-triazol-4-yl}phenyl)benzamide (Compound Al)
N-(3 - { 1 -[2-Bromo-6-ethyl-4-( 1 ,2,2,2-tetrafluoro- 1 -trifluoromethyl-ethyl)-phenyl] - 1 Η- [l,2,3]triazol-4-yl}-phenyl)-2-fluoro-benzamide (Compound A20)
Or a compound according to the Table A or Table B or Table C:
Table A: Compounds of formula (Ie): R2 = Η and A4 = CH
Figure imgf000297_0001
Ex. Q1 Y3 Y1 Y5 A1
Al 4-cyanophenyl nonafluoro-but-2-yl CI CI CH
A2 2-chloro-4-fluorophenyl nonafluoro-but-2-yl CI CI CH
A3 4-fluorophenyl nonafluoro-but-2-yl CI CI CH
A4 2-fluorophenyl nonafluoro-but-2-yl CI CI CH
2-chloro-
A5 nonafluoro-but-2-yl CI CI CH
pyridin-3-yl
A6 2-methyl-phenyl nonafluoro-but-2-yl CI CI CH
A7 2-methyl-4-fluorophenyl nonafluoro-but-2-yl CI CI CH
A8 2-methyl-3 -nitrophenyl nonafluoro-but-2-yl CI CI CH
Figure imgf000298_0001
Figure imgf000299_0001
Figure imgf000300_0001
Figure imgf000301_0001
Figure imgf000302_0001
Figure imgf000303_0001
Figure imgf000304_0001
Figure imgf000305_0001
Table B: Compound of formula (Ig): R2 = H
Figure imgf000305_0002
Compound
Y3 Y1 Y5 A1 A4 No.
Bl nonafluoro-but-2 -yl CI CI CH CH
B2 heptafluoro-prop-2-yl Me Br CH CH
B3 heptafluoro-prop-2-yl CI CI CH CH
B4 nonafluoro-but-2 -yl Me Et CH CH
B5 nonafluoro-but-2 -yl CI CI C-F CH
B6 nonafluoro-but-2 -yl CI CI C-CN CH
B7 heptafluoro-prop-2-yl Me H CH CH
B8 heptafluoro-prop-2-yl Et Br CH CH
B9 nonafluoro-but-2 -yl CI CI C-H C-F
BIO heptafluoro-prop-2-yl CI CI C-CN CH
Bl l nonafluoro-but-2 -yl Et Br CH CH
B12 nonafluoro-but-2 -yl Me Br CH CH
B13 trifluoromethyl CI CI CH CH Table C: Compound of formula (le): R2 = H and A1 = CH
Figure imgf000306_0001
(le)
Figure imgf000306_0002
4- nonafiuoro-
Cl l trifiuorometho CI CI C-F but-2-yl
xy-Phenyl
3- trifiuoromethyl nonafiuoro-
C12 CI CI C-F
-4-fiuoro- but-2-yl
Phenyl
3- nonafiuoro-
C13 trifiuoromethyl CI CI C-F but-2-yl
-Phenyl
2- nonafiuoro-
C14 trifiuorometho CI CI C-F but-2-yl
xy-Phenyl
2-methoxy- nonafiuoro-
C15 CI CI C-F
Phenyl but-2-yl
nonafiuoro-
C16 Phenyl CI CI C-F but-2-yl
4-fiuoro- nonafiuoro-
C17 CI CI C-F
Phenyl but-2-yl
2- nonafiuoro-
C18 trifiuoromethyl CI CI C-F but-2-yl
-Phenyl
4-fiuoro-2- nonafiuoro-
C19 CI CI C-F chloro-Phenyl but-2-yl
4-Methyl- nonafiuoro-
C20 [l,2,3]thiadiaz CI CI C-F but-2-yl
ole
2, 3 -difiuoro- nonafiuoro-
C21 CI CI C-F
Phenyl but-2-yl
2, 4 -difiuoro- nonafiuoro-
C22 CI CI C-F
Phenyl but-2-yl 2-fluoro-5- nonafluoro-
C23 trifluoromethyl CI CI C-F
but-2-yl
-Phenyl
The compound of the of the present invention thus from the embodiments embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M), and/or embodiment (N) are known from
WO2007128410, WO2008000438, WO2008012027, WO2008031534, WO2008074427, WO2008107091, WO2009049845, WO2009049844, WO2010006725, WO2010127928, WO2010127927, WO2010127926, WO2011095462 and WO2011113756
The following embodiments and apply to all the above mentioned embodiments of the present invention, especially of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or embodiment (N): Further to this "a compound of formula (I*)" or "compounds of formula (I*)" means compounds according to one of the embodiments of the present invention, especially compounds of the embodiment (A),compounds of the embodiment (B), compounds of the embodiment (C), compounds of the embodiment (D), compounds of the embodiment (E), embodiment (F), compounds of the embodiment (G), compounds of the embodiment (H), embodiment (I), compounds of the embodiment (J), compounds of the embodiment (K), compounds of the embodiment (L), compounds of the embodiment (M) and/or, compounds of the embodiment (N) or a specific compound listed in the embodiment (A), a specific compound listed in the embodiment (B), a specific compound listed in the embodiment (C), embodiment (D), a specific compound listed in the embodiment (E),a specific compound listed in the embodiment (F), a specific compound listed in the embodiment (G), a specific compound listed in the embodiment (H), a specific compound listed in the embodiment (I), embodiment (J), a specific compound listed in the embodiment (K), a specific compound listed in the embodiment (L), a specific compound listed in the embodiment (M) and/or, a specific compound listed in the embodiment (N).
Further to this TX means a compound where "TX" means a compound described by the formula (I) as set forth in the embodiment (A), "TX" means a compound described by the formula (I) as set forth in the embodiment (B), „TX" means a compound described by the formula (I) as set forth in the embodiment (C), „TX" means a compound described by the formula (I) as set forth in the embodiment (D), „TX" means a compound described by the formula (I) as set forth in the embodiment (E), „TX" means a compound described by the formula (I) as set forth in the embodiment (F), „TX" means a compound described by the formula (I) as set forth in the embodiment (G), „TX" means a compound described by the formula (I) as set forth in the embodiment (H), „TX" means a compound described by the formula (I) as set forth in the embodiment (I), , ,TX" means a compound described by the formula (I) as set forth in the embodiment (J), , ,TX" means a compound described by the formula (I) as set forth in the embodiment (K), „TX" means a compound described by the formula (I) as set forth in the embodiment (L), „TX" means a compound described by the formula (I) as set forth in the embodiment (M) and/or„TX" means a compound described by the formula (I) as set forth in the embodiment (N), and in particular TX is a specific compound listed in the embodiment (A), TX is a specific compound listed in the
embodiment (B), TX is embodiment (C), TX is a specific compound listed in the
embodiment (D), TX is a specific compound listed in the embodiment (E), TX is a specific compound listed in the embodiment (F), TX is a specific compound listed in the embodiment (G), TX is a specific compound listed in the embodiment (H), TX is a specific compound listed in the embodiment (I), TX is a specific compound listed in the embodiment (J), TX is a specific compound listed in the embodiment (K), TX is a specific compound listed in the embodiment (L), TX is a specific compound listed in the embodiment (M) and/or, TX is a specific compound listed in the embodiment (N).
The invention further relates to a pharmaceutical composition comprising at least one compound of formula (I) of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M)and/or embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M)and/or, embodiment (N) for preventing infection with diseases transmitted through parasites andcontrolling of parasites on and in animals and humans.
The invention further relates to a method of controlling parasitic invertebrate pests in or on an animal comprising administering an effective amount of TX to the animal or human wherein preferably the administration oral administration, parenteral administration or external administration.
The invention further relates to a method of controlling parasitic invertebrate pests comprising administering an effective amount of TX to the environment in which an animal or an human resides.
The invention further relates to TX for use for preventing infection with diseases transmitted through parasites andcontrolling of parasites on and in animals and humans.
The invention further relates pharmaceutical composition comprising at least one compound of formula (I) of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) for use against parasitic invertebrate pests in or on an animal or in or on a human.
Preferrably the pest is a nematode, a trematode, a cestode, a fly, a mite, a trick, a lice, a flea, a true bug or a maggot. Preferrably the animal to be treated is a cow, a pig, a sheep, a goat, a dog, a cat, a horse, and/or a donkey.
The invention further relates to a method comprising administering the pharmaceutical composition as defined above to an animal.
The invention further relates to a method of controlling parasitic invertebrate pests in or on an animal comprising administering an effective amount of the pharmaceutical composition as defined in claim 1 to the animal. Preferably the administration is oral administration, parenteral administration or external administration.
The invention further relates to a method method of controlling parasitic invertebrate pests comprising administering an effective amount of the pharmaceutical composition as defined in claim 1 to the environment in which an animal resides.
The invention further relates to a pharmaceutical composition comprising component A and component B and a pharmaceutically suitable excipient wherein the component A is at least one compound of formula (I) of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and the component B is a further therapeutic agent.
In one embodiment the pharmaceutical composition composition according to the invention, the component B is imidacloprid, enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, fipronil, ivermectin, omeprazole, tiamulin, benazepril, milbemycin, cyromazine, thiamethoxam, pyriprole, deltamethrin, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, metaflumizone, moxidectin, methoprene (including S- methoprene), clorsulon, pyrantel, amitraz, triclabendazole, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, fipronil, lufenuron, ecdysone or tebufenozide. In one embodiment the pharmaceutical composition composition according to the invention, the component B is enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, moxidectin, clorsulon, pyrantel, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, lufenuron or ecdysone.
In one embodiment the pharmaceutical composition composition according to the invention, the component B is enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, moxidectin, clorsulon or pyrantel. A futher aspect of the present invention is the use of a compound of formula (I) of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M)and/or, embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) against parasitic invertebrate pests in or on an animal or in or on a human.
The compounds of formula (I*) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests. The pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
Examples of pest species which may be controlled by the compounds of formula (I*) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.
(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa
decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (white flies), Bemisia tabaci (white fly), Ostrinia nubilalis (European corn borer), Spodoptera littoralis (cotton leafworm), Heliothis virescens (tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pieris brassicae (white butterfly), Plutella xylostella (diamond back moth), Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta migratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp. (rootworms), Panonychus ulmi (European red mite), Panonychus citri (citrus red mite), Tetranychus urticae (two-spotted spider mite), Tetranychus cinnabarinus (carmine spider mite),
Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpus spp. (flat mites), Boophilus microplus (cattle tick), Dermacentor variabilis (American dog tick), Ctenocephalides felis (cat flea), Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti (mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes), Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplaneta americana (cockroach), Blatta orientalis (cockroach), termites of the Mastotermitidae (for example Mastotermes spp.), the Kalotermitidae (for example Neotermes spp.), the
Rhinotermitidae (for example Coptotermes formosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R. hesperus, and R. santonensis) and the Termitidae (for example Globitermes sulfureus), Solenopsis geminata (fire ant), Monomorium pharaonis (pharaoh's ant),
Damalinia spp. and Linognathus spp. (biting and sucking lice), Meloidogyne spp. (root knot nematodes), Globodera spp. and Heterodera spp. (cyst nematodes), Pratylenchus spp.
(lesion nematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulus spp. (citrus nematodes), Haemonchus contortus (barber pole worm), Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastro intestinal nematodes) and Deroceras reticulatum (slug).
The invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I*), or a composition containing a compound of formula (I*), to a pest, a locus of pest, preferably a plant, or to a plant susceptible to attack by a pest or a plant propagation material. The compounds of formula (I*) are preferably used against insects, acarines or nematodes.
As for acari, for example, Tetranychus cinnabarinus, Tetranychus urticae,
Panonychus citri, Aculops pelekassi, Tarsonemus spp..
As for nematodes, for example, Meloidogyne incognita, Bursaphelenchus lignicolus Mamiya et Kiyohara, Aphelenchoides besseyi, Heterodera glycines, Pratylenchus spp..
Additionally, the compounds can be used for controlling animal pests, in particular insects, arachnids, helminths, nematodes and molluscs, which are encountered in agriculture, in horticulture, the field of veterinary medicine, in forests, in gardens and leisure facilities, in the protection of stored products and of materials, and in the hygiene sector. They may preferably be employed as plant protection agents. They may be active against normally sensitive and resistant species and against all or some stages of development.
These pests include inter alia:
From the order of the Anoplura (Phthiraptera), for example, Damalinia spp.,
Haematopinus spp., Linognathus spp., Pediculus spp., Trichodectes spp..
From the class of the Arachnida, for example, Acarus siro, Aceria sheldoni, Aculops spp., Aculus spp., Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Chorioptes spp., Dermanyssus gallinae, Eotetranychus spp., Epitrimerus pyri, Eutetranychus spp., Eriophyes spp., Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Latrodectus mactans, Metatetranychus spp., Oligonychus spp., Ornithodoros spp.,
Panonychus spp., Phyllocoptruta oleivora, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus, Stenotarsonemus spp., Tarsonemus spp., Tetranychus spp., Vasates lycopersici.
From the class of the Bivalva, for example, Dreissena spp..
From the order of the Chilopoda, for example, Geophilus spp., Scutigera spp.. From the order of the Coleoptera, for example, Acanthoscehdes obtectus, Adoretus spp., Agelastica alni, Agriotes spp., Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp., Anthrenus spp., Apogonia spp., Atomaria spp., Attagenus spp., Bruchidius obtectus, Bruchus spp., Ceuthorhynchus spp., Cleonus mendicus, Conoderus spp., Cosmopolites spp., Costelytra zealandica, Curculio spp., Cryptorhynchus lapathi, Dermestes spp., Diabrotica spp., Epilachna spp., Faustinus cubae, Gibbium psylloides, Heteronychus arator, Hylamorpha elegans, Hylotrupes bajulus, Hypera postica, Hypothenemus spp., Lachnosterna consanguinea, Leptinotarsa decemlineata, Lissorhoptrus oryzophilus, Lixus spp., Lyctus spp., Meligethes aeneus, Melolontha melolontha, Migdolus spp., Monochamus spp., Naupactus xanthographus, Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Otiorrhynchus sulcatus, Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Popillia japonica, Premnotrypes spp., Psylliodes
chrysocephala, Ptinus spp., Rhizobius centralis, Rhizopertha dominica, Sitophilus spp., Sphenophorus spp., Sternechus spp., Symphyletes spp., Tenebrio molitor, Tribolium spp., Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp..
From the order of the Collembola, for example, Onychiurus armatus.
From the order of the Dermaptera, for example, Forficula auricularia.
From the order of the Diplopoda, for example, Blaniulus guttulatus.
From the order of the Diptera, for example, Aedes spp., Anopheles spp., 5z'¾z'o hortulanus, Calliphora erythrocephala, Ceratitis capitata, Chrysomyia spp., Cochliomyia spp., Cordylobia anthropophaga, Culex spp., Cuterebra spp., Dacus oleae, Dermatobia hominis, Drosophila spp., Fannia spp., Gastrophilus spp., Hylemyia spp., Hyppobosca spp., Hypoderma spp., Liriomyza spp., Lucilia spp., Musca spp., Nezara spp., Oestrus spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Stomoxys spp., Tabanus spp., Tannia spp., Tipula paludosa, Wohlfahrtia spp..
From the class of the Gastropoda, for example, ^non spp., Biomphalaria spp., Bulinus spp., Deroceras spp., Galba spp., Lymnaea spp., Oncomelania spp., Succinea spp..
From the class of the helminths, for example, Ancylostoma duodenale, Ancylostoma ceylanicum, Acylostoma braziliensis, Ancylostoma spp., Ascaris lubricoides, Ascaris spp., Brugia malayi, Brugia timori, Bunostomum spp., Chabertia spp., Clonorchis spp., Cooperia spp., Dicrocoelium spp, Dictyocaulus filaria, Diphyllobothrium latum, Dracunculus medinensis, Echinococcus granulosus, Echinococcus multilocularis, Enterobius
vermicularis, Faciola spp., Haemonchus spp., Heterakis spp., Hymenolepis nana,
Hyostrongulus spp., Zoa Zoa, Nematodirus spp., Oesophagostomum spp., Opisthorchis spp., Onchocerca volvulus, Ostertagia spp., Paragonimus spp., Schistosomen spp., Strongyloides fuelleborni, Strongyloides stercoralis, Stronyloides spp., Taenia saginata, Taenia solium, Trichinella spiralis, Trichinella nativa, Trichinella britovi, Trichinella nelsoni, Trichinella pseudopsiralis, Trichostrongulus spp., Trichuris trichuria, Wuchereria bancrofti.
It may be furthermore possible to control protozoa, such as Eimeria.
From the order of the Heteroptera, for example, Anasa tristis, Antestiopsis spp.,
Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp.,
Euschistus spp., Eurygaster spp., Heliopeltis spp., Horcias nobilellus, Leptocorisa spp., Leptoglossus phyllopus, Lygus spp., Macropes excavatus, Miridae, Nezara spp., Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp., Psallus seriatus, Pseudacysta persea, Rhodnius spp., Sahlbergella singularis, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp..
From the order of the Homoptera, for example, Acyrthosipon spp., Aeneolamia spp., Agonoscena spp., Aleurodes spp., Aleurolobus barodensis, Aleurothrixus spp., Amrasca spp., Anuraphis cardui, Aonidiella spp., Aphanostigma piri, Aphis spp., Arboridia apicalis, Aspidiella spp., Aspidiotus spp., Atanus spp., Aulacorthum solani, Bemisia spp.,
Brachycaudus helichrysii, Brachycolus spp., Brevicoryne brassicae, Calligypona marginata, Carneocephala fulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes spp.,
Chaetosiphon fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chromaphis juglandicola, Chrysomphalus ficus, Cicadulina mbila, Coccomytilus halli, Coccus spp., Cryptomyzus ribis, Dalbulus spp., Dialeurodes spp., Diaphorina spp., Diaspis spp., Doralis spp., Drosicha spp., Dysaphis spp., Dysmicoccus spp., Empoasca spp., Eriosoma spp., Erythroneura spp., Euscelis bilobatus, Geococcus cofifieae, Homalodisca coagulata, Hyalopterus arundinis, Icerya spp., Idiocerus spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp.,
Lepidosaphes spp., Lipaphis erysimi, Macrosiphum spp., Mahanarva fimbriolata,
Melanaphis sacchari, Metcalfiella spp., Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp., Nasonovia ribisnigri, Nephotettix spp., Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Parabemisia myricae, Paratrioza spp., Parlatoria spp., Pemphigus spp., Peregrinus maidis, Phenacoccus spp., Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp., Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadraspidiotus spp., Quesada gigas, Rastrococcus spp., Rhopalosiphum spp., Saissetia spp., Scaphoides titanus, Schizaphis graminum, Selenaspidus articulatus, Sogata spp., Sogatella furcifera, Sogatodes spp., Stictocephala festina,
Tenalaphara malayensis, Tinocallis caryaefoliae, Tomaspis spp., Toxoptera spp.,
Trialeurodes vaporariorum, Trioza spp., Typhlocyba spp., Unaspis spp., Viteus vitifolii.
From the order of the Hymenoptera, for example, Diprion spp., Hoplocampa spp., Lasius spp., Mono- morium pharaonis, Vespa spp..
From the order of the Isopoda, for example, Armadillidium vulgare, Oniscus asellus, Porcellio scaber.
From the order of the Isoptera, for example, Reticulitermes spp., Odontotermes spp..
From the order of the Lepidoptera, for example, Acronicta major, Aedia
leucomelas, Agrotis spp., Alabama argillacea, Anticarsia spp., Barathra brassicae,
Bucculatrix thurberiella, Bupalus piniarius, Cacoecia podana, Capua reticulana,
Carpocapsa pomonella, Cheimatobia brumata, Chilo spp., Choristoneura fumiferana, Clysia ambiguella, Cnaphalocerus spp., Earias insulana, Ephestia kuehniella, Euproctis
chrysorrhoea, Euxoa spp., Feltia spp., Galleria mellonella, Helicoverpa spp., Heliothis spp., Hofmannophila pseudospretella, Homona magnanima, Hyponomeuta padella, Laphygma spp., Lithocolletis blancardella, Lithophane antennata, Loxagrotis albicosta, Lymantria spp., Malacosoma neustria, Mamestra brassicae, Mods repanda, Mythimna separata, Oria spp., Oulema oryzae, Panolis flammea, Pectinophora gossypiella, Phyllocnistis citrella, Pieris spp., Plutella xylostella, Prodenia spp., Pseudaletia spp., Pseudoplusia includens, Pyrausta nubilalis, Spodoptera spp., Thermesia gemmatalis, Tinea pellionella, Tineola bisselliella, Tortrix viridana, Trichoplusia spp..
From the order of the Orthoptera, for example, Acheta domesticus, Blatta orientalis, Blattella germanica, Gryllotalpa spp., Leucophaea maderae, Locusta spp., Melanoplus spp., Periplaneta americana, Schistocerca gregaria.
From the order of the Siphonaptera, for example, Ceratophyllus spp., Xenopsylla cheopis.
From the order of the Symphyla, for example, Scutigerella immaculata.
From the order of the Thysanoptera, for example, Baliothrips biformis, Enneothrips flavens, Frankliniella spp., Heliothrips spp., Hercinothrips femoralis, Kakothrips spp., Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp.
From the order of the Thysanura, for example, Lepisma saccharina. The phytoparasitic nematodes include, for example, Anguina spp., Aphelenchoides spp., Belonoaimus spp., Bursaphelenchus spp., Ditylenchus dipsaci, Globodera spp., Heliocotylenchus spp., Heterodera spp., Longidorus spp., Meloidogyne spp., Pratylenchus spp., Radopholus similis, Rotylenchus spp., Trichodorus spp., Tylenchorhynchus spp., Tylenchulus spp., Tylenchulus semipenetrans, Xiphinema spp..
Furthermore, in the field of veterinary medicine, the novel compounds of the present invention can be effectively used against various harmful animal parasitic pests (endoparasites and ectoparasites), for example, insects and helminthes.
Examples of such animal parasitic pests include the pests as described below.
Examples of the insects include Gasterophilus spp., Stomoxys spp., Trichodectes spp., Rhodnius spp., Ctenocephalides canis, Cimx lecturius, Ctenocephalides felis, Lucilia cuprina, and the like.
Examples of acari include Ornithodoros spp., Ixodes spp., Boophilus spp., and the like.
In the veterinary fields, e.g. in the field of veterinary medicine, the active compounds according to the present invention are active against animal parasites, in particular ectoparasites or endoparasites.
The term endoparasites includes in particular helminths, such as cestodes, nematodes or trematodes, and protozoae, such as coccidia.
Ectoparasites are typically and preferably arthropods, in particular insects such as flies (stinging and licking), parasitic fly larvae, lice, hair lice, bird lice, fleas and the like; or acarids, such as ticks, for examples hard ticks or soft ticks, or mites, such as scab mites, harvest mites, bird mites and the like.
These parasites include:
From the order of the Anoplurida, for example Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp.; particular examples are: Linognathus setosus, Linognathus vituli, Linognathus ovillus, Linognathus oviformis, Linognathus pedalis, Linognathus stenopsis, Haematopinus asini macrocephalus, Haematopinus eurysternus, Haematopinus suis, Pediculus humanus capitis, Pediculus humanus corporis, Phylloera vastatrix, Phthirus pubis, Solenopotes capillatus; from the order of the
Mallophagida and the suborders Amblycerina and Ischnocerina, for example Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp., Felicola spp.; particular examples are: Bovicola bovis, Bovicola ovis, Bovicola limbata, Damalina bovis, Trichodectes canis, Felicola subrostratus, Bovicola caprae, Lepikentron ovis, Werneckiella equi; from the order of the Diptera and the suborders Nematocerina and Brachycerina, for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Odagmia spp., Wilhelmia spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp., Melophagus spp., Rhinoestrus spp., Tipula spp.; particular examples are: Aedes aegypti, Stegomyia albopicta (Aedes albopictus), Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis, Calliphora
erythrocephala, Chrysozona pluvialis, Culex quinquefasciatus, Culex pipiens, Culex tarsalis, Fannia canicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipula paludosa, Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomus papatasi, Phlebotomus
longipalpis, Odagmia ornata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius, Tabanus spodopterus, Tabanus atratus, Tabanus sudeticus, Hybomitra ciurea, Chrysops caecutiens, Chrysops relictus, Haematopota pluvialis, Haematopota italica, Musca autumnalis, Musca domestica, Haematobia irritans irritans, Haematobia irritans exigua, Haematobia stimulans, Hydrotaea irritans, Hydrotaea albipuncta, Chrysomya chloropyga, Chrysomya bezziana, Oestrus ovis, Hypoderma bovis, Hypoderma lineatum, Przhevalskiana silenus, Dermatobia hominis, Melophagus ovinus, Lipoptena capreoli, Lipoptena cervi, Hippobosca variegata, Hippobosca equina, Gasterophilus intestinalis, Gasterophilus haemorroidalis, Gasterophilus inermis, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus pecorum, Braula coeca; from the order of the Siphonapterida, for example Pulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.;
particular examples are: Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis; from the order of the Heteropterida, for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp..
From the order of the Blattarida, for example Blatta orientalis, Periplaneta americana, Blattela germanica, Supella spp. (e.g. Suppella longipalpa);
From the subclass of the Acari (Acarina) and the orders of the Meta- and
Mesostigmata, for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Rhipicephalus (Boophilus) spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Dermanyssus spp., Rhipicephalus spp. (the original genus of multi host ticks), Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Pneumonyssus spp.,
Sternostoma spp., Varroa spp., Acarapis spp.; particular examples are: Argas persicus, Argas reflexus, Ornithodorus moubata, Otobius megnini, Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus) calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalomma marginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus, Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes rubicundus, Ixodes scapularis, Ixodes holocyclus, Haemaphysalis concinna, Haemaphysalis punctata, Haemaphysalis cinnabarina, Haemaphysalis otophila, Haemaphysalis leachi, Haemaphysalis longicorni, Dermacentor marginatus, Dermacentor reticulatus, Dermacentor pictus, Dermacentor albipictus,
Dermacentor andersoni, Dermacentor variabilis, Hyalomma mauritanicum, Rhipicephalus sanguineus, Rhipicephalus bursa, Rhipicephalus appendiculatus, Rhipicephalus capensis, Rhipicephalus turanicus, Rhipicephalus zambeziensis, Amblyomma americanum,
Amblyomma variegatum, Amblyomma maculatum, Amblyomma hebraeum, Amblyomma cajennense, Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum, Varroa jacobsoni; from the order of the Actinedida (Prostigmata) and Acaridida (Astigmata) , for example Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp.,
Laminosioptes spp.; particular examples are: Cheyletiella yasguri, Cheyletiella blakei, Demodex canis, Demodex bovis, Demodex ovis, Demodex caprae, Demodex equi, Demodex caballi, Demodex suis, Neotrombicula autumnalis, Neotrombicula desaleri, Neoschongastia xerothermobia, Trombicula akamushi, Otodectes cynotis, Notoedres cati, Sarcoptis canis, Sarcoptes bovis, Sarcoptes ovis, Sarcoptes rupicaprae (S. caprae), Sarcoptes equi, Sarcoptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides caninum, Acarapis woodi.
The active compounds according to the invention are also suitable for controlling arthropods, helminths and protozoae, which attack animals. Animals include agricultural livestock such as, for example, cattle, sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits, chickens, turkeys, ducks, geese, cultured fish, honeybees.
Moreover, animals include domestic animals - also referred to as companion animals - such as, for example, dogs, cats, cage birds, aquarium fish and what are known as experimental animals such as, for example, hamsters, guinea pigs, rats and mice.
By controlling these arthropods, helminths and/or protozoae, it is intended to reduce deaths and improve performance (in the case of meat, milk, wool, hides, eggs, honey and the like) and health of the host animal, so that more economical and simpler animal keeping is made possible by the use of the active compounds according to the invention.
For example, it may be desirable to prevent or interrupt the uptake of blood by the parasites from the hosts.
Also, controlling the parasites may help to prevent the transmittance of infectious agents.
The term "controlling" as used herein with regard to the veterinary field, means that the active compounds are effective in reducing the incidence of the respective parasite in an animal infected with such parasites to innocuous levels.
More specifically, "controlling", as used herein, means that the active compound is effective in killing the respective parasite, inhibiting its growth, or inhibiting its proliferation. Generally, when used for the treatment of animals the active compounds according to the invention can be applied directly.
Preferably they are applied as pharmaceutical compositions which may contain pharmaceutically acceptable excipients and/or auxiliaries which are known in the art.
In the veterinary field and in animal keeping, the active compounds are applied (e.g. administered) in the known manner by enteral administration in the form of, for example, tablets, capsules, drinks, drenches, granules, pastes, boluses, the feed-through method, suppositories; by parenteral administration, such as, for example, by injections
(intramuscular, subcutaneous, intravenous, intraperitoneal and the like), implants, by nasal application, by dermal application in the form of, for example, bathing or dipping, spraying, pouring-on and spotting-on, washing, dusting, and with the aid of active-compound- comprising shaped articles such as collars, ear tags, tail tags, limb bands, halters, marking devices and the like. The active compounds may be formulated as shampoo or as suitable formulations usable in aerosols, unpressurized sprays, for example pump sprays and atomizer sprays.
When used for livestock, poultry, domestic animals and the like, the active compounds according to the invention can be applied as formulations (for example powders, wettable powders ["WP"], emulsions, emulsifiable concentrates ["EC"], flowables, homogeneous solutions, and suspension concentrates ["SC"]) which comprise the active compounds in an amount of from 1 to 80 percent by weight, either directly or after dilution (e.g. 100- to 10 000-fold dilution), or else as a chemical bath.
When used in the veterinary field the active compounds according to the invention may be used in combination with suitable synergists or other active compounds, such as for example, acaricides, insecticides, anthelmintics, anti-protozoal drugs.
In the present invention, a substance having an insecticidal action against pests including all of these is referred to as an insecticide.
An active compound of the present invention can be prepared in conventional formulation forms, when used as an insecticide.
Examples of the formulation forms include solutions, emulsions, wettable powders, water dispersible granules, suspensions, powders, foams, pastes, tablets, granules, aerosols, active compound-infiltrated natural and synthetic materials, microcapsules, seed coating agents, formulations used with a combustion apparatus (for example, fumigation and smoking cartridges, cans, coils or the like as the combustion apparatus), ULV (cold mist, warm mist), and the like.
These formulations can be produced by methods that are known per se.
For example, a formulation can be produced by mixing the active compound with a developer, that is, a liquid diluent or carrier; a liquefied gas diluent or carrier; a solid diluent or carrier, and optionally with a surfactant, that is, an emulsifier and/or dispersant and/or foaming agent.
In the case where water is used as the developer, for example, an organic solvent can also be used as an auxiliary solvent.
Examples of the liquid diluent or carrier include aromatic hydrocarbons (for example, xylene, toluene, alkylnaphthalene and the like), chlorinated aromatic or chlorinated aliphatic hydrocarbons (for example, chlorobenzenes, ethylene chlorides, methylene chlorides), aliphatic hydrocarbons (for example, cyclohexanes), paraffins (for example, mineral oil fractions), alcohols (for example, butanol, glycols and their ethers, esters and the like), ketones (for example, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and the like), strongly polar solvents (for example, dimethylformamide, dimethylsulfoxide and the like), water and the like. The liquefied gas diluent or carrier may be those which are gaseous at normal temperature and normal pressure, for example, aerosol propellants such as butane, propane, nitrogen gas, carbon dioxide and halogenated hydrocarbons. Examples of the solid diluent include pulverized natural minerals (for example, kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite, diatomaceous earth, and the like), pulverized synthetic minerals (for example, highly dispersed silicic acid, alumina, silicates and the like), and the like. Examples of the solid carrier for granules include pulverized and screened rocks (for example, calcite, marble, pumice, sepiolite, dolomite and the like), synthetic granules of inorganic and organic powder, fine particles of organic materials (for example, sawdust, coconut shells, maize cobs, tobacco stalk and the like), and the like. Examples of the emulsifier and/or foaming agent include nonionic and anionic emulsifiers [for example, polyoxyethylene fatty acid esters, polyoxyethylene fatty acid alcohol ethers (for example, alkylaryl polyglycol ether), alkylsulfonates, alkylsulfates, arylsulfonates and the like], albumin hydro lyzate, and the like. Examples of the dispersant include lignin sulfite waste liquor and methylcellulose.
Fixing agents can also be used in the formulations (powders, granules, emulsions), and examples of the fixing agent include carboxymethylcellulose, natural and synthetic polymers (for example, gum arabic, polyvinyl alcohol, polyvinyl acetate, and the like) and the like. Colorants can also be used, and examples of the colorants include inorganic pigments (for example, iron oxide, titanium oxide, Prussian Blue and the like), organic dyes such as alizarin dyes, azo dyes or metal phthalocyanine dyes, and in addition, trace elements such as the salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc. The formulations in general can contain the active ingredient in an amount ranging from 0.1 to 95 percent by weight, and preferably 0.5 to 90 percent> by weight. The compound according to the present invention can also exist as an admixture with other active compounds, for example, insecticides, poisonous baits, bactericides, miticides, nematicides, fungicides, growth regulators, herbicides and the like, in the form of their commercially useful formulation forms and in the application forms prepared from those formulations.
The content of the compound according to the present invention in a commercially useful application form can be varied within a wide range. The concentration of the active compound according to the present invention in actual usage can be, for example, in the range of 0.0000001 to 100 percent by weight, and preferably 0.00001 to 1 percent by weight.
The compounds according to the present invention can be used through
conventional methods that are appropriate for the usage form.
The active compound of the present invention have, when used against hygiene pests and pests associated with stored products, stability effective against alkali on lime materials, and also shows excellent residual effectiveness on wood and soil. The compounds of the invention may have favourable properties with respect to amount appled, residue formulation, selectivity, toxicity, production methodology, high activity, wide spectrum of control, safety, control of resistant organisms, e.g. pests that are resistant to organic phosphorus agents and/or carbamate agents.
Further embodiments of the invention are described below.
The compounds of formula (I*) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests. The pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fiber products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
The compounds of the invention may be used for example on turf, ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens, for example conifers, as well as for tree injection, pest management and the like.
The compounds of the invention may be used to control animal housing pests including: Ants, Bedbugs (adult), Bees, Beetles, Boxelder Bugs, Carpenter Bees, Carpet Beetles, Centipedes, Cigarette, Beetles, Clover Mites, Cockroaches, Confused Flour Beetle, Crickets, Earwigs, Firebrats, Fleas, Flies, Lesser Grain Borers, Millipedes, Mosquitoes, Red Flour Beetles, Rice Weevils, Saw-toothed Grain Beetles, Silverfish, Sowbugs, Spiders, Termites, Ticks, Wasps, Cockroaches, Crickets, Flies, Litter Beetles (such as Darkling, Hide, and Carrion), Mosquitoes, Pillbugs, Scorpions, Spiders, Spider Mites (Twospotted, Spruce), Ticks.
The compounds of the invention may be used to control ornamental pests including: Ants (Including Imported fire ants), Armyworms, Azalea caterpillars, Aphids, Bagworms, Black vine weevils (adult), Boxelder bugs, Budworms, California oakworms, Cankerworms, Cockroaches, Crickets, Cutworms, Eastern tent caterpillars, Elm leaf beetles, European sawflies, Fall webworms, Flea beetles, Forest tent caterpillars, Gypsy moth larvae, Japanese beetles (adults), June beetles (adults), Lace bugs, Leaf-feeding caterpillars, Leafhoppers, Leafminers (adults), Leaf rollers, Leaf skeletonizers, Midges, Mosquitoes, Oleander moth larvae, Pillbugs, Pine sawflies, Pine shoot beetles, Pinetip moths, Plant bugs, Root weevils, Sawflies, Scale insects (crawlers), Spiders, Spittlebugs, Striped beetles, Striped oakworms, Thrips, Tip moths, Tussock moth larvae, Wasps, Broadmites, Brown softscales, California redscales (crawlers), Clover mites, Mealybugs, Pineneedlescales (crawlers), Spider mites, Whiteflies
The compounds of the invention may be used to control turf pests including: Ants
(Including Imported fire ants, Armyworms, Centipedes, Crickets, Cutworms, Earwigs, Fleas (adult), Grasshoppers, Japanese beetles (adult), Millipedes, Mites, Mosquitoes (adult), Pillbugs, Sod webworms, Sow bugs, Ticks (including species which transmit Lyme disease), Bluegrass billbugs (adult), Black turfgrass ataenius (adult), Chiggers, Fleas (adult), Grubs (suppression), Hyperodes weevils (adult), Mole crickets (nymphs and young adults), Mole Crickets (mature adults), Chinch Bugs
Examples of pest species which may be controlled by the compounds of formula (I*) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.
(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa
decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (white flies), Bemisia tabaci (white fly), Ostrinia nubilalis (European corn borer), Spodoptera littoralis (cotton leafworm), Heliothis virescens (tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pieris brassicae (white butterfly), Plutella xylostella (diamond back moth), Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta migratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp. (rootworms), Panonychus ulmi (European red mite), Panonychus citri (citrus red mite), Tetranychus urticae (two-spotted spider mite), Tetranychus cinnabarinus (carmine spider mite),
Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpus spp. (fiat mites), Boophilus microplus (cattle tick), Dermacentor variabilis (American dog tick), Ctenocephalides felis (cat flea), Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti (mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes), Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplaneta americana (cockroach), Blatta orientalis (cockroach), termites of the Mastotermitidae (for example Mastotermes spp.), the Kalotermitidae (for example Neotermes spp.), the
Rhinotermitidae (for example Coptotermes formosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R. hesperus, and R. santonensis) and the Termitidae (for example Globitermes sulfureus), Solenopsis geminata (fire ant), Monomorium pharaonis (pharaoh's ant),
Damalinia spp. and Linognathus spp. (biting and sucking lice), Meloidogyne spp. (root knot nematodes), Globodera spp. and Heterodera spp. (cyst nematodes), Pratylenchus spp.
(lesion nematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulus spp. (citrus nematodes), Haemonchus contortus (barber pole worm), Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastro intestinal nematodes) and Deroceras reticulatum (slug).
The compounds of the invention may be used for pest control on various plants, including soybean (e.g. in some cases 10-70g/ha), corn (e.g. in some cases 10-70g/ha), sugarcane (e.g. in some cases 20-200g/ha), alfalfa (e.g. in some cases 10-70g/ha), brassicas (e.g. in some cases 10-50g/ha), oilseed rape (e.g. canola) (e.g. in some cases 20-70g/ha), potatoes (including sweet potatoes) (e.g. in some cases 10-70g/ha), cotton (e.g. in some cases 10-70g/ha), rice (e.g. in some cases 10-70g/ha), coffee (e.g. in some cases 30-150g/ha), citrus (e.g. in some cases 60-200g/ha), almonds (e.g. in some cases 40-180g/ha), fruiting vegetables (e.g. tomatoes, pepper, chili, eggplant, cucumber, squash etc.) (e.g. in some cases 10-80g/ha), tea (e.g. in some cases 20-150g/ha), bulb vegetables (e.g. onion, leek etc.) (e.g. in some cases 30-90g/ha), grapes (e.g. in some cases 30-180g/ha), pome fruit (e.g. apples, pears etc.) (e.g. in some cases 30-180g/ha), and stone fruit (e.g. pears, plums etc.) (e.g. in some cases 30-180g/ha).
The compounds of the invention may be used on soybean to control, for example, Elasmopalpus lignosellus, Diloboderus abderus, Diabrotica speciosa, Sternechus subsignatus, Formicidae, Agrotis ypsilon, Julus ssp., Anticarsia gemmatalis, Megascelis ssp., Procornitermes ssp., Gryllotalpidae, Nezara viridula, Piezodorus spp. , Acrosternum spp., Neomegalotomus spp., Cerotoma trifurcata, Popillia japonica, Edessa spp., Liogenys fuscus, Euchistus heros, stalk borer, Scaptocoris castanea, phyllophaga spp., Pseudoplusia includens, Spodoptera spp., Bemisia tabaci, Agriotes spp. The compounds of the invention are preferably used on soybean to control Diloboderus abderus, Diabrotica speciosa, Nezara viridula, Piezodorus spp. , Acrosternum spp., Cerotoma trifurcata, Popillia japonica, Euchistus heros, Phyllophaga spp., Agriotes spp..
The compounds of the invention may be used on corn to control, for example, Euchistus heros, Dichelops furcatus, Diloboderus abderus, Elasmopalpus lignosellus, Spodoptera frugiperda, Nezara viridula, Cerotoma trifurcata, Popillia japonica, Agrotis ypsilon, Diabrotica speciosa, Heteroptera, Procornitermes ssp., Scaptocoris castanea, Formicidae, Julus ssp., Dalbulus maidis, Diabrotica virgifera, Mods latipes, Bemisia tabaci, heliothis spp., Tetranychus spp., Thrips spp., phyllophaga spp., scaptocoris spp., Liogenys fuscus, Spodoptera spp., Ostrinia spp., Sesamia spp., Agriotes spp.. The compounds of the invention are preferably used on corn to control Euchistus heros, Dichelops furcatus, Diloboderus abderus, Nezara viridula, Cerotoma trifurcata, Popillia japonica, Diabrotica speciosa, Diabrotica virgifera, Tetranychus spp., Thrips spp., Phyllophaga spp., Scaptocoris spp., Agriotes spp..
The compounds of the invention may be used on sugar cane to control, for example,
Sphenophorus spp., termites, Mahanarva spp.. The compounds of the invention are preferably used on sugar cane to control termites, Mahanarva spp..
The compounds of the invention may be used on alfalfa to control, for example, Hypera brunneipennis, Hypera postica, Colias eurytheme, Collops spp., Empoasca solana, Epitrix, Geocoris spp., Lygus hesperus, Lygus lineolaris, Spissistilus spp, Spodoptera spp., Trichoplusia ni. The compounds of the invention are preferably used on alfalfa to control Hypera brunneipennis, Hypera postica, Empoasca solana, Epitrix, Lygus hesperus, Lygus lineolaris, Trichoplusia ni.
The compounds of the invention may be used on brassicas to control, for example, Plutella xylostella, Pieris spp., Mamestra spp., Plusia spp., Trichoplusia ni, Phyllotreta spp., Spodoptera spp., Empoasca solana, Thrips spp., Spodoptera spp., Delia spp.. The
compounds of the invention are preferably used on brassicas to control Plutella xylostella Pieris spp., Plusia spp., Trichoplusia ni, Phyllotreta spp., Thrips spp.. The compounds of the invention may be used on oil seed rape, e.g. canola, to control, for example, Meligethes spp., Ceutorhynchus napi, Psylloides spp.
The compounds of the invention may be used on potatoes, including sweet potatoes, to control, for example, Empoasca spp., Leptinotarsa spp., Diabrotica speciosa,
Phthorimaea spp., Paratrioza spp., Maladera matrida, Agriotes spp. The compounds of the invention are preferably used on potatoes, including sweet potatoes, to control Empoasca spp., Leptinotarsa spp., Diabrotica speciosa, Phthorimaea spp., Paratrioza spp., Agriotes spp.
The compounds of the invention may be used on cotton to control, for example, Anthonomus grandis, Pectinophora spp., Heliothis spp., Spodoptera spp., Tetranychus spp., Empoasca spp., Thrips spp., Bemisia tabaci, Lygus spp., Phyllophaga spp., Scaptocoris spp. The compounds of the invention are preferably used on cotton to control Anthonomus grandis, Tetranychus spp., Empoasca spp., Thrips spp., Lygus spp., phyllophaga spp., Scaptocoris spp.
The compounds of the invention may be used on rice to control, for example,
Leptocorisa spp., Cnaphalocrosis spp., Chilo spp., Scirpophaga spp., Lissorhoptrus spp., Oebalus pugnax. The compounds of the invention are preferably used on rice to control Leptocorisa spp., Lissorhoptrus spp., Oebalus pugnax.
The compounds of the invention may be used on coffee to control, for example, Hypothenemus Hampei, Perileucoptera Coffeella, Tetranychus spp. The compounds of the invention are preferably used on coffee to control Hypothenemus Hampei, Perileucoptera coffeella.
The compounds of the invention may be used on citrus to control, for example, Panonychus citri, Phyllocoptruta oleivora, Brevipalpus spp., Diaphorina citri, Scirtothrips spp., Thrips spp., Unaspis spp., Ceratitis capitata, Phyllocnistis spp. The compounds of the invention are preferably used on citrus to control Panonychus citri, Phyllocoptruta oleivora, Brevipalpus spp., Diaphorina citri, Scirtothrips spp., Thrips spp., Phyllocnistis spp..
The compounds of the invention may be used on almonds to control, for example, Amyelois transitella, Tetranychus spp..
The compounds of the invention may be used on fruiting vegetable, including tomatoes, pepper, chili, eggplant, cucumber, squash etc, to control Thrips spp., Tetranychus spp., Polyphagotarsonemus spp., Aculops spp., Empoasca spp., Spodoptera spp., Heliothis spp., Tuta absoluta, Liriomyza spp., Bemisia tabaci, Trialeurodes spp., Paratrioza spp., Frankliniella occidentalis, Frankliniella spp., Anthonomus spp., Phyllotreta spp., Amrasca spp., Epilachna spp., Halyomorpha spp., Scirtothrips spp., Leucinodes spp., Neoleucinodes spp.. The compounds of the invention are preferably used on fruiting vegetable, including tomatoes, pepper, chili, eggplant, cucumber, squash etc, to control, for example, Thrips spp., Tetranychus spp., Polyphagotarsonemus spp., Aculops spp., Empoasca spp., Spodoptera spp., Heliothis spp., Zwto absoluta, Liriomyza spp., Paratrioza spp., Frankliniella occidentalis, Frankliniella spp., Amrasca spp., Scirtothrips spp., Leucinodes spp.,
Neoleucinodes spp..
The compounds of the invention may be used on tea to control, for example, Pseudaulacaspis spp., Empoasca spp., Scirtothrips spp., Caloptilia theivora. The compounds of the invention are prefrerably used on tea to control Empoasca spp., Scirtothrips spp.
The compounds of the invention may be used on bulb vegetables, including onion, leek etc to control, for example, Thrips spp., Spodoptera spp., Heliothis spp.. The compounds of the invention are preferably used on bulb vegetables, including onion, leek etc to control Thrips spp..
The compounds of the invention may be used on grapes to control, for example, Empoasca spp., Lobesia spp., Frankliniella spp., Thrips spp., Tetranychus spp.,
Rhipiphorothrips Cruentatus, Eotetranychus Willamettei, Erythroneura Elegantula,
Scaphoides spp.. The compounds of the invention are preferably used on grapes to control Frankliniella spp., Thrips spp., Tetranychus spp., Rhipiphorothrips Cruentatus, Scaphoides spp..
The compounds of the invention may be used on pome fruit, including apples, pairs etc, to control, for example, Cacopsylla spp., Psylla spp., Panonychus ulmi, Cydia pomonella. The compounds of the invention are preferably used on pome fruit, including apples, pairs etc, to control Cacopsylla spp., Psylla spp., Panonychus ulmi.
The compounds of the invention may be used on stone fruit to control, for example, Grapholita molesta, Scirtothrips spp., Thrips spp., Frankliniella spp., Tetranychus spp. The compounds of the invention are preferably used on stone fruit to control Scirtothrips spp., Thrips spp., Frankliniella spp., Tetranychus spp..The invention therefore provides a method of combating and/or controlling an animal pest, e.g. an invertebrate animal pest, which comprises applying to the pest, to a locus of the pest, or to a plant susceptible to attack by the pest a pesticidally effective amount of a compound of formula (I*). In particular, the invention provides a method of combating and/or controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or moUuscicidally effective amount of a compound of formula (I*), or a composition containing a compound of formula (I*), to a pest, a locus of pest, preferably a plant, or to a plant susceptible to attack by a pest, The compounds of formula (I*) are preferably used against insects, acarines or nematodes.
The term "plant" as used herein includes seedlings, bushes and trees. Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO- and HPPD -inhibitors) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is
Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and
LibertyLink®.
Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavor).
In order to apply a compound of formula (I*) as an insecticide, acaricide, nematicide or molluscicide to a pest, a locus of pest, or to a plant susceptible to attack by a pest, a compound of formula (I*) is usually formulated into a composition which includes, in addition to the compound of formula (I*), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (I*). The composition is generally used for the control of pests such that a compound of formula (I*) is applied at a rate of from 0. lg to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
When used in a seed dressing, a compound of formula (I*) is generally used at a rate of 0.000 lg to lOg (for example 0.00 lg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
In another aspect the present invention provides a composition comprising a pesticidally effective amount of a compound of formula (I*), in particular an insecticidal, acaricidal, nematicidal or molluscicidal composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I*) and a suitable carrier or diluent therefor. The composition is preferably an insecticidal, acaricidal, nematicidal or molluscicidal composition.
The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (I*).
Dustable powders (DP) may be prepared by mixing a compound of formula (I*) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulfur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
Soluble powders (SP) may be prepared by mixing a compound of formula (I*) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).
Wettable powders (WP) may be prepared by mixing a compound of formula (I*) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound of formula (I*) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I*) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (I*) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulfates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (I*) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallization in a spray tank).
Emulsifiable concentrates (EC) or oil-in- water emulsions (EW) may be prepared by dissolving a compound of formula (I*) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or
methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N- alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as Cs-Cio fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (I*) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (I*) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I*). SCs may be prepared by ball or bead milling the solid compound of formula (I*) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle.
Alternatively, a compound of formula (I*) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
Aerosol formulations comprise a compound of formula (I*) and a suitable propellant (for example n-butane). A compound of formula (I*) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n- propanol) to provide compositions for use in non-pressurized, hand-actuated spray pumps.
A compound of formula (I*) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound. Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerization stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I*) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula (I*) and they may be used for seed treatment. A compound of formula (I*) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (I*)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (I*)).
A compound of formula (I*) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film- forming barrier).
Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (for example sodium lauryl sulfate), salts of sulfonated aromatic compounds (for example sodium dodecylbenzenesulfonate, calcium
dodecylbenzenesulfonate, butylnaphthalene sulfonate and mixtures of sodium di- z'sopropyl- and tri-z'sopropyl-naphthalene sulfonates), ether sulfates, alcohol ether sulfates (for example sodium laureth-3-sulfate), ether carboxylates (for example sodium laureth-3- carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide
(predominately di-esters), for example the reaction between lauryl alcohol and
tetraphosphoric acid; additionally these products may be ethoxylated), sulfosuccinamates, paraffin or olefine sulfonates, taurates and lignosulfonates.
Suitable SFAs of the amphoteric type include betaines, propionates and glycinates. Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
A compound of formula (I*) may be applied by any of the known means of applying pesticidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapor or applied through distribution or
incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
A compound of formula (I*) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (I*) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.
A compound of formula (I*) may be used in mixtures with fertilizers (for example nitrogen-, potassium- or phosphorus-containing fertilizers). Suitable formulation types include granules of fertilizer. The mixtures preferably contain up to 25% by weight of the compound of formula (I*).
The invention therefore also provides a fertilizer composition comprising a fertilizer and a compound of formula (I*).
The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
The compound of formula (I*) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, e.g. a insecticide, fungicide or herbicide, or a synergist or plant growth regulator where appropriate. An additional active ingredient may provide a composition having a broader spectrum of activity or increased persistence at a locus; synergize the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I*); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition.
The compounds of the invention are also useful in the field of animal health, e.g. they may be used against parasitic invertebrate pests, more preferably against parasitic invertebrate pests in or on an animal. Examples of pests include nematodes, trematodes, cestodes, flies, mites, tricks, lice, fleas, true bugs and maggots. The animal may be a non- human animal, e.g. an animal associated with agriculture, e.g. a cow, a pig, a sheep, a goat, a horse, or a donkey, or a companion animal, e.g. a dog or a cat.
In a further aspect the invention provides a compound of the invention for use in a method of therapeutic treatment. In a further aspect the invention relates to a method of controlling parasitic invertebrate pests in or on an animal comprising administering a pesticidally effective amount of a compound of the invention. The administration may be for example oral administration, parenteral administration or external administration, e.g. to the surface of the animal body. In a further aspect the invention relates to a compound of the invention for controlling parasitic invertebrate pests in or on an animal. In a further aspect the invention relates to use of a compound of the invention in the manufacture of a medicament for controlling parasitic invertebrate pests in or on an animal
In a further aspect, the invention relates to a method of controlling parasitic invertebrate pests comprising administering a pesticidally effective amount of a compound of the invention to the environment in which an animal resides.
In a further aspect the invention relates to a method of protecting an animal from a parasitic invertebrate pest comprising administering to the animal a pesticidally effective amount of a compound of the invention. In a further aspect the invention relates to a compound of the invention for use in protecting an animal from a parasitic invertebrate pest. In a further aspect the invention relates to use of a compound of the invention in the manufacture of a medicament for protecting an animal from a parasitic invertebrate pest.
In a further aspect the invention provides a method of treating an animal suffering from a parasitic invertebrate pest comprising administering to the animal a pesticidally effective amount of a compound of the invention. In a further aspect the invention relates to a compound of the invention for use in treating an animal suffering from a parasitic invertebrate pest. In a further aspect the invention relates to use of a compound of the invention in the manufacture of a medicament for treating an animal suffering from a parasitic invertebrate pest.
In a further aspect, the invention provides a pharmaceutical composition comprising a compound of the invention and a pharmaceutically suitable excipient.
The compounds of the invention may be used alone or in combination with one or more other biologically active ingredients.
In one aspect the invention provides a combination product comprising a pesticidally effective amount of a component A and a pesticidally effective amount of component B wherein component A is a compound of the invention and component B is a compound as described below. The compounds of the invention may be used in combination with anthelmintic agents. Such anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP- 357460, EP -444964 and EP-594291. Additional anthelmintic agents include
semisynthetic and biosynthetic avermectin/milbemycin derivatives such as those described in US-5015630, WO-9415944 and WO-9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole,
mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel. Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
The compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in US-5478855, US- 4639771 and DE- 19520936.
The compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO- 9615121 and also with anthelmintic active cyclic depsipeptides such as those described in WO-9611945, WO-9319053, WO- 9325543, EP-626375, EP-382173, WO-9419334, EP- 382173, and EP-503538.
The compounds of the invention may be used in combination with other
ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like;
neonicotinoids such as imidacloprid and the like.
The compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers W095/19363 or WO04/72086, particularly the compounds disclosed therein.
Other examples of such biologically active compounds that the compounds of the invention may be used in combination with include but are not restricted to the following:
Organophosphates: acephate, azamethiphos, azinphos-ethyl, azinphos- methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, methacriphos, methamidophos, methidathion, methyl- parathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, paraoxon, parathion, parathion-methyl, phenthoate, phosalone, phosfolan, phosphocarb, phosmet, phosphamidon, phorate, phoxim, pirimiphos, pirimiphos- methyl, profenofos, propaphos, proetamphos, prothiofos, pyraclofos,
pyridapenthion, quinalphos, sulprophos, temephos, terbufos, tebupirimfos, tetrachlorvinphos, thimeton, triazophos, trichlorfon, vamidothion.
Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb, HCN-801, isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m- cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
Pyrethroids: acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E) - (1 R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, bifenthrin, beta -cyfluthrin, cyfluthrin, a-cypermethrin, beta -cypermethrin, bioallethrin, bioallethrin((S)-cyclopentylisomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, ethofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D isomer), imiprothrin, cyhalothrin, lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins (natural products), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluofen, t- fluvalinate, tefluthrin, tralomethrin, Zeta-cypermethrin.
Arthropod growth regulators: a) chitin synthesis inhibitors: benzoylureas:
chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene),
fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-118, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG- 505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine, diacloden, diafenthiuron, DBI-3204, dinactin, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI- 800, fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox, fluproxyfen, halofenprox, hydramethylnon, IKI-220, kanemite, NC- 196, neem guard, nidinorterfuran, nitenpyram, SD-35651 , WL- 108477, pirydaryl, propargite, protrifenbute, pymethrozine, pyridaben, pyrimidifen, NC-1111, R- 195,RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301.
Fungicides: acibenzolar, aldimorph, ampropylfos, andoprim, azaconazole, azoxystrobin, benalaxyl, benomyl, bialaphos, blasticidin-S, Bordeaux mixture,
bromuconazole, bupirimate, carpropamid, captafol, captan, carbendazim, chlorfenazole, chloroneb, chloropicrin, chlorothalonil, chlozolinate, copper oxychloride, copper salts, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, cyprofuram, RH-7281, diclocymet, diclobutrazole, diclomezine, dicloran, difenoconazole, RP-407213, dimethomorph, domoxystrobin, diniconazole, diniconazole-M, dodine, edifenphos, epoxiconazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramid, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fluazinam, fludioxonil, flumetover, flumorf/flumorlin, fentin hydroxide, fluoxastrobin, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl- aluminium, furalaxyl, furametapyr, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, krsoxim-methyl, mancozeb, maneb, mefenoxam, mepronil, metalaxyl, metconazole, metominostrobin/fenominostrobin, metrafenone, myclobutanil, neo- asozin, nicobifen, orysastrobin, oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propamocarb, propioconazole, proquinazid, prothioconazole, pyrifenox, pyraclostrobin, pyrimethanil, pyroquilon, quinoxyfen, spiroxamine, sulfur, tebuconazole, tetrconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, triadimefon, triadimenol, tricyclazole, trifloxystrobin, triticonazole, validamycin, vinclozin.
Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus
thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
Bactericides: chlortetracycline, oxytetracycline, streptomycin.
Other biological agents: enrofloxacin, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, carprofen,
metaflumizone, praziquarantel, triclabendazole.
When used in combination with other active ingredients, the compounds of the invention are preferably used in combination with the following (where "TX means a specific compound or a group of compounds as defined above): imidacloprid + TX, enrofloxacin + TX, praziquantel + TX, pyrantel embonate + TX, febantel + TX, penethamate + TX, moloxicam + TX, cefalexin + TX, kanamycin + TX, pimobendan + TX, clenbuterol + TX, fipronil + TX, ivermectin + TX, omeprazole + TX, tiamulin + TX, benazepril + TX, milbemycin + TX, cyromazine + TX, thiamethoxam + TX, pyriprole + TX, deltamethrin + TX, cefquinome + TX, florfenicol + TX, buserelin + TX, cefovecin + TX, tulathromycin + TX, ceftiour + TX, selamectin + TX, carprofen + TX, metaflumizone + TX, moxidectin + TX, methoprene (including S-methoprene) + TX, clorsulon + TX, pyrantel + TX, amitraz + TX, triclabendazole + TX, avermectin + TX, abamectin + TX, emamectin + TX,
eprinomectin + TX, doramectin + TX, selamectin + TX, nemadectin + TX, albendazole + TX, cambendazole + TX, fenbendazole + TX, flubendazole + TX, mebendazole + TX, oxfendazole + TX, oxibendazole + TX, parbendazole + TX, tetramisole + TX, levamisole + TX, pyrantel pamoate + TX, oxantel + TX, morantel + TX, triclabendazole + TX, epsiprantel + TX, fipronil + TX, lufenuron + TX, ecdysone + TX or tebufenozide + TX; more preferably, enrofloxacin + TX, praziquantel + TX, pyrantel embonate + TX, febantel + TX, penethamate + TX, moloxicam + TX, cefalexin + TX, kanamycin + TX, pimobendan + TX, clenbuterol + TX, omeprazole + TX, tiamulin + TX, benazepril + TX, pyriprole + TX, cefquinome + TX, florfenicol + TX, buserelin + TX, cefovecin + TX, tulathromycin + TX, ceftiour + TX, selamectin + TX, carprofen + TX, moxidectin + TX, clorsulon + TX, pyrantel + TX, eprinomectin + TX, doramectin + TX, selamectin + TX, nemadectin + TX, albendazole + TX, cambendazole + TX, fenbendazole + TX, flubendazole + TX,
mebendazole + TX, oxfendazole + TX, oxibendazole + TX, parbendazole + TX, tetramisole + TX, levamisole + TX, pyrantel pamoate + TX, oxantel + TX, morantel + TX,
triclabendazole + TX, epsiprantel + TX, lufenuron + TX or ecdysone + TX; even more preferably enrofloxacin + TX, praziquantel + TX, pyrantel embonate + TX, febantel + TX, penethamate + TX, moloxicam + TX, cefalexin + TX, kanamycin + TX, pimobendan + TX, clenbuterol + TX, omeprazole + TX, tiamulin + TX, benazepril + TX, pyriprole + TX, cefquinome + TX, florfenicol + TX, buserelin + TX, cefovecin + TX, tulathromycin + TX, ceftiour + TX, selamectin + TX, carprofen + TX, moxidectin + TX, clorsulon + TX or pyrantel + TX.
Examples of ratios include 100: 1 to 1 :6000, 50:1 to 1 :50, 20: 1 to 1 :20, even more especially from 10: 1 to 1 : 10, 5: 1 to 1 :5, 2: 1 to 1 :2, 4: 1 to 2: 1, 1 :1, or 5:1, or 5:2, or 5:3, or 5:4, or 4: 1, or 4:2, or 4:3, or 3: 1, or 3:2, or 2: 1, or 1 :5, or 2:5, or 3:5, or 4:5, or 1 :4, or 2:4, or 3:4, or 1 :3, or 2:3, or 1 :2, or 1 :600, or 1 :300, or 1 : 150, or 1 :35, or 2:35, or 4:35, or 1 :75, or 2:75, or 4:75, or 1 :6000, or 1 :3000, or 1 : 1500, or 1 :350, or 2:350, or 4:350, or 1 :750, or 2:750, or 4:750. Those mixing ratios are understood to include, on the one hand, ratios by weight and also, on other hand, molar ratios.
Of particular note is a combination where the additional active ingredient has a different site of action from the compound of formula I. In certain instances, a combination with at least one other parasitic invertebrate pest control active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a combination product of the invention may comprise a pesticidally effective amount of a compound of formula I and pesticidally effective amount of at least one additional parasitic invertebrate pest control active ingredient having a similar spectrum of control but a different site of action.
One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding non salt forms, salts share the biological utility of the non salt forms.
Thus a wide variety of salts of compounds of the invention (and active ingredients used in combination with the active ingredients of the invention) may be useful for control of invertebrate pests and animal parasites. Salts include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. The compounds of the invention also include N-oxides. Accordingly, the invention comprises combinations of compounds of the invention including N-oxides and salts thereof and an additional active ingredient including N-oxides and salts thereof.
The compositions for use in animal health may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT
Publication WO2003024222.
The compounds of the invention can be applied without other adjuvants, but most often application will be of a formulation comprising one or more active ingredients with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. One method of application involves spraying a water dispersion or refined oil solution of the combination products. Compositions with spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance compound efficacy. Such sprays can be applied from spray containers such as a can, a bottle or other container, either by means of a pump or by releasing it from a pressurized container, e.g., a pressurized aerosol spray can. Such spray compositions can take various forms, for example, sprays, mists, foams, fumes or fog. Such spray compositions thus can further comprise propellants, foaming agents, etc. as the case may be. Of note is a spray composition comprising a pesticidally effective amount of a compound of the invention and a carrier. One embodiment of such a spray composition comprises a pesticidally effective amount of a compound of the invention and a propellant. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Of note is a spray composition (and a method utilizing such a spray composition dispensed from a spray container) used to control at least one parasitic invertebrate pest selected from the group consisting of mosquitoes, black flies, stable flies, deer flies, horse flies, wasps, yellow jackets, hornets, ticks, spiders, ants, gnats, and the like, including individually or in combinations.
The controlling of animal parasites includes controlling external parasites that are parasitic to the surface of the body of the host animal (e.g., shoulders, armpits, abdomen, inner part of the thighs) and internal parasites that are parasitic to the inside of the body of the host animal (e.g., stomach, intestine, lung, veins, under the skin, lymphatic tissue).
External parasitic or disease transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites and fleas. Internal parasites include heartworms, hookworms and helminths. The compounds of the invention may be particularly suitable for combating external parasitic pests. The compounds of the invention may be suitable for systemic and/or non-systemic control of infestation or infection by parasites on animals.
The compounds of the invention may be suitable for combating parasitic
invertebrate pests that infest animal subjects including those in the wild, livestock and agricultural working animals. Livestock is the term used to refer (singularly or plurally) to a domesticated animal intentionally reared in an agricultural setting to make produce such as food or fiber, or for its labor; examples of livestock include cattle, sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, hens, turkeys, ducks and geese (e.g., raised for meat, milk, butter, eggs, fur, leather, feathers and/or wool). By combating parasites, fatalities and performance reduction (in terms of meat, milk, wool, skins, eggs, etc.) are reduced, so that applying the compounds of the invention allows more economic and simple husbandry of animals.
The compounds of the invention may be suitable for combating parasitic
invertebrate pests that infest companion animals and pets (e.g., dogs, cats, pet birds and aquarium fish), research and experimental animals (e.g., hamsters, guinea pigs, rats and mice), as well as animals raised for/in zoos, wild habitats and/or circuses.
In an embodiment of this invention, the animal is preferably a vertebrate, and more preferably a mammal, avian or fish. In a particular embodiment, the animal subject is a mammal (including great apes, such as humans). Other mammalian subjects include primates (e.g., monkeys), bovine (e.g., cattle or dairy cows), porcine (e.g., hogs or pigs), ovine (e.g., goats or sheep), equine (e.g., horses), canine (e.g., dogs), feline (e.g., house cats), camels, deer, donkeys, buffalos, antelopes, rabbits, and rodents (e.g., guinea pigs, squirrels, rats, mice, gerbils, and hamsters). Avians include Anatidae (swans, ducks and geese), Columbidae (e.g., doves and pigeons), Phasianidae (e.g., partridges, grouse and turkeys), Thesienidae (e.g., domestic chickens), Psittacines (e.g., parakeets, macaws, and parrots), game birds, and ratites (e.g., ostriches).
Birds treated or protected by the compounds of the invention can be associated with either commercial or noncommercial aviculture. These include Anatidae, such as swans, geese, and ducks, Columbidae, such as doves and domestic pigeons, Phasianidae, such as partridge, grouse and turkeys, Thesienidae, such as domestic chickens, and Psittacines, such as parakeets, macaws and parrots raised for the pet or collector market, among others.
For purposes of the present invention, the term "fish" is understood to include without limitation, the Teleosti grouping of fish, i.e., teleosts. Both the Salmoniformes order (which includes the Salmonidae family) and the Perciformes order (which includes the Centrarchidae family) are contained within the Teleosti grouping. Examples of potential fish recipients include the Salmonidae, Serranidae, Sparidae, Cichlidae, and Centrarchidae, among others.
Other animals are also contemplated to benefit from the inventive methods, including marsupials (such as kangaroos), reptiles (such as farmed turtles), and other economically important domestic animals for which the inventive methods are safe and effective in treating or preventing parasite infection or infestation.
Examples of parasitic invertebrate pests controlled by administering a pesticidally effective amount of the compounds of the invention to an animal to be protected include ectoparasites (arthropods, acarines, etc.) and endoparasites (helminths, e.g., nematodes, trematodes, cestodes, acanthocephalans, etc.).
The disease or group of diseases described generally as helminthiasis is due to infection of an animal host with parasitic worms known as helminths. The term 'helminths' is meant to include nematodes, trematodes, cestodes and acanthocephalans. Helminthiasis is a prevalent and serious economic problem with domesticated animals such as swine, sheep, horses, cattle, goats, dogs, cats and poultry.
Among the helminths, the group of worms described as nematodes causes widespread and at times serious infection in various species of animals.
Nematodes that are contemplated to be treated by the compounds of the invention include, without limitation, the following genera: Acanthocheilonema, Aelurostrongylus, Ancylo stoma, Angiostrongylus, Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema,
Diphyllobothrium, Dirofilaria, Dracunculus, Enterobius, Filaroides, Haemonchus,
Heterakis, Lagochilascaris, Loa, Mansonella, Muellerius, Necator, Nematodirus,
Oesophagostomum, Ostertagia, Oxyuris, Parafilaria, Parascaris, Physaloptera,
Protostrongylus, Setaria, Spirocerca, Stephanofilaria, Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichonema, Trichostrongylus, Trichuris, Uncinaria and Wuchereria.
Of the above, the most common genera of nematodes infecting the animals referred to above are Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema,
Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Certain of these, such as Nematodirus, Cooperia and
Oesophagostomum attack primarily the intestinal tract while others, such as Haemonchus and Ostertagia, are more prevalent in the stomach while others such as Dictyocaulus are found in the lungs. Still other parasites may be located in other tissues such as the heart and blood vessels, subcutaneous and lymphatic tissue and the like.
Trematodes that are contemplated to be treated by the invention and by the inventive methods include, without limitation, the following genera: Alaria, Fasciola, Nanophyetus, Opisthorchis, Paragonimus and Schistosoma.
Cestodes that are contemplated to be treated by the invention and by the inventive methods include, without limitation, the following genera: Diphyllobothrium, Diplydium, Spirometra and Taenia.
The most common genera of parasites of the gastrointestinal tract of humans are Ancylostoma, Necator, Ascaris, Strongy hides, Trichinella, Capillaria, Trichuris and Enterobius. Other medically important genera of parasites which are found in the blood or other tissues and organs outside the gastrointestinal tract are the filarial worms such as Wuchereria, Brugia, Onchocerca and Loa, as well as Dracunculus and extra intestinal stages of the intestinal worms Strongyloides and Trichinella.
Numerous other helminth genera and species are known to the art, and are also contemplated to be treated by the compounds of the invention. These are enumerated in great detail in Textbook of Veterinary Clinical Parasitology, Volume 1, Helminths, E. J. L.
Soulsby, F. A. Davis Co., Philadelphia, Pa.; Helminths, Arthropods and Protozoa, (6thEdition of Monnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby, Williams and Wilkins Co., Baltimore, Md.
The compounds of the invention may be effective against a number of animal ectoparasites (e.g., arthropod ectoparasites of mammals and birds).
Insect and acarine pests include, e.g., biting insects such as flies and mosquitoes, mites, ticks, lice, fleas, true bugs, parasitic maggots, and the like. Adult flies include, e.g., the horn fly or Haematobia irritans, the horse fly or Tabanus spp., the stable fly or Stomoxys calcitrans, the black fly or Simulium spp., the deer fly or Chrysops spp., the louse fly or Melophagus ovinus, and the tsetse fly or Glossina spp. Parasitic fly maggots include, e.g., the bot fly {Oestrus ovis and Cuterebra spp.), the blow fly or Phaenicia spp., the screwworm or Cochliomyia hominivorax, the cattle grub or
Hypoderma spp., the fleeceworm and the Gastrophilus of horses. Mosquitoes include, for example, Culex spp., Anopheles spp. and Aedes spp..
Mites include Mesostigmalphatalpha spp., e.g. mesostigmatids such as the chicken mite, Dermalphanyssus galphallinalphae; itch or scab mites such as Sarcoptidae spp. for example, Salpharcoptes scalphabiei; mange mites such as Psoroptidae spp. including Chorioptes bovis and Psoroptes ovis; chiggers, e.g. Trombiculidae spp. for example the North American chigger, Trombicula alfreddugesi.
Ticks include, e.g., soft-bodied ticks including Argasidae spp. for example
Argalphas spp. and Ornithodoros spp.; hard-bodied ticks including Ixodidae spp., for example Rhipicephalphalus sanguineus, Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Ixodes scapularis and other Rhipicephalus spp. (including the former Boophilus genera).
Lice include, e.g., sucking lice, e.g., Menopon spp.
and Bovicola spp.; biting lice, e.g., Haematopinus spp., Linognathus spp. and Solenopotes spp.
Fleas include, e.g., Ctenocephalides spp., such as dog flea (Ctenocephalides canis) and cat flea {Ctenocephalides felis); Xenopsylla spp. such as oriental rat flea {Xenopsylla cheopis); and Pulex spp. such as human flea {Pulex irritans).
True bugs include, e.g., Cimicidae or e.g., the common bed bug {Cimex lectularius); Triatominae spp. including triatomid bugs also known as kissing bugs; for example
Rhodnius prolixus and Triatoma spp..
Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks and helminths cause tremendous losses to the livestock and companion animal sectors. Arthropod parasites also are a nuisance to humans and can vector disease-causing organisms in humans and animals.
Numerous other parasitic invertebrate pests are known to the art, and are also contemplated to be treated by the compounds of the invention. These are enumerated in great detail in Medical and Veterinary Entomology, D. S. Kettle, John Wiley AND Sons, New York and Toronto; Control of Arthropod Pests of Livestock: A Review of Technology, R. O. Drummand, J. E. George, and S. E. Kunz, CRC Press, Boca Raton, Fla.
The present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http://www.who.int/malaria/vector_control/irs/en/). In one embodiment, the method for controlling pests comprises applying the compositions of the invention to the target pests, to their locus or to a surface or substrate by brushing, rolling, spraying, spreading or dipping. By way of example, an IRS (indoor residual spraying) application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention. In another embodiment, it is contemplated to apply such compositions to a substrate such as non- woven or a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
In one embodiment, the method for controlling such pests comprises applying a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate. Such application may be made by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the invention. By way of example, an IRS application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention so as to provide effective residual pesticidal activity on the surface. In another embodiment, it is contemplated to apply such compositions for residual control of pests on a substrate such as a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
Substrates including non- woven, fabrics or netting to be treated may be made of natural fibres such as cotton, raffia, jute, flax, sisal, hessian, or wool, or synthetic fibres such as polyamide, polyester, polypropylene, polyacrylonitrile or the like. The polyesters are particularly suitable. The methods of textile treatment are know, e.g. from Handbuch Textilveredlung: Band 1 : Ausrustung, Band 2: Farbgebung, Band 3: Beschichtung, Band 4: Umwelttechnik; Verlag: Deutscher Fachverlag; Auflage: 15., uberarbeitete Ausgabe (17. April 2006); ISBN-10: 3866410123; ISBN-13: 978-3866410121, see especially Band 1 : Ausrustung pages 27-198, more preferably on page 118; or WO2008151984 or
WO2003034823 or US5631072 or WO200564072 or WO2006128870 or EP1724392 or WO2005064072 or WO2005113886 or WO2007090739. The compounds of the invention may also be effective against ectoparasites including: flies such as Haematobia (Lyperosia) irritans (horn fly), Simulium spp. (blackfly), Glossina spp. (tsetse flies), Hydrotaea irritans (head fly), Musca autumnalis (face fly), Musca domestica (house fly), Morellia simplex (sweat fly), Tabanus spp. (horse fly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Lucilia cuprina (green blowfly), Calliphora spp. (blowfly), Protophormia spp., Oestrus ovis (nasal botfly), Culicoides spp. (midges), Hippobosca equine, Gastrophilus intestinalis, Gastrophilus haemorrhoidalis and Gastrophilus nasalis; lice such as Bovicola (Damalinia) bovis, Bovicola equi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger, Lignonathus setosus and Trichodectes canis; keds such as Melophagus ovinus; and mites such as Psoroptes spp., Sarcoptes scabei, Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear mites).
Treatments of the invention are by conventional means such as by enteral administration in the form of, for example, tablets, capsules, drinks, drenching preparations, granulates, pastes, boli, feed-through procedures, or suppositories; or by parenteral administration, such as, for example, by injection (including intramuscular, subcutaneous, intravenous, intraperitoneal) or implants; or by nasal administration.
When compounds of the invention are applied in combination with an additional biologically active ingredient, they may be administered separately e.g. as separate compositions. In this case, the biologically active ingredients may be administered simultaneously or sequentially. Alternatively, the biologically active ingredients may be components of one composition.
The compounds of the invention may be administered in a controlled release form, for example in subcutaneous or orally adminstered slow release formulations.
Typically a parasiticidal composition according to the present invention comprises a compound of the invention, optionally in combination with an additional biologically active ingredient, or N-oxides or salts thereof, with one or more pharmaceutically or veterinarily acceptable carriers comprising excipients and auxiliaries selected with regard to the intended route of administration (e.g., oral or parenteral administration such as injection) and in accordance with standard practice. In addition, a suitable carrier is selected on the basis of compatibility with the one or more active ingredients in the composition, including such considerations as stability relative to pH and moisture content. Therefore of note are compounds of the invention for protecting an animal from an invertebrate parasitic pest comprising a parasitically effective amount of a compound of the invention, optionally in combination with an additional biologically active ingredient and at least one carrier.
For parenteral administration including intravenous, intramuscular and
subcutaneous injection, the compounds of the invention can be formulated in suspension, solution or emulsion in oily or aqueous vehicles, and may contain adjuncts such as suspending, stabilizing and/or dispersing agents.
The compounds of the invention may also be formulated for bolus injection or continuous infusion. Pharmaceutical compositions for injection include aqueous solutions of water-soluble forms of active ingredients (e.g., a salt of an active compound), preferably in physiologically compatible buffers containing other excipients or auxiliaries as are known in the art of pharmaceutical formulation. Additionally, suspensions of the active compounds may be prepared in a lipophilic vehicle. Suitable lipophilic vehicles include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or materials such as liposomes.
Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.
In addition to the formulations described supra, the compounds of the invention may also be formulated as a depot preparation. Such long acting formulations may be
administered by implantation (for example, subcutaneously or intramuscularly) or by intramuscular or subcutaneous injection.
The compounds of the invention may be formulated for this route of administration with suitable polymeric or hydrophobic materials (for instance, in an emulsion with a pharmacologically acceptable oil), with ion exchange resins, or as a sparingly soluble derivative such as, without limitation, a sparingly soluble salt.
For administration by inhalation, the compounds of the invention can be delivered in the form of an aerosol spray using a pressurized pack or a nebulizer and a suitable propellant, e.g., without limitation, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane or carbon dioxide. In the case of a pressurized aerosol, the dosage unit may be controlled by providing a valve to deliver a metered amount. Capsules and cartridges of, for example, gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
The compounds of the invention may have favourable pharmacokinetic and pharmacodynamic properties providing systemic availability from oral administration and ingestion. Therefore after ingestion by the animal to be protected, parasiticidally effective concentrations of a compound of the invention in the bloodstream may protect the treated animal from blood-sucking pests such as fleas, ticks and lice. Therefore of note is a composition for protecting an animal from an invertebrate parasite pest in a form for oral administration (i.e. comprising, in addition to a parasiticidally effective amount of a compound of the invention, one or more carriers selected from binders and fillers suitable for oral administration and feed concentrate carriers).
For oral administration in the form of solutions (the most readily available form for absorption), emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, rumen-retention and feed/water/lick blocks, the compounds of the invention can be formulated with binders/fillers known in the art to be suitable for oral administration compositions, such as sugars and sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol), starch (e.g., maize starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g., magnesium stearate), disintegrating agents (e.g., cross-linked polyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments can be added. Pastes and gels often also contain adhesives (e.g., acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate) to aid in keeping the composition in contact with the oral cavity and not being easily ejected.
In one embodiment a composition of the present invention is formulated into a chewable and/or edible product (e.g., a chewable treat or edible tablet). Such a product would ideally have a taste, texture and/or aroma favored by the animal to be protected so as to facilitate oral administration of the compounds of the invention.
If the parasiticidal compositions are in the form of feed concentrates, the carrier is typically selected from high-performance feed, feed cereals or protein concentrates. Such feed concentrate-containing compositions can, in addition to the parasiticidal active ingredients, comprise additives promoting animal health or growth, improving quality of meat from animals for slaughter or otherwise useful to animal husbandry.
These additives can include, for example, vitamins, antibiotics, chemotherapeutics, bacteriostats, fungistats, coccidiostats and hormones.
The compound of the invention may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides.
The formulations for the method of this invention may include an antioxidant, such asBHT (butylated hydroxytoluene). The antioxidant is generally present in amounts of at 0.1- 5 percent (wt/vol). Some of the formulations require a solubilizer, such as oleic acid, to dissolve the active agent, particularly if spinosad is included. Common spreading agents used in these pour-on formulations include isopropyl myristate, isopropyl palmitate,
caprylic/capric acid esters of saturated C12-C18 fatty alcohols, oleic acid, oleyl ester, ethyl oleate, triglycerides, silicone oils and dipropylene glycol methyl ether. The pour-on formulations for the method of this invention are prepared according to known techniques. Where the pour-on is a solution, the parasiticide/insecticide is mixed with the carrier or vehicle, using heat and stirring if required. Auxiliary or additional ingredients can be added to the mixture of active agent and carrier, or they can be mixed with the active agent prior to the addition of the carrier. Pour-on formulations in the form of emulsions or suspensions are similarly prepared using known techniques.
Other delivery systems for relatively hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well-known examples of delivery vehicles or carriers for hydrophobic drugs. In addition, organic solvents such as dimethylsulfoxide may be used, if needed.
The rate of application required for effective parasitic invertebrate pest control (e.g. "pesticidally effective amount") will depend on such factors as the species of parasitic invertebrate pest to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. One skilled in the art can easily determine the pesticidally effective amount necessary for the desired level of parasitic invertebrate pest control. In general for veterinary use, the compounds of the invention are administered in a pesticidally effective amount to an animal, particularly a homeothermic animal, to be protected from parasitic invertebrate pests.
A pesticidally effective amount is the amount of active ingredient needed to achieve an observable effect diminishing the occurrence or activity of the target parasitic invertebrate pest. One skilled in the art will appreciate that the pesticidally effective dose can vary for the various compounds and compositions useful for the method of the present invention, the desired pesticidal effect and duration, the target parasitic invertebrate pest species, the animal to be protected, the mode of application and the like, and the amount needed to achieve a particular result can be determined through simple experimentation.
For oral or parenteral administration to animals, a dose of the compositions of the present invention administered at suitable intervals typically ranges from about 0.01 mg/kg to aboutlOO mg/kg, and preferably from about 0.01 mg/kg to about 30 mg/kg of animal body weight.
Suitable intervals for the administration of the compositions of the present invention to animals range from about daily to about yearly. Of note are administration intervals ranging from about weekly to about once every 6 months. Of particular note are monthly adminstration intervals (i.e. administering the compounds to the animal once every month). Within the scope of the invention, useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals. In one embodiment the invention provides TX for use in controlling and/or preventing insects of the family Curculionidae, preferably in for use in controlling and/or preventing Anthonomus grandis.
Additional examples of insects from the family of Curculionidae. are Anthonomus corvulus, Anthonomus elutus, Anthonomus elongatus, Anthonomus eugenii, Anthonomus consors, Anthonomus haematopus, Anthonomus lecontei, Anthonomus molochinus, Anthonomus morticinus, Anthonomus musculus, Anthonomus nigrinus, Anthonomus phyllocola, Anthonomus pictus, Anthonomus pomorum, Anthonomus quadrigibbus, Anthonomus rectirostris, Anthonomus rubi, Anthonomus santacruzi, Anthonomus signatus, Anthonomus subfasciatus, and Anthonomus tenebrosus.
In one embodiment the invention provides TX for use against Anthonomus grandis in cotton.
In one embodiment the invention provides TX for use in controlling and/or preventing soil pests.
In one embodiment the invention provides TX for use in controlling and/or preventing corn rootworm, in particular for use against corn root worm from the genus Diabrotica.
In one embodiment the invention provides TX for use in controlling and/or preventing Diabrotica virgifera.
In one embodiment the invention provides TX for use in controlling and/or preventing Diabrotica barberi.
In one embodiment the invention provides TX for use in controlling and/or preventing Diabrotica undecimpunctata howardi.
In one embodiment the invention provides TX for use in controlling and/or preventing wireworms, in particular Agriotes spp.
In one embodiment the invention provides TX for use in controlling and/or preventing Agriotes spp. in cereals, potato or corn.
Additional examples of Agriotes spp. include Agriotes lineatus, Agriotes obscurus, Agriotes brevis, Agriotes gurgistanus, Agriotes sputator, Agriotes ustulatus, Ctenicera destructor, and Limonius californicus.
In one embodiment the invention provides TX for use in controlling and/or preventing grubs, in particular white grubs. In one embodiment the invention provides TX for use in controlling and/or preventing Phyllophaga spp., particularly on corn, soybean or cotton.
In one embodiment the invention provides TX for use in controlling and/or preventing Diloboderus spp. particularly on corn, soybean or cotton.
In one embodiment the invention provides TX for use in controlling and/or preventing Popillia japonica, particularly on corn, soybean or cotton.
Additional examples of white grubs include Phyllophaga anxia, Phyllophaga crinite, Phyllophaga subnitida, Diloboderus abderus.
In one embodiment the invention provides TX for use in controlling and/or preventing termites, e.g. on sugarcane.
Examples of termites include Reticulitermes, Coptotermes, Macrotermes,
Microtermes, Globitermes. Specific of subterranean termites include Reticulitermes flavipes, Reticulitermes hesperus, Reticulitermes verginicus, Reticulitermes hageni, Reticulitermes speratus, Reticulitermes lucifugus, Heterotermes aureus, Coptotermes formosanus,
Coptotermes acinaciformis, Coptotermes curvignathus, Nasutitermes exitiosus, Nasutitermes walkeri, Mastotermes darwiniensis, Schedorhinotermes spp, Macrotermes bellicosus, Macrotermes spp., Globitermes sulphureus, Odontotermes spp.. Specific examples of dry wood termites include Incisitermes minor, Marginitermes hubbardi, Cryptotermes brevis, Kalotermes flavicollis. Additional examples of termites include procornitermes spp. and procornitermes araujoi
In one embodiment the invention provides TX for use in controlling and/or preventing subterraneous stinkbugs, e.g. Scaptocoris spp..
In one embodiment the invention provides TX for use in controlling and/or preventing Scaptocoris castaneus, in particular on cereals, soybean or corn.
In one embodiment the invention provides TX for use in controlling and/or preventing cutworms, e.g. agrotis spp..
In one embodiment the invention provides TX for use in controlling and/or preventing Agrotis ipsilon, particularly on cereals, canola, soybean or corn.
In one embodiment the invention provides TX for use in controlling and/or preventing millipedes, e.g. Julus spp..
In one embodiment the invention provides TX for use in controlling and/or preventing Julus spp. , particularly on cereals, canola, soybean & corn. In one embodiment the invention provides TX for use in controlling and/or preventing broca gigante, e.g. Telchin licus, particularly on sugarcane.
In one embodiment the invention provides TX for use in controlling and/or preventing whitefly.
In one embodiment the invention provides TX for use in controlling and/or preventing Bemisia tabaci, particularly on vegetables, cotton, soybean, or potatoes.
In one embodiment the invention provides TX for use in controlling and/or preventing Trialeurodes vaporariorum, particularly on vegetables, cotton, soybean, or potatoes.
In one embodiment the invention provides TX for use in controlling and/or preventing stinkbugs, in particular Euschistus spp.
In one embodiment the invention provides TX for use in controlling and/or preventing Euschistus spp., particularly in soybean.
Examples of stinkbugs include Nezara spp. (e.g. Nezara viridula, Nezara antennata, Nezara hilare), Piezodorus spp. (e.g. Piezodorus guildinii), Acrosternum spp. Euchistus spp. (e.g. Euchistus heros, Euschistus servus), Halyomorpha halys, Plautia crossota, Riptortus clavatus, Rhopalus msculatus, Antestiopsis orbitalus, Dichelops spp. (e.g. Dichelops furcatus, Dichelops melacanthus), Eurygaster spp. (e.g. Eurygaster intergriceps, Eurygaster maura), Oebalus spp. (e.g. Oebalus mexicana, Oebalus poecilus, Oebalus pugnase,
Scotinophara spp. (e.g. Scotinophara lurida, Scotinophara coarctata). Preferred targets include Antestiopsis orbitalus, Dichelops furcatus, Dichelops melacanthus, Euchistus heros, Euschistus servus, Nezara viridula, Nezara hilare, Piezodorus guildinii, Halyomorpha halys. In one embodiment the stinkbug target is Nezara viridula, Piezodorus spp., Acrosternum spp, Euchistus heros.
In one embodiment the invention provides TX for use against rice pests.
In one embodiment the invention provides TX for use against stemborer, particularly in rice.
Examples of stemborers include Chilo sp, Chilo suppressalis, Chilo polychrysus, Chilo auricilius, Scirpophaga spp., Scirpophaga incertulas, Scirpophaga innotata,
Scirpophaga nivella
Sesamia sp, Sesamia inferens.
In one embodiment the invention provides TX for use against leaffolder, particularly in rice. Examples of leaffolders include Cnaphalocrocis spp., Cnaphalocrocis medinalis, Marasmia spp., Marasmia patnalis, Marasmia exigua.
In one embodiment the invention provides TX for use against hoppers, particularly in rice.
Examples of Hoppers include Nephotettix spp., Nephotettix virescens, Nephotettix nigropictus, Nephotettix malayanus, Nephotettix cincticeps, Nilaparvata lugens, Sogatella furcifera.
In one embodiment the invention provides TX for use against gallmidge, particularly in rice.
Examples of Gall midge include Orseolia sp, Orseolia oryzae.
In one embodiment the invention provides TX for use against whorl maggot, particularly in rice.
Examples of whorl maggots include Hydrellia sp, Hydrellia philippina.
In one embodiment the invention provides TX for use against Rice bugs, particularly in rice.
Examples of rice bugs include Leptocorisa sp, Leptocorisa oratorius, Leptocorisa chinensis, Leptocorisa acuta.
In one embodiment the invention provides TX for use against Black bugs, particularly in rice.
Examples of Black bugs include Scotinophara sp, Scotinophara coarctata,
Scotinophara lurida, Scotinophara latiuscula.
In one embodiment the invention provides TX for use against plutella spp..
In one embodiment the invention provides TX for use against Plutella xylostella, particularly in brassica crops.
In one embodiment the invention provides TX for use in controlling and/or preventing insects of the family Curculionidae, preferably in for use in controlling and/or preventing Anthonomus grandis.
Additional examples of insects from the family of Curculionidae. are Anthonomus corvulus, Anthonomus elutus, Anthonomus elongatus, Anthonomus eugenii, Anthonomus consors, Anthonomus haematopus, Anthonomus lecontei, Anthonomus molochinus, Anthonomus morticinus, Anthonomus musculus, Anthonomus nigrinus, Anthonomus phyllocola, Anthonomus pictus, Anthonomus pomorum, Anthonomus quadrigibbus, Anthonomus rectirostris, Anthonomus rubi, Anthonomus santacruzi, Anthonomus signatus, Anthonomus subfasciatus, and Anthonomus tenebrosus.
In one embodiment the invention provides TX for use against Anthonomus grandis in cotton.
In one embodiment the invention provides TX for use in controlling and/or preventing soil pests.
In one embodiment the invention provides TX for use in controlling and/or preventing corn rootworm, in particular for use against corn root worm from the genus Diabrotica.
In one embodiment the invention provides TX for use in controlling and/or preventing corn Diabrotica virgifera.
In one embodiment the invention provides TX for use in controlling and/or preventing corn Diabrotica barberi.
In one embodiment the invention provides TX for use in controlling and/or preventing corn Diabrotica undecimpunctata howardi.
In one embodiment the invention provides TX for use in controlling and/or preventing wireworms, in particular Agriotes spp.
In one embodiment the invention provides TX for use in controlling and/or preventing Agriotes spp. in cereals, potato or corn.
Additional examples of Agriotes spp. include Agriotes lineatus, Agriotes obscurus,
Agriotes brevis, Agriotes gurgistanus, Agriotes sputator, Agriotes ustulatus, Ctenicera destructor, and Limonius californicus.
In one embodiment the invention provides TX for use in controlling and/or preventing grubs, in particular white grubs.
In one embodiment the invention provides TX for use in controlling and/or preventing Phyllophaga spp., particularly on corn, soybean or cotton.
In one embodiment the invention provides TX for use in controlling and/or preventing Diloboderus spp. particularly on corn, soybean or cotton.
In one embodiment the invention provides TX for use in controlling and/or preventing Popillia japonica, particularly on corn, soybean or cotton.
Additional examples of white grubs include Phyllophaga anxia, Phyllophaga crinite, Phyllophaga subnitida, Diloboderus abderus. In one embodiment the invention provides TX for use in controlling and/or preventing termites, e.g. on sugarcane.
Examples of termites include Reticulitermes, Coptotermes, Macrotermes,
Microtermes, Globitermes. Specific of subterranean termites include Reticulitermes flavipes, Reticulitermes hesperus, Reticulitermes verginicus, Reticulitermes hageni, Reticulitermes speratus, Reticulitermes lucifugus, Heterotermes aureus, Coptotermes formosanus,
Coptotermes acinaciformis, Coptotermes curvignathus, Nasutitermes exitiosus, Nasutitermes walkeri, Mastotermes darwiniensis, Schedorhinotermes spp, Macrotermes bellicosus, Macrotermes spp., Globitermes sulphureus, Odontotermes spp.. Specific examples of dry wood termites include Incisitermes minor, Marginitermes hubbardi, Cryptotermes brevis, Kalotermes flavicollis. Additional examples of termites include procornitermes spp. and procornitermes araujoi
In one embodiment the invention provides TX for use in controlling and/or preventing subterraneous stinkbugs, e.g. Scaptocoris spp..
In one embodiment the invention provides TX for use in controlling and/or preventing Scaptocoris castaneus, in particular on cereals, soybean or corn.
In one embodiment the invention provides TX for use in controlling and/or preventing cutworms, e.g. agrotis spp..
In one embodiment the invention provides TX for use in controlling and/or preventing Agrotis ipsilon, particularly on cereals, canola, soybean or corn.
In one embodiment the invention provides TX for use in controlling and/or preventing millipedes, e.g. Julus spp..
In one embodiment the invention provides TX for use in controlling and/or preventing Julus spp. , particularly on cereals, canola, soybean & corn.
In one embodiment the invention provides TX for use in controlling and/or preventing broca gigante, e.g. Telchin licus, particularly on sugarcane.
In one embodiment the invention provides TX for use in controlling and/or preventing whitefly.
In one embodiment the invention provides TX for use in controlling and/or preventing Bemisia tabaci, particularly on vegetables, cotton, soybean, or potatoes.
In one embodiment the invention provides TX for use in controlling and/or preventing Trialeurodes vaporariorum, particularly on vegetables, cotton, soybean, or potatoes. In one embodiment the invention provides TX for use in controlling and/or preventing stinkbugs, in particular Euschistus spp.
In one embodiment the invention provides TX for use in controlling and/or preventing Euschistus spp., particularly in soybean.
Examples of stinkbugs include Nezara spp. (e.g. Nezara viridula, Nezara antennata,
Nezara hilare), Piezodorus spp. (e.g. Piezodorus guildinii), Acrosternum spp. Euchistus spp. (e.g. Euchistus heros, Euschistus servus), Halyomorpha halys, Plautia crossota, Riptortus clavatus, Rhopalus msculatus, Antestiopsis orbitalus, Dichelops spp. (e.g. Dichelops furcatus, Dichelops melacanthus), Eurygaster spp. (e.g. Eurygaster intergriceps, Eurygaster maura), Oebalus spp. (e.g. Oebalus mexicana, Oebalus poecilus, Oebalus pugnase,
Scotinophara spp. (e.g. Scotinophara lurida, Scotinophara coarctata). Preferred targets include Antestiopsis orbitalus, Dichelops furcatus, Dichelops melacanthus, Euchistus heros, Euschistus servus, Nezara viridula, Nezara hilare, Piezodorus guildinii, Halyomorpha halys. In one embodiment the stinkbug target is Nezara viridula, Piezodorus spp., Acrosternum spp, Euchistus heros.
In one embodiment the invention provides TX for use against rice pests.
In one embodiment the invention provides TX for use against stemborer, particularly in rice.
Examples of stemborers include Chilo sp, Chilo suppressalis, Chilo polychrysus, Chilo auricilius, Scirpophaga spp., Scirpophaga incertulas, Scirpophaga innotata,
Scirpophaga nivella
Sesamia sp, Sesamia inferens.
In one embodiment the invention provides TX for use against leaffolder, particularly in rice.
Examples of leaffolders include Cnaphalocrocis spp., Cnaphalocrocis medinalis,
Marasmia spp., Marasmia patnalis, Marasmia exigua.
In one embodiment the invention provides TX for use against hoppers, particularly in rice.
Examples of Hoppers include Nephotettix spp., Nephotettix virescens, Nephotettix nigropictus, Nephotettix malayanus, Nephotettix cincticeps, Nilaparvata lugens, Sogatella furcifera.
In one embodiment the invention provides TX for use against gallmidge, particularly in rice. Examples of Gall midge include Orseolia sp, Orseolia oryzae.
In one embodiment the invention provides TX for use against whorl maggot, particularly in rice.
Examples of whorl maggots include Hydrellia sp, Hydrellia philippina.
In one embodiment the invention provides TX for use against Rice bugs, particularly in rice.
Examples of rice bugs include Leptocorisa sp, Leptocorisa oratorius, Leptocorisa chinensis, Leptocorisa acuta.
In one embodiment the invention provides TX for use against Black bugs, particularly in rice.
Examples of Black bugs include Scotinophara sp, Scotinophara coarctata,
Scotinophara lurida, Scotinophara latiuscula.
In one embodiment the invention provides TX for use against plutella spp..
In one embodiment the invention provides TX for use against Plutella xylostella, particularly in brassica crops.
The term "useful plants" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate -resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.
The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus. Examples of such plants are: YieldGard® (maize variety that expresses a CrylA(b) toxin); YieldGard Rootworm® (maize variety that expresses a CryIIIB(bl) toxin); YieldGard Plus® (maize variety that expresses a CrylA(b) and a CrylllB(bl) toxin); Starlink® (maize variety that expresses a Cry9(c) toxin); Herculex I® (maize variety that expresses a CryIF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylA(c) toxin); Bollgard I® (cotton variety that expresses a CrylA(c) toxin); Bollgard II® (cotton variety that expresses a CrylA(c) and a CryllA(b) toxin); VIPCOT® (cotton variety that expresses a VIP toxin); NewLeaf® (potato variety that expresses a CrylllA toxin); Nature- Gard® Agrisure® GT Advantage (GA21 glyphosate -tolerant trait), Agrisure® CB
Advantage (Btl 1 corn borer (CB) trait), Agrisure® RW (corn rootworm trait) and Protecta®.
The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
The term "locus" of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.
The term "plant propagation material" is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.
The compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.
The term "plant" or "useful plants" as used herein includes seedlings, bushes and trees. The term "crops" is to be understood as including also crop plants which have been so
transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as δ-endotoxins, e.g. CrylAb, CrylAc, CrylF, CrylFa2, Cry2Ab, Cry3A, Cry3Bbl or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vipl, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG- COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases. In the context of the present invention there are to be understood by δ-endotoxins, for example CrylAb, CrylAc, CrylF, CrylFa2, Cry2Ab, Cry3A, Cry3Bbl or Cry9C, or vegetative insecticidal proteins (Vip), for example Vipl, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated CrylAb, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810). Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl- type deoxyribonucleic acids and their preparation are known, for example, from WO
95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available.
Examples of such plants are: YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bbl toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bbl toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a CrylFa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a Cryl Ac toxin);
Bollgard I® (cotton variety that expresses a Cryl Ac toxin); Bollgard II® (cotton variety that expresses a Cryl Ac and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a CrylAb toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); NatureGard ®, Agrisure® GT Advantage (GA21 glyphosate -tolerant trait), Agrisure® CB Advantage (Btl 1 corn borer (CB) trait) and Protecta®.
Further examples of such transgenic crops are:
1. Bill Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer {Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cryl Ab toxin. Btl 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Btl76 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer {Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CrylAb toxin. Btl 76 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bbl toxin and has resistance to certain Coleoptera insects.
5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-l 160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry IF for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 x MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a Cryl Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), BoUgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.
Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
In order to apply a compound of formula (I*) as an insecticide, acaricide, nematicide or molluscicide to a pest, a locus of pest, or to a plant susceptible to attack by a pest, a compound of formula (I*) is usually formulated into a composition which includes, in addition to the compound of formula (I*), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (I*). The composition is generally used for the control of pests such that a compound of formula (I*) is applied at a rate of from 0. lg to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
When used in a seed dressing, a compound of formula (I*) is used at a rate of 0.000 lg to lOg (for example 0.00 lg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
In another aspect the present invention provides an insecticidal, acaricidal, nematicidal or molluscicidal composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I*) and a suitable carrier or diluent therefor. The composition is preferably an insecticidal, acaricidal, nematicidal or molluscicidal composition.
The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (I*).
Dustable powders (DP) may be prepared by mixing a compound of formula (I*) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulfur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
Soluble powders (SP) may be prepared by mixing a compound of formula (I*) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG). Wettable powders (WP) may be prepared by mixing a compound of formula (I*) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound of formula (I*) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I*) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (I*) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulfates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (I*) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).
Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (I*) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or
methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as Cs-Cio fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (I*) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (I*) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I*). SCs may be prepared by ball or bead milling the solid compound of formula (I*) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of formula (I*) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
Aerosol formulations comprise a compound of formula (I*) and a suitable propellant (for example n-butane). A compound of formula (I*) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
A compound of formula (I*) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I*) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula (I*) and they may be used for seed treatment. A compound of formula (I*) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (I*)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (I*)).
A compound of formula (I*) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film- forming barrier).
Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (for example sodium lauryl sulfate), salts of sulfonated aromatic compounds (for example sodium dodecylbenzenesulfonate, calcium
dodecylbenzenesulfonate, butylnaphthalene sulfonate and mixtures of sodium di- z'sopropyl- and tri-z'sopropyl-naphthalene sulfonates), ether sulfates, alcohol ether sulfates (for example sodium laureth-3-sulfate), ether carboxylates (for example sodium laureth-3- carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and
tetraphosphoric acid; additionally these products may be ethoxylated), sulfosuccinamates, paraffin or olefine sulfonates, taurates and lignosulfonates.
Suitable SFAs of the amphoteric type include betaines, propionates and glycinates. Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
A compound of formula (I*) may be applied by any of the known means of applying pesticidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or
incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
A compound of formula (I*) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (I*) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.
A compound of formula (I*) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types include granules of fertiliser. The mixtures preferably contain up to 25% by weight of the compound of formula (I*).
The invention therefore also provides a fertiliser composition comprising a fertiliser and a compound of formula (I*).
The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity. The compound of formula I (herein after abbreviated by the term "TX" thus means a compound encompassed by the compounds of formula I, or preferably the term "TX" refers to a compound selected from the Tables 1 to 12 and A) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients (component (B)) such as a pesticide (insect, acarine, mollusc and nematode pesticide), fungicide, synergist, herbicide, safener or plant growth regulator where appropriate. The activity of the compositions according to the invention may thereby be broadened considerably and may have surprising advantages which can also be described, in a wider sense, as synergistic activity. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; provide a composition demonstrating better plant/crop tolerance by reducing phytotoxicity; provide a composition controlling insects in their different development stages; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the TX; or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition. Examples of suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or
5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopr opane carboxylate;
b) Organophosphates, such as, profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl,
pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon;
c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl;
d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or chlorfluazuron;
e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin;
f) Pyrazoles, such as tebufenpyrad and fenpyroximate;
g) Macrolides, such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, or spinosad, spinetoram or azadirachtin;
h) Hormones or pheromones;
i) Organochlorine compounds such as endosulfan, benzene hexachloride, DDT, chlordane or dieldrin;
j) Amidines, such as chlordimeform or amitraz;
k) Fumigant agents, such as chloropicrin, dichloropropane, methyl bromide or metam;
1) Neonicotinoid compounds such as imidacloprid, thiacloprid, acetamiprid, clothianidin, nitenpyram, dinotefuran or thiamethoxam;
m) Diacylhydrazines, such as tebufenozide, chromafenozide or methoxyfenozide;
n) Diphenyl ethers, such as diofenolan or pyriproxifen;
o) Indoxacarb;
p) Chlorfenapyr;
q) Pymetrozine or pyrifluquinazon;
r) Spirotetramat, spirodiclofen or spiromesifen;
s) Flubendiamide, chloranthraliniprole, or cyanthraniliprole;
t) Cyenopyrafen or cyflumetofen; or
u) Sulfoxaflor. In addition to the major chemical classes of pesticide listed above, other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition. For instance, selective insecticides for particular crops, for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed. Alternatively insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron).
The following mixtures of the compounds of formula I with active ingredients are preferred, wherein the term "TX" refers to a compound as defined above:
an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX,
an acaricide selected from the group of substances consisting of l,l-bis(4-chlorophenyl)-2- ethoxyethanol (IUPAC name) (910) + TX, 2,4-dichlorophenyl benzenesulfonate
(IUP AC/Chemical Abstracts name) ( 1059) + TX, 2-fhioro-N-methyl-N- 1 - naphthylacetamide (IUPAC name) (1295) + TX, 4-chlorophenyl phenyl sulfone (IUPAC name) (981) + TX, abamectin (1) + TX, acequinocyl (3) + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, alpha-cypermethrin (202) + TX, amidithion (870) + TX, amidoflumet [CCN] + TX, amidothioate (872) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, aramite (881) + TX, arsenous oxide (882) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azobenzene (IUPAC name) (888) + TX, azocyclotin (46) + TX, azothoate (889) + TX, benomyl (62) + TX, benoxafos (alternative name) [CCN] + TX, benzoximate (71) + TX, benzyl benzoate (IUPAC name) [CCN] + TX, bifenazate (74) + TX, bifenthrin (76) + TX, binapacryl (907) + TX, brofenvalerate (alternative name) + TX, bromocyclen (918) + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bromopropylate (94) + TX, buprofezin (99) + TX, butocarboxim (103) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, calcium polysulfide (IUPAC name) (111) + TX, camphechlor (941 ) + TX, carbanolate (943) + TX, carbaryl ( 115) + TX, carbofuran (118) + TX, carbophenothion (947) + TX, CGA 50 39 (development code) (125) + TX, chinomethionat (126) + TX, chlorbenside (959) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorfenapyr (130) + TX, chlorfenethol (968) + TX, chlorfenson (970) + TX, chlorfensulphide (971) + TX, chlorfenvinphos (131) + TX, chlorobenzilate (975) + TX, chloromebuform (977) + TX, chloromethiuron (978) + TX, chloropropylate (983) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, clofentezine (158) + TX, closantel (alternative name) [CCN] + TX, coumaphos ( 174) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos (1010) + TX, cufraneb (1013) + TX, cyanthoate (1020) + TX, cyflumetofen (CAS Reg. No.: 400882-07- 7) + TX, cyhalothrin ( 196) + TX, cyhexatin ( 199) + TX, cypermethrin (201 ) + TX, DCPM (1032) + TX, DDT (219) + TX, demephion (1037) + TX, demephion-0 (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton-0 (1038) + TX, demeton-O-methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulphon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diazinon (227) + TX, dichlofluanid (230) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicofol (242) + TX, dicrotophos (243) + TX, dienochlor ( 1071 ) + TX, dimefox ( 1081 ) + TX, dimethoate (262) + TX, dinactin (alternative name) (653) + TX, dinex (1089) + TX, dinex-diclexine (1089) + TX, dinobuton (269) + TX, dinocap (270) + TX, dinocap-4 [CCN] + TX, dinocap-6 [CCN] + TX, dinocton (1090) + TX, dinopenton (1092) + TX, dinosulfon ( 1097) + TX, dinoterbon (1098) + TX, dioxathion ( 1102) + TX, diphenyl sulfone (IUPAC name) (1103) + TX, disulfiram (alternative name) [CCN] + TX, disulfoton (278) + TX, DNOC (282) + TX, dofenapyn (1113) + TX, doramectin (alternative name) [CCN] + TX, endosulfan (294) + TX, endothion (1121) + TX, EPN (297) + TX, eprinomectin (alternative name) [CCN] + TX, ethion (309) + TX, ethoate-methyl (1134) + TX, etoxazole (320) + TX, etrimfos (1142) + TX, fenazaflor (1147) + TX, fenazaquin (328) + TX, fenbutatin oxide (330) + TX, fenothiocarb (337) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fenpyroximate (345) + TX, fenson (1157) + TX, fentrifanil (1161) + TX, fenvalerate (349) + TX, fipronil (354) + TX, fluacrypyrim (360) + TX, fluazuron ( 1166) + TX, flubenzimine ( 1167) + TX, flucycloxuron (366) + TX, flucythrinate (367) + TX, fhienetil (1169) + TX, flufenoxuron (370) + TX, fhimethrin (372) + TX, fluorbenside (1174) + TX, fluvalinate (1184) + TX, FMC 1137
(development code) (1185) + TX, formetanate (405) + TX, formetanate hydrochloride (405) + TX, formothion (1192) + TX, formparanate (1193) + TX, gamma-HCH (430) + TX, glyodin (1205) + TX, halfenprox (424) + TX, heptenophos (432) + TX, hexadecyl cyclopropanecarboxylate (IUPAC/Chemical Abstracts name) (1216) + TX, hexythiazox (441) + TX, iodomethane (IUPAC name) (542) + TX, isocarbophos (alternative name) (473) + TX, isopropyl O-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, lindane (430) + TX, lufenuron (490) + TX, malathion (492) + TX, malonoben (1254) + TX, mecarbam (502) + TX, mephosfolan (1261) + TX, mesulfen (alternative name) [CCN] + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methidathion (529) + TX, methiocarb (530) + TX, methomyl (531) + TX, methyl bromide (537) + TX, metolcarb (550) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naled (567) + TX, NC-184 (compound code) + TX, NC-512 (compound code) + TX, nifiuridide (1309) + TX, nikkomycins
(alternative name) [CCN] + TX, nitrilacarb (1313) + TX, nitrilacarb 1 :1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydeprofos (1324) + TX,
oxydisulfoton ( 1325) + TX, pp'-DDT (219) + TX, parathion (615) + TX, permethrin (626) + TX, petroleum oils (alternative name) (628) + TX, phenkapton (1330) + TX, phenthoate (631) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX, phosphamidon (639) + TX, phoxim (642) + TX, pirimiphos- methyl (652) + TX, polychloroterpenes (traditional name) (1347) + TX, polynactins (alternative name) (653) + TX, proclonol (1350) + TX, profenofos (662) + TX, promacyl (1354) + TX, propargite (671) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothoate (1362) + TX, pyrethrin I (696) + TX, pyrethrin ll (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, quinalphos (711) + TX, quintiofos (1381) + TX, R-1492 (development code) (1382) + TX, RA-17 (development code) (1383) + TX, rotenone (722) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, sophamide (1402) + TX, spirodiclofen (738) + TX, spiromesifen (739) + TX, SSI-121 (development code) (1404) + TX, sulfiram (alternative name) [CCN] + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulphur (754) + TX, SZI-121 (development code) (757) + TX, tau-fluvalinate (398) + TX, tebufenpyrad (763) + TX, TEPP (1417) + TX, terbam (alternative name) + TX, tetrachlorvinphos (777) + TX, tetradifon (786) + TX,
tetranactin (alternative name) (653) + TX, tetrasul (1425) + TX, thiafenox (alternative name) + TX, thiocarboxime (1431) + TX, thiofanox (800) + TX, thiometon (801) + TX, thioquinox (1436) + TX, thuringiensin (alternative name) [CCN] + TX, triamiphos (1441) + TX, triarathene (1443) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trifenofos (1455) + TX, trinactin (alternative name) (653) + TX, vamidothion (847) + TX, vaniliprole [CCN] and YI-5302 (compound code) + TX, an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX,
an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX,
an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX,
a bactericide selected from the group of substances consisting of 1 -hydroxy- lH-pyridine-2- thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1105) + TX, dodicin (1112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308) + TX, nitrapyrin (580) + TX, octhilinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (611) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole (658) + TX, streptomycin (744) + TX, streptomycin sesquisulfate (744) + TX, tecloftalam (766) + TX, and thiomersal (alternative name) [CCN] + TX,
a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis
(alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX,
Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51) + TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51) + TX, Bacillus thuringiensis subsp. tenebrionis (scientific name) (51) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii
(alternative name) (54) + TX, Chrysoperla carnea (alternative name) (151) + TX,
Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV
(alternative name) (191) + TX, Dacnusa sibirica (alternative name) (212) + TX,
Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternative name) (300) + TX, Helicoverpa zea NPV
(alternative name) (431) + TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, Hippodamia convergens (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491) + TX, Mamestra brassicae NPV (alternative name) (494) + TX, Metaphycus helvolus (alternative name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var. anisopliae (scientific name) (523) + TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575) + TX, Orius spp. (alternative name) (596) + TX, Paecilomyces fumosoroseus (alternative name) (613) + TX, Phytoseiulus persimilis (alternative name) (644) + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741) + TX, Steinernema bibionis (alternative name) (742) + TX, Steinernema carpocapsae (alternative name) (742) + TX, Steinernema feltiae (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp. (alternative name) (826) + TX, Typhlodromus occidentalis (alternative name) (844) and Verticillium lecanii (alternative name) (848) + TX,
a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537) + TX,
a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfiuron (alternative name) [CCN] + TX, tepa
[CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa (alternative name)
[CCN] + TX, tretamine (alternative name) [CCN] and uredepa (alternative name) [CCN] + TX,
an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-l-yl acetate with (E)-dec-5-en-l-ol (IUPAC name) (222) + TX, (E)-tridec-4-en-l-yl acetate (IUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541 ) + TX, (E,Z)-tetradeca-4, 10-dien- 1 -yl acetate (IUPAC name) (779) + TX, (Z)-dodec-7-en- 1 -yl acetate (IUPAC name) (285) + TX, ( )-hexadec-l 1-enal (IUPAC name) (436) + TX, (Z)- hexadec- 11 -en- 1 -yl acetate (IUPAC name) (437) + TX, (Z)-hexadec- 13 -en- 11 -yn- 1 -yl acetate (IUPAC name) (438) + TX, (Z)-icos-13-en-10-one (IUPAC name) (448) + TX, (Z)-tetradec-7-en- 1 -al (IUPAC name) (782) + TX, fZ)-tetradec-9-en- 1 -ol (IUPAC name) (783) + TX, (Z)-tetradec-9-en-l-yl acetate (IUPAC name) (784) + TX, (7E,9Z)-dodeca- 7,9-dien-l-yl acetate (IUPAC name) (283) + TX, (9Z,1 lE)-tetradeca-9,l 1-dien-l-yl acetate (IUPAC name) (780) + TX, (9Z, 12E)-tetradeca-9,12-dien-l-yl acetate (IUPAC name) (781) + TX, 14-methyloctadec-l-ene (IUPAC name) (545) + TX, 4-methylnonan-5-ol with 4- methylnonan-5-one (IUPAC name) (544) + TX, alpha-multistriatin (alternative name) [CCN] + TX, brevicomin (alternative name) [CCN] + TX, codlelure (alternative name) [CCN] + TX, codlemone (alternative name) (167) + TX, cuelure (alternative name) (179) + TX, disparlure (277) + TX, dodec-8-en-l-yl acetate (IUPAC name) (286) + TX, dodec- 9-en-l-yl acetate (IUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-l-yl acetate (IUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4-methyloctanoate (IUPAC name) (317) + TX, eugenol (alternative name) [CCN] + TX, frontalin (alternative name) [CCN] + TX, gossy lure (alternative name) (420) + TX, grandlure (421) + TX, grandlure I (alternative name) (421) + TX, grandlure II (alternative name) (421) + TX, grandlure III (alternative name) (421) + TX, grandlure IV (alternative name) (421) + TX, hexalure [CCN] + TX, ipsdienol (alternative name) [CCN] + TX, ipsenol (alternative name) [CCN] + TX, japonilure (alternative name) (481) + TX, lineatin (alternative name) [CCN] + TX, litlure (alternative name) [CCN] + TX, looplure (alternative name) [CCN] + TX, medlure [CCN] + TX, megatomoic acid (alternative name) [CCN] + TX, methyl eugenol (alternative name) (540) + TX, muscalure (563) + TX, octadeca-2,13-dien-l-yl acetate (IUPAC name) (588) + TX, octadeca-3,13-dien-l-yl acetate (IUPAC name) (589) + TX, orfralure (alternative name) [CCN] + TX, oryctalure (alternative name) (317) + TX, ostramone (alternative name) [CCN] + TX, siglure [CCN] + TX, sordidin (alternative name) (736) + TX, sulcatol (alternative name) [CCN] + TX, tetradec-1 1-en-l-yl acetate (IUPAC name) (785) + TX, trimedlure (839) + TX, trimedlure A (alternative name) (839) + TX, trimedlure Bi (alternative name) (839) + TX, trimedlure B2 (alternative name) (839) + TX, trimedlure C (alternative name) (839) and trunc-call (alternative name) [CCN] + TX, an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1 137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX,
an insecticide selected from the group of substances consisting of 1-dichloro-l-nitroethane (IUPAC/Chemical Abstracts name) (1058) + TX, l ,l-dichloro-2,2-bis(4-ethylphenyl)ethane (IUPAC name) (1056), + TX, 1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3-dichloropropene (IUPAC name) (1063) + TX, l-bromo-2-chloroethane (IUPAC/Chemical Abstracts name) (916) + TX, 2,2,2-trichloro-l- (3,4-dichlorophenyl)ethyl acetate (IUPAC name) (1451) + TX, 2,2-dichlorovinyl 2- ethylsulphinylethyl methyl phosphate (IUPAC name) (1066) + TX, 2-(l ,3-dithiolan-2- yl)phenyl dimethylcarbamate (IUPAC/ Chemical Abstracts name) (1 109) + TX, 2-(2- butoxyethoxy)ethyl thiocyanate (IUPAC/Chemical Abstracts name) (935) + TX, 2-(4,5- dimethyl-l,3-dioxolan-2-yl)phenyl methylcarbamate (IUPAC/ Chemical Abstracts name) (1084) + TX, 2-(4-chloro-3,5-xylyloxy)ethanol (IUPAC name) (986) + TX, 2-chlorovinyl diethyl phosphate (IUPAC name) (984) + TX, 2-imidazolidone (IUPAC name) (1225) + TX, 2-isovalerylindan-l,3-dione (IUPAC name) (1246) + TX, 2-methyl(prop-2- ynyl)aminophenyl methylcarbamate (IUPAC name) (1284) + TX, 2-thiocyanatoethyl laurate (IUPAC name) (1433) + TX, 3-bromo-l-chloroprop-l-ene (IUPAC name) (917) + TX, 3 -methyl- l-phenylpyrazol-5-yl dimethylcarbamate (IUPAC name) (1283) + TX, 4- methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate (IUPAC name) (1285) + TX, 5,5- dimethyl-3-oxocyclohex-l-enyl dimethylcarbamate (IUPAC name) (1085) + TX, abamectin (1) + TX, acephate (2) + TX, acetamiprid (4) + TX, acethion (alternative name) [CCN] + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, acrylonitrile (IUPAC name) (861) + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, aldrin (864) + TX, allethrin (17) + TX, allosamidin (alternative name) [CCN] + TX, allyxycarb (866) + TX, alpha-cypermethrin (202) + TX, alpha-ecdysone (alternative name) [CCN] + TX, aluminium phosphide (640) + TX, amidithion (870) + TX, amidothioate (872) + TX, aminocarb (873) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, anabasine (877) + TX, athidathion (883) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azadirachtin (alternative name) (41) + TX, azamethiphos (42) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azothoate (889) + TX, Bacillus thuringiensis delta endotoxins (alternative name) (52) + TX, barium hexafluorosilicate (alternative name) [CCN] + TX, barium polysulfide
(IUPAC/Chemical Abstracts name) (892) + TX, barthrin [CCN] + TX, Bayer 22/190 (development code) (893) + TX, Bayer 22408 (development code) (894) + TX, bendiocarb (58) + TX, benfuracarb (60) + TX, bensultap (66) + TX, beta-cyfluthrin (194) + TX, beta-cypermethrin (203) + TX, bifenthrin (76) + TX, bioallethrin (78) + TX, bioallethrin S-cyclopentenyl isomer (alternative name) (79) + TX, bioethanomethrin [CCN] + TX, biopermethrin (908) + TX, bioresmethrin (80) + TX, bis(2-chloroethyl) ether (IUPAC name) (909) + TX, bistrifluron (83) + TX, borax (86) + TX, brofenvalerate (alternative name) + TX, bromfenvinfos (914) + TX, bromocyclen (918) + TX, bromo-DDT
(alternative name) [CCN] + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bufencarb (924) + TX, buprofezin (99) + TX, butacarb (926) + TX, butathiofos (927) + TX, butocarboxim (103) + TX, butonate (932) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, calcium arsenate [CCN] + TX, calcium cyanide (444) + TX, calcium polysulfide (IUPAC name) (111) + TX, camphechlor (941 ) + TX, carbanolate (943) + TX, carbaryl ( 115) + TX, carbofuran (118) + TX, carbon disulfide (IUPAC/Chemical Abstracts name) (945) + TX, carbon
tetrachloride (IUPAC name) (946) + TX, carbophenothion (947) + TX, carbosulfan (119) + TX, cartap (123) + TX, cartap hydrochloride (123) + TX, cevadine (alternative name) (725) + TX, chlorbicyclen (960) + TX, chlordane (128) + TX, chlordecone (963) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorethoxyfos (129) + TX, chlorfenapyr (130) + TX, chlorfenvinphos (131) + TX, chlorfluazuron (132) + TX, chlormephos (136) + TX, chloroform [CCN] + TX, chloropicrin (141) + TX, chlorphoxim (989) + TX, chlorprazophos (990) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, chromafenozide (150) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, cis-resmethrin
(alternative name) + TX, cismethrin (80) + TX, clocythrin (alternative name) + TX, cloethocarb (999) + TX, closantel (alternative name) [CCN] + TX, clothianidin (165) + TX, copper acetoarsenite [CCN] + TX, copper arsenate [CCN] + TX, copper oleate
[CCN] + TX, coumaphos (174) + TX, coumithoate (1006) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos ( 1010) + TX, crufomate ( 1011 ) + TX, cryolite
(alternative name) (177) + TX, CS 708 (development code) (1012) + TX, cyanofenphos (1019) + TX, cyanophos (184) + TX, cyanthoate (1020) + TX, cyclethrin [CCN] + TX, cycloprothrin (188) + TX, cyfluthrin (193) + TX, cyhalothrin (196) + TX, cypermethrin (201) + TX, cyphenothrin (206) + TX, cyromazine (209) + TX, cythioate (alternative name) [CCN] + TX, <i-limonene (alternative name) [CCN] + TX, -tetramethrin
(alternative name) (788) + TX, DAEP (1031) + TX, dazomet (216) + TX, DDT (219) + TX, decarbofuran (1034) + TX, deltamethrin (223) + TX, demephion (1037) + TX, demephion-0 (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton- methyl (224) + TX, demeton-0 (1038) + TX, demeton-O-methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton- S-methylsulphon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diamidafos (1044) + TX, diazinon (227) + TX, dicapthon (1050) + TX, dichlofenthion (1051) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicresyl (alternative name) [CCN] + TX, dicrotophos (243) + TX, dicyclanil (244) + TX, dieldrin (1070) + TX, diethyl 5 -methylpyrazol-3-yl phosphate (IUPAC name) (1076) + TX, diflubenzuron (250) + TX, dilor (alternative name) [CCN] + TX, dimefhithrin [CCN] + TX, dimefox ( 1081 ) + TX, dimetan (1085) + TX, dimethoate (262) + TX, dimethrin (1083) + TX, dimethylvinphos (265) + TX, dimetilan (1086) + TX, dinex (1089) + TX, dinex-diclexine (1089) + TX, dinoprop (1093) + TX, dinosam (1094) + TX, dinoseb (1095) + TX, dinotefuran (271) + TX, diofenolan (1099) + TX, dioxabenzofos (1100) + TX, dioxacarb (1101) + TX, dioxathion (1102) + TX, disulfoton (278) + TX, dithicrofos (1108) + TX, DNOC (282) + TX, doramectin (alternative name) [CCN] + TX, DSP (1115) + TX, ecdysterone (alternative name) [CCN] + TX, EI 1642 (development code) (1118) + TX, emamectin (291) + TX, emamectin benzoate (291 ) + TX, EMPC ( 1120) + TX, empenthrin (292) + TX, endosulfan (294) + TX, endothion (1121) + TX, endrin (1122) + TX, EPBP (1123) + TX, EPN (297) + TX, epofenonane (1124) + TX, eprinomectin (alternative name) [CCN] + TX, esfenvalerate (302) + TX, etaphos (alternative name) [CCN] + TX, ethiofencarb (308) + TX, ethion (309) + TX, ethiprole (310) + TX, ethoate-methyl (1134) + TX, ethoprophos (312) + TX, ethyl formate (IUPAC name) [CCN] + TX, ethyl-DDD
(alternative name) (1056) + TX, ethylene dibromide (316) + TX, ethylene dichloride (chemical name) (1136) + TX, ethylene oxide [CCN] + TX, etofenprox (319) + TX, etrimfos (1142) + TX, EXD (1143) + TX, famphur (323) + TX, fenamiphos (326) + TX, fenazaflor (1147) + TX, fenchlorphos (1148) + TX, fenethacarb (1149) + TX, fenfhithrin (1150) + TX, fenitrothion (335) + TX, fenobucarb (336) + TX, fenoxacrim (1153) + TX, fenoxycarb (340) + TX, fenpirithrin (1155) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fensulfothion (1158) + TX, fenthion (346) + TX, fenthion-ethyl [CCN] + TX, fenvalerate (349) + TX, fipronil (354) + TX, flonicamid (358) + TX, flubendiamide (CAS. Reg. No.: 272451-65-7) + TX, flucofuron (1168) + TX,
flucycloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1169) + TX, flufenerim [CCN] + TX, flufenoxuron (370) + TX, flufenprox (1171) + TX, fhimethrin (372) + TX, fluvalinate (1184) + TX, FMC 1137 (development code) (1185) + TX, fonofos (1191) + TX, formetanate (405) + TX, formetanate hydrochloride (405) + TX, formothion (1192) + TX, formparanate ( 1193) + TX, fosmethilan ( 1194) + TX, fospirate ( 1195) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furathiocarb (412) + TX, furethrin (1200) + TX, gamma-cyhalothrin (197) + TX, gamma-HCH (430) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, GY-81 (development code) (423) + TX, halfenprox (424) + TX, halofenozide (425) + TX, HCH (430) + TX, HEOD (1070) + TX, heptachlor (1211) + TX, heptenophos (432) + TX, heterophos [CCN] + TX, hexaflumuron (439) + TX, HHDN (864) + TX, hydramethylnon (443) + TX, hydrogen cyanide (444) + TX, hydroprene (445) + TX, hyquincarb (1223) + TX, imidacloprid (458) + TX, imiprothrin (460) + TX, indoxacarb (465) + TX, iodomethane (IUPAC name) (542) + TX, IPSP (1229) + TX, isazofos (1231) + TX, isobenzan (1232) + TX, isocarbophos (alternative name) (473) + TX, isodrin (1235) + TX, isofenphos (1236) + TX, isolane (1237) + TX, isoprocarb (472) + TX, isopropyl 0-(methoxy- aminothiophosphoryl)salicylate (IUPAC name) (473) + TX, isoprothiolane (474) + TX, isothioate (1244) + TX, isoxathion (480) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, juvenile hormone I (alternative name) [CCN] + TX, juvenile hormone II (alternative name) [CCN] + TX, juvenile hormone III (alternative name) [CCN] + TX, kelevan (1249) + TX, kinoprene (484) + TX, lambda-cyhalothrin (198) + TX, lead arsenate [CCN] + TX, lepimectin (CCN) + TX, leptophos (1250) + TX, lindane (430) + TX, lirimfos (1251) + TX, lufenuron (490) + TX, lythidathion (1253) + TX, m-cumenyl methylcarbamate (IUPAC name) (1014) + TX, magnesium phosphide (IUPAC name) (640) + TX, malathion (492) + TX, malonoben (1254) + TX, mazidox (1255) + TX, mecarbam (502) + TX, mecarphon (1258) + TX, menazon (1260) + TX, mephosfolan (1261) + TX, mercurous chloride (513) + TX, mesulfenfos (1263) + TX, metaflumizone (CCN) + TX, metam (519) + TX, metam-potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methanesulphonyl fluoride (IUPAC/Chemical Abstracts name) (1268) + TX, methidathion (529) + TX, methiocarb (530) + TX, methocrotophos (1273) + TX, methomyl (531) + TX,
methoprene (532) + TX, methoquin-butyl (1276) + TX, methothrin (alternative name) (533) + TX, methoxychlor (534) + TX, methoxyfenozide (535) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, methylchloroform (alternative name) [CCN] + TX, methylene chloride [CCN] + TX, metofhithrin [CCN] + TX, metolcarb (550) + TX, metoxadiazone (1288) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, mirex (1294) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naftalofos (alternative name) [CCN] + TX, naled (567) + TX, naphthalene (IUPAC/Chemical Abstracts name) (1303) + TX, NC-170 (development code) (1306) + TX, NC- 184 (compound code) + TX, nicotine (578) + TX, nicotine sulfate (578) + TX, nifluridide (1309) + TX, nitenpyram (579) + TX, nithiazine (1311) + TX, nitrilacarb (1313) + TX, nitrilacarb 1 : 1 zinc chloride complex (1313) + TX, NI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, nornicotine (traditional name) (1319) + TX, novaluron (585) + TX, noviflumuron (586) + TX, 0-5-dichloro-4-iodophenyl 0-ethyl ethylphosphonothioate (IUPAC name) (1057) + TX, O, O-diethyl 0-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate (IUPAC name) (1074) + TX, Ο,Ο-diethyl 0-6-methyl-2-propylpyrimidin-4-yl phosphorothioate (IUPAC name) (1075) + TX, O, O, <7,<7-tetrapropyl dithiopyrophosphate (IUPAC name) (1424) + TX, oleic acid (IUPAC name) (593) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydemeton-methyl (609) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp*-DDT (219) + TX, para-dichlorobenzene [CCN] + TX, parathion (615) + TX, parathion-methyl (616) + TX, penfluron (alternative name) [CCN] + TX, pentachlorophenol (623) + TX, pentachlorophenyl laurate (IUPAC name) (623) + TX, permethrin (626) + TX, petroleum oils (alternative name) (628) + TX, ΡΗ 60-38
(development code) (1328) + TX, phenkapton (1330) + TX, phenothrin (630) + TX, phenthoate (631) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX, phosnichlor (1339) + TX, phosphamidon (639) + TX, phosphine (IUPAC name) (640) + TX, phoxim (642) + TX, phoxim-methyl (1340) + TX, pirimetaphos (1344) + TX, pirimicarb (651) + TX, pirimiphos-ethyl (1345) + TX, pirimiphos-methyl (652) + TX, polychlorodicyclopentadiene isomers (IUPAC name) (1346) + TX, polychloroterpenes (traditional name) (1347) + TX, potassium arsenite [CCN] + TX, potassium thiocyanate [CCN] + TX, prallethrin (655) + TX, precocene I (alternative name) [CCN] + TX, precocene II (alternative name) [CCN] + TX, precocene III (alternative name) [CCN] + TX, primidophos (1349) + TX, profenofos (662) + TX, profluthrin [CCN] + TX, promacyl (1354) + TX, promecarb (1355) + TX, propaphos (1356) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothiofos (686) + TX, prothoate (1362) + TX, protrifenbute [CCN] + TX, pymetrozine (688) + TX, pyraclofos (689) + TX, pyrazophos (693) + TX, pyresmethrin (1367) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridalyl (700) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, pyriproxyfen (708) + TX, quassia (alternative name) [CCN] + TX, quinalphos (711) + TX, quinalphos-methyl (1376) + TX, quinothion ( 1380) + TX, quintiofos ( 1381 ) + TX, R- 1492 (development code) ( 1382) + TX, rafoxanide (alternative name) [CCN] + TX, resmethrin (719) + TX, rotenone (722) + TX, RU 15525 (development code) (723) + TX, RU 25475 (development code) (1386) + TX, ryania (alternative name) (1387) + TX, ryanodine (traditional name) (1387) + TX, sabadilla (alternative name) (725) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, SI- 0205 (compound code) + TX, SI-0404 (compound code) + TX, SI-0405 (compound code) + TX, silafluofen (728) + TX, SN 72129 (development code) (1397) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoride (IUPAC/Chemical Abstracts name) (1399) + TX, sodium hexafluorosilicate (1400) + TX, sodium
pentachlorophenoxide (623) + TX, sodium selenate (IUPAC name) (1401) + TX, sodium thiocyanate [CCN] + TX, sophamide (1402) + TX, spinosad (737) + TX, spiromesifen (739) + TX, spirotetrmat (CCN) + TX, sulcofuron (746) + TX, sulcofuron-sodium (746) + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulphuryl fluoride (756) + TX, sulprofos (1408) + TX, tar oils (alternative name) (758) + TX, tau-fluvalinate (398) + TX, tazimcarb (1412) + TX, TDE (1414) + TX, tebufenozide (762) + TX, tebufenpyrad (763) + TX, tebupirimfos (764) + TX, teflubenzuron (768) + TX, tefluthrin (769) + TX, temephos (770) + TX, TEPP (1417) + TX, terallethrin (1418) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachloroethane [CCN] + TX, tetrachlorvinphos (777) + TX, tetramethrin (787) + TX, theta-cypermethrin (204) + TX, thiacloprid (791) + TX, thiafenox (alternative name) + TX, thiamethoxam (792) + TX, thicrofos (1428) + TX, thiocarboxime (1431) + TX, thiocyclam (798) + TX, thiocyclam hydrogen oxalate (798) + TX, thiodicarb (799) + TX, thiofanox (800) + TX, thiometon (801) + TX, thionazin (1434) + TX, thiosultap (803) + TX, thiosultap-sodium (803) + TX,
thuringiensin (alternative name) [CCN] + TX, tolfenpyrad (809) + TX, tralomethrin (812) + TX, transfluthrin (813) + TX, transpermethrin (1440) + TX, triamiphos (1441) + TX, triazamate (818) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trichlormetaphos-3 (alternative name) [CCN] + TX, trichloronat (1452) + TX, trifenofos (1455) + TX, triflumuron (835) + TX, trimethacarb (840) + TX, triprene (1459) + TX, vamidothion (847) + TX, vaniliprole [CCN] + TX, veratridine (alternative name) (725) + TX, veratrine (alternative name) (725) + TX, XMC (853) + TX, xylylcarb (854) + TX, YI-5302 (compound code) + TX, zeta-cypermethrin (205) + TX, zetamethrin (alternative name) + TX, zinc phosphide (640) + TX, zolaprofos (1469) and ZXI 8901 (development code) (858) + TX, cyantraniliprole [736994-63-19] + TX, chlorantraniliprole [500008-45-7] + TX, cyenopyrafen [560121-52-0] + TX, cyflumetofen [400882-07-7] + TX, pyrifiuquinazon [337458-27-2] + TX, spinetoram [187166-40-1 + 187166-15-0] + TX, spirotetramat [203313-25-1] + TX, sulfoxaflor [946578-00-3] + TX, flufrprole [704886-18-0] + TX, meperfluthrin [915288-13-0] + TX, tetramethylfluthrin
[84937-88-2] + TX,
a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide
(IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb
( 1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, trifenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, pyriprole [394730-71-3] + TX,
a nematicide selected from the group of substances consisting of AKD-3088 (compound code) + TX, l,2-dibromo-3-chloropropane (IUPAC/Chemical Abstracts name) (1045) + TX, 1 ,2-dichloropropane (IUPAC/ Chemical Abstracts name) (1062) + TX, 1,2- dichloropropane with 1,3-dichloropropene (IUPAC name) (1063) + TX, 1,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1,1 -dioxide (IUPAC/Chemical Abstracts name) (1065) + TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980) + TX, 5-methyl- 6-thioxo-l,3,5-thiadiazinan-3-ylacetic acid (IUPAC name) (1286) + TX, 6- isopentenylaminopurine (alternative name) (210) + TX, abamectin (1) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, AZ 60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX,
butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cloethocarb (999) + TX, cytokinins (alternative name) (210) + TX, dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, diamidafos (1044) + TX, dichlofenthion (1051) + TX, dicliphos (alternative name) + TX, dimethoate (262) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ethoprophos (312) + TX, ethylene dibromide (316) + TX, fenamiphos (326) + TX, fenpyrad (alternative name) + TX, fensulfothion (1158) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furfural (alternative name) [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (IUPAC name) (542) + TX, isamidofos (1230) + TX, isazofos (1231) + TX, ivermectin (alternative name) [CCN] + TX, kinetin
(alternative name) (210) + TX, mecarphon (1258) + TX, metam (519) + TX, metam- potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, Myrothecium verrucaria composition (alternative name) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidon (639) + TX, phosphocarb [CCN] + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachlorothiophene (IUPAC/ Chemical Abstracts name) (1422) + TX, thiafenox (alternative name) + TX, thionazin (1434) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, xylenols [CCN] + TX, YI-5302 (compound code) and zeatin (alternative name) (210) + TX, fluensulfone [318290-98-1] + TX,
a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,
a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX,
a rodenticide selected from the group of substances consisting of 2-isovalerylindan-l ,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (1005) + TX, coumatetralyl (175) + TX, crimidine (1009) + TX, difenacoum (246) + TX, difethialone (249) + TX, diphacinone (273) + TX, ergocalciferol (301) + TX,
flocoumafen (357) + TX, fluoroacetamide (379) + TX, flupropadine (1183) + TX, flupropadine hydrochloride (1183) + TX, gamma-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (IUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (IUPAC name) (640) + TX, methyl bromide (537) + TX, norbormide (1318) + TX, phosacetim (1336) + TX, phosphine (IUPAC name) (640) + TX, phosphorus [CCN] + TX, pindone (1341) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371) + TX, scilliroside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoroacetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851) and zinc phosphide (640) + TX,
a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934) + TX, 5-(l,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903) + TX, farnesol with nerolidol (alternative name) (324) + TX, MB- 599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX,
an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc
naphthenate [CCN] and ziram (856) + TX,
a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX,
a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX,
and biologically active compounds selected from the group consisting of azaconazole (60207-31 -0] + TX, bitertanol [70585-36-3] + TX, bromuconazole [116255-48-2] + TX, cyproconazole [94361- 06-5] + TX, difenoconazole [119446-68-3] + TX, diniconazole [83657-24-3] + TX, epoxicon- azole [106325-08-0] + TX, fenbuconazole [114369-43-6] + TX, fluquinconazole [136426-54-5] + TX, flusilazole [85509-19-9] + TX, flutriafol [76674-21-0] + TX, hexaconazole [79983-71-4] + TX, imazalil [35554-44-0] + TX, imibenconazole [86598-92-7] + TX, ipconazole [125225-28-7] + TX, metconazole [125116-23-6] + TX, myclobutanil [88671-89-0] + TX, pefurazoate [101903- 30-4] + TX, penconazole [66246-88-6] + TX, prothioconazole [178928-70-6] + TX, pyrifenox [88283-41-4] + TX, prochloraz [67747-09-5] + TX, propiconazole [60207-90-1] + TX, simeconazole [149508-90-7] + TX, tebuconazole [107534-96-3] + TX, tetraconazole [112281-77- 3] + TX, triadimefon [43121-43-3] + TX, triadimenol [55219-65-3] + TX, triflumizole [99387- 89-0] + TX, triticonazole [131983-72-7] + TX, ancymidol [12771-68-5] + TX, fenarimol [60168- 88-9] + TX, nuarimol [63284-71-9] + TX, bupirimate [41483-43-6] + TX, dimethirimol [5221- 53-4] + TX, ethirimol [23947-60-6] + TX, dodemorph [1593-77-7] + TX, fenpropidine [67306- 00-7] + TX, fenpropimorph [67564-91 -4] + TX, spiroxamine [1 18134-30-8] + TX, tridemorph [81412-43-3] + TX, cyprodinil [121552-61 -2] + TX, mepanipyrim [1 10235-47-7] + TX, pyrimethanil [531 12-28-0] + TX, fenpiclonil [74738-17-3] + TX, fludioxonil [131341 -86-1 ] + TX, benalaxyl [71626-1 1 -4] + TX, furalaxyl [57646-30-7] + TX, metalaxyl [57837-19-1 ] + TX, R-metalaxyl [70630- 17-0] + TX, ofurace [58810-48-3] + TX, oxadixyl [77732-09-3] + TX, benomyl [17804-35-2] + TX, carbendazim [10605-21 -7] + TX, debacarb [62732-91 -6] + TX, fuberidazole [3878-19-1 ] + TX, thiabendazole [148-79-8] + TX, chlozolinate [84332-86-5] + TX, dichlozoline [24201 -58-9] + TX, iprodione [36734-19-7] + TX, myclozoline [54864-61 -8] + TX, procymidone [32809-16-8] + TX, vinclozoline [50471-44-8] + TX, boscalid [188425-85-6] + TX, carboxin [5234-68-4] + TX, fenfuram [24691 -80-3] + TX, flutolanil [66332-96-5] + TX, mepronil [55814-41 -0] + TX, oxycarboxin [5259-88-1 ] + TX, penthiopyrad [183675-82-3] + TX, thifluzamide [130000-40-7] + TX, guazatine [108173-90-6] + TX, dodine [2439-10-3] [1 12-65-2] (free base) + TX, iminoctadine [ 13516-27-3] + TX, azoxystrobin [131860-33-8] + TX, dimoxystrobin [149961 -52-4] + TX, enestroburin {Proc. BCPC, Int. Congr., Glasgow, 2003, 1, 93 } + TX, fluoxastrobin [361377-29-9] + TX, kresoxim-methyl [143390-89-0] + TX, metomi- nostrobin [133408-50-1 ] + TX, trifloxystrobin [141517-21 -7] + TX, orysastrobin [248593-16-0] + TX, picoxystrobin [1 17428-22-5] + TX, pyraclostrobin [175013-18-0] + TX, ferbam [14484-64- 1 ] + TX, mancozeb [8018-01 -7] + TX, maneb [12427-38-2] + TX, metiram [9006-42-2] + TX, propineb [12071 -83-9] + TX, thiram [137-26-8] + TX, zineb [12122-67-7] + TX, ziram [137-30- 4] + TX, captafol [2425-06-1 ] + TX, captan [133-06-2] + TX, dichlofluanid [1085-98-9] + TX, fluoroimide [41205-21 -4] + TX, folpet [133-07-3 ] + TX, tolylfluanid [731 -27-1 ] + TX, bordeaux mixture [801 1 -63-0] + TX, copperhydroxid [20427-59-2] + TX, copperoxychlorid
[1332-40-7] + TX, coppersulfat [7758-98-7] + TX, copperoxid [1317-39-1 ] + TX, mancopper [53988-93-5] + TX, oxine-copper [10380-28-6] + TX, dinocap [131 -72-6] + TX, nitrothal- isopropyl [10552-74-6] + TX, edifenphos [17109-49-8] + TX, iprobenphos [26087-47-8] + TX, isoprothiolane [50512-35-1 ] + TX, phosdiphen [36519-00-3] + TX, pyrazophos [13457-18-6] + TX, tolclofos-methyl [57018-04-9] + TX, acibenzolar-S-methyl [135158-54-2] + TX, anilazine [101 -05-3] + TX, benthiavalicarb [413615-35-7] + TX, blasticidin-S [2079-00-7] + TX, chinomethionat [2439-01 -2] + TX, chloroneb [2675-77-6] + TX, chlorothalonil [1897-45-6] + TX, cyflufenamid [180409-60-3] + TX, cymoxanil [57966-95-7] + TX, dichlone [117-80-6] + TX, diclocymet [139920-32-4] + TX, diclomezine [62865-36-5] + TX, dicloran [99-30-9] + TX, diethofencarb [87130-20-9] + TX, dimethomorph [110488-70-5] + TX, SYP-LI90 (Flumorph) [211867-47-9] + TX, dithianon [3347-22-6] + TX, ethaboxam [162650-77-3] + TX, etridiazole [2593-15-9] + TX, famoxadone [131807-57-3] + TX, fenamidone [161326-34- 7] + TX, fenoxanil [115852-48-7] + TX, fentin [668-34-8] + TX, ferimzone [89269-64-7] + TX, fluazinam [79622- 59-6] + TX, fluopicolide [239110-15-7] + TX, flusulfamide [106917-52-6] + TX, fenhexamid [126833-17-8] + TX, fosetyl-aluminium [39148-24-8] + TX, hymexazol [10004-44-1] + TX, iprovalicarb [140923-17-7] + TX, IKF-916 (Cyazofamid) [120116-88-3] + TX, kasugamycin [6980-18-3] + TX, methasulfocarb [66952-49-6] + TX, metrafenone [220899-03-6] + TX, pencycuron [66063-05-6] + TX, phthalide [27355-22-2] + TX, polyoxins [11113-80-7] + TX, probenazole [27605-76-1] + TX, propamocarb [25606-41-1] + TX, proquinazid [189278-12-4] + TX, pyroquilon [57369-32-1] + TX, quinoxyfen [124495-18-7] + TX, quintozene [82-68-8] + TX, sulphur [7704-34-9] + TX, tiadinil [223580-51-6] + TX, triazoxide [72459-58-6] + TX, tricyclazole [41814-78-2] + TX, triforine [26644-46-2] + TX, validamycin [37248-47-8] + TX, zoxamide (RH7281) [156052-68-5] + TX, mandipropamid [374726-62-2] + TX, isopyrazam
[881685-58-1] + TX, sedaxane [874967-67-6] + TX, 3 -difluoromethyl-1 -methyl- lH-pyrazole-4- carboxylic acid (9-dichloromethylene-l,2,3,4-tetrahydro-l,4-methano-naphthalen-5-yl)-amide (dislosed in WO 2007/048556) + TX, 3-(difluoromethyl)-N-methoxy-l -methyl-N-[l-methyl-2- (2,4,6-trichlorophenyl)ethyl]-lH-Pyrazole-4-carboxamide + TX, 3 -difluoromethyl-1 -methyl- 1H- pyrazole-4-carboxylic acid [2-(2,4-dichlorophenyl)-2-methoxy-l -methyl-ethyl] -amide (disclosed in WO 2008/148570) + TX, l-[4-[4-[(5S)5-(2,6-difluorophenyl)-4,5-dihydro-l,2-oxazol-3-yl]-l,3- thiazol-2-yl]piperidin-l -yl]-2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l -yl]ethanone + TX, l-[4- [4-[5-(2,6-difluorophenyl)-4,5-dihydro-l,2-oxazol-3-yl]-l,3-thiazol-2-yl]piperidin-l -yl]-2-[5-methyl- 3-(trifluoromethyl)-lH-pyrazol-l -yl]ethanone [1003318-67-9], both disclosed in WO 2010/123791, WO 2008/013925, WO 2008/013622 and WO 2011/051243 page 20) +TX, S)-[3-(4-Chloro-2- fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y l]-pyridin-3-yl -methanol + TX, 3-(4-Chloro-2- fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y l]-pyridin-3-yl-methanol + TX, (3- difluoromethyl- 1 -methyl- 1 H-pyrazole-4-carboxylic acid (3 ' ,4' -dichloro-5-fluoro- 1, 1 '- biphenyl-2-yl)-amide (bixafen) + TX, (N- {2-[3-Chloro-5-(trifiuoromethyl)pyridin-2- yl]ethyl}-2-(trifluoromethyl)benzamid (fluopyram) and TX, N-[2-(l ,3- dimethylbutyl)phenyl] -5 -fluoro- 1 ,3 -dimethyl- 1 H-pyrazole-4-carboxamide (Penflufen) and TX, l-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-l-piperidinyl]-2- [5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]ethanone (CAS Reg.-No. : 1003318-67-9, oxathiapiprolin) and TX and 3 -difluoromethyl-1 -methyl- lH-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide (dislosed in WO 2006/087343) + TX.
Throughout this document the expression "composition" stands for the various mixtures or combinations of components TX and (B), for example in a single "ready-mix" form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix", and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the components TX and (B) is not essential for working the present invention.
The compositions according to the invention may also comprise more than one of the active components (B), if, for example, a broadening of the spectrum of disease control is desired. For instance, it may be advantageous in the agricultural practice to combine two or three components (B) with component TX.
The components (B) are known for example from "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition (New edition (02 Nov 2003)); Editor: C. D. S. Tomlin; The British Crop Protection Council, ISBN-10: 1901396134; ISBN-13: 978-1901396133] or its electronic version "e-Pesticide Manual V4.2" or from the website http://www.alanwood.net/pesticides/. Where the components (B) are included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. Tomlin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular component
(B) ; for example, the compound "abamectin" is described under entry number (1). Most of the components (B) are referred to hereinabove by a so-called "common name", the relevant
"ISO common name" or another "common name" being used in individual cases. If the designation is not a "common name", the nature of the designation used instead is given in round brackets for the particular component (B); in that case, the IUPAC name, the
IUPAC/Chemical Abstracts name, a "chemical name", a "traditional name", a "compound name" or a "develoment code" is used or, if neither one of those designations nor a "common name" is used, an "alternative name" is employed.
In the above-mentioned mixtures of compounds of formula I as set forth a the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M)and/or, embodiment (N), and in particular a specific compound listed in the embodiment (A), embodiment (B), embodiment
(C) , embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M)and/or, embodiment (N), with other insecticides, fungicides, herbicides, safeners, adjuvants and the like, the mixing ratios can vary over a large range and are, preferably
100: 1 to 1 :6000, especially 50: 1 to 1 :50, more especially 20: 1 to 1 :20, even more especially 10: 1 to 1 : 10. Those mixing ratios are understood to include, on the one hand, ratios by weight and also, on other hand, molar ratios.
The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of TX with the mixing partner).
Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.
The mixtures comprising a TX selected from Tables 1 to 12 and A and one or more active ingredients as described above can be applied, for example, in a single "ready-mix" form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix", and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the compounds of formula I selected from Tables 1 to 12 and A and the active ingredients as described above is not essential for working the present invention.
The compounds of formula (I*) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Examples of suitable synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole. Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
An example of a rice selective herbicide which may be included is propanil. An example of a plant growth regulator for use in cotton is PIX™.
Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.

Claims

1. A pharmaceutical composition comprising at least one compound of formula (I) of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) for use against parasitic invertebrate pests in or on an animal or in or on a human.
2. A pharmaceutical composition according to claim 1 wherein the pest is a nematode, a trematode, a cestode, a fly, a mite, a trick, a lice, a flea, a true bug or a maggot.
3. A combination product according to claim 1 wherein the animal to be treated is a cow, a pig, a sheep, a goat, a dog, a cat, a horse, and/or a donkey.
4. A method comprising administering the pharmaceutical composition as defined in claim 1 to an animal.
5. A method of controlling parasitic invertebrate pests in or on an animal comprising administering an effective amount of the pharmaceutical composition as defined in claim 1 to the animal.
6. A method according to claim 5, wherein said administration is oral administration, parenteral administration or external administration.
7. A method of controlling parasitic invertebrate pests comprising administering an effective amount of the pharmaceutical composition as defined in claim 1 to the environment in which an animal resides.
8. A pharmaceutical composition comprising component A and component B and a pharmaceutically suitable excipient wherein the component A is at least one compound of formula (I) of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and the component B is a further therapeutic agent.
9. A composition according to of claim 8, wherein component B is imidacloprid, enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, fipronil, ivermectin, omeprazole, tiamulin, benazepril, milbemycin, cyromazine, thiamethoxam, pyriprole, deltamethrin, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, metaflumizone, moxidectin, methoprene (including S-methoprene), clorsulon, pyrantel, amitraz,
triclabendazole, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, fipronil, lufenuron, ecdysone or tebufenozide.
10. A composition according to claim 8, wherein component B is enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, moxidectin, clorsulon, pyrantel, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, lufenuron or ecdysone.
11. A composition according to claim 8, wherein component B is enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, moxidectin, clorsulon or pyrantel.
12. Use of a compound of formula (I) of the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M)and/or, embodiment (N) or a specific compound listed in the embodiment (A), embodiment (B), embodiment (C), embodiment (D), embodiment (E), embodiment (F), embodiment (G), embodiment (H), embodiment (I), embodiment (J), embodiment (K), embodiment (L), embodiment (M) and/or, embodiment (N) against parasitic invertebrate pests in or on an animal or in or on a human.
PCT/EP2012/076538 2011-12-21 2012-12-21 Use of aminobenzamide derivatives for controlling animal parasites WO2013092942A1 (en)

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