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WO2014001121A1 - Isothiazole derivatives as insecticidal compounds - Google Patents

Isothiazole derivatives as insecticidal compounds Download PDF

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Publication number
WO2014001121A1
WO2014001121A1 PCT/EP2013/062513 EP2013062513W WO2014001121A1 WO 2014001121 A1 WO2014001121 A1 WO 2014001121A1 EP 2013062513 W EP2013062513 W EP 2013062513W WO 2014001121 A1 WO2014001121 A1 WO 2014001121A1
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substituted
compounds
formula
alkylcarbonyl
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PCT/EP2013/062513
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French (fr)
Inventor
Myriem El Qacemi
Jérôme Yves CASSAYRE
Guillaume Berthon
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Syngenta Participations Ag
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Publication of WO2014001121A1 publication Critical patent/WO2014001121A1/en

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    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/18—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, directly attached to a heterocyclic or cycloaliphatic ring
    • 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
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
    • C07C323/43—Y being a hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

Definitions

  • the present invention relates to certain isothiazoline derivatives, to processes and intermediates for preparing these derivatives, to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising these derivatives and to methods of using these derivatives to control insect, acarine, nematode and mollusc pests.
  • isoxazoline derivatives with insecticidal properties are disclosed, for example, in EP 1,731,512.
  • new biologically active compounds as well as new biologically active compounds displaying superior properties for use as agrochemical active ingredients, for example greater biological activity, different spectrum of activity, increased safety profile, or increased biodegradability.
  • a 1 , A 2 , and A 3 are independently of each other C-H, C-R 7 , or nitrogen;
  • X 1 represents a two- to four-membered bridge containing carbon atoms as bridge members, optionally containing one or more double bonds, and each bridge member is optionally substituted by one or two R 6 ;
  • R 1 is Ci-Cghaloalkyl
  • R 2 is aryl or aryl substituted by one to five R 11 , or heteroaryl or heteroaryl substituted by one to five R 11 ;
  • R 3 is hydrogen, or C r Ci 2 alkyl substituted by one to five R 8 , C 3 -C 8 cycloalkyl or C 3 - Cgcycloalkyl substituted by one to five R 9 , C 2 -Ci 2 alkenyl or C 2 -Ci 2 alkenyl substituted by one to five R 8 , C 2 -Ci 2 alkynyl or C 2 -Ci 2 alkynyl substituted by one to five R 8 , cyano, Ci_Ci 2 alkoxycarbonyl or Ci_
  • Ci 2 alkoxycarbonyl substituted by one to five R 8 Ci-Ci 2 alkoxythiocarbonyl or Ci-Ci 2 alkoxythiocarbonyl substituted by one to five R 8 ;
  • R 4 is hydrogen, NH 2 , hydroxyl, C 1 -C 12 alkoxy or Ci-Ci 2 alkoxy substituted by one to five R 8 , d- Ci 2 alkylcarbonylamino or Ci-Ci 2 alkylcarbonylamino wherein the alkyl is substituted by one to five R 8 , Ci-Ci 2 alkylamino or Ci-Ci 2 alkylamino wherein the alkyl is substituted by one to five R 8 , Ci-Ci 2 alkyl or Ci-Ci 2 alkyl substituted by one to five R 8 , C 3 -C 8 cycloalkyl or C 3 -C 8 cycloalkyl substituted by one to five R 9 , cyano, C 2 -Ci 2 alkenyl or C 2 -Ci 2 alkenyl substituted by one to five R 8 , C 2 -Ci 2 alkynyl or C 2 -Ci 2 alkynyl substituted by one to five
  • R 5 is hydrogen, cyano, carbonyl, thiocarbonyl, d-C ⁇ alkylcarbonyl or C 1 -C 12 alkylcarbonyl substituted by one to five R 8 , or Ci-Cnalkylthiocarbonyl substituted by one to five R 8 , Ci-Ci 2 alkylaminocarbonyl or Ci-Cnalkylaminocarbonyl wherein the alkyl is substituted by one to five R 8 , Ci-Ci 2 alkylaminothiocarbonyl or wherein the alkyl is substituted by one to five R 8 , C 2 -C24 (total carbon number) dialkylaminocarbonyl or C 2 -C24 (total carbon number) dialkylaminocarbonyl wherein one or both alkyl is substituted by one to five R 8 , C 2 -C 2 4 (total carbon number) dialkylaminothiocarbonyl or C 2 -C 2 4 (total carbon number) dialkylamin
  • R 4 and R 5 together with the nitrogen atom to which they are bound, form a 3- to 6-membered heterocyclic ring which may be substituted by one to five R 14 , or may be substituted with a keto, thioketo or nitroimino group;
  • each R 6 is independently hydrogen, halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, C 2 - Cgalkenyl, C 2 -C 8 haloalkenyl, C 2 -Cgalkynyl, C 2 -Cghaloalkynyl, hydroxy, CpCgalkoxy, CpCghaloalkoxy, mercapto, Ci-C 8 alkylthio, Ci-Cghaloalkylthio, CpCgalkylsulfinyl, CpCghaloalkylsulfinyl, C r Cgalkylsulfonyl, CpCghaloalkylsulfonyl, CpCgalkylcarbonyl, Ci-Cgalkoxycarbonyl, aryl or aryl substituted by one to five R 12 , or heterocyclyl or heterocyclyl substituted by one to five R 12 ;
  • each R 8 is independently halogen, cyano, nitro, hydroxy, NH 2 , mercapto, CpCgalkyl, Q- Cghaloalkyl, C3-Cgcycloalkyl, Q-Cgalkoxy, Ci-Cghaloalkoxy, Ci-Cgalkylthio, Ci-Cghaloalkylthio, Cp Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, Ci-Cgalkylsulfonyl, Ci-Cghaloalkylsulfonyl, Ci-Cgalkylamino, C 2 -Cgdialkylamino, C3-Cgcycloalkylamino, CpCgalkylcarbonyl, Ci-Cgalkoxycarbonyl, d-
  • each R 9 is independently halogen, cyano or Q-Cgalkyl
  • each R 10 is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, C 2 -C 8 alkenyl, C 2 - Cghaloalkenyl, C 2 -C 8 alkynyl, C 2 -C 8 haloalkynyl, hydroxy, Q-Cgalkoxy, Ci-Cghaloalkoxy, mercapto, Ci- Cgalkylthio, CpCghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, CpCgalkylsulfonyl, C r Cghaloalkylsulfonyl, CpCgalkylcarbonyl, Ci -Cgalkoxycarbonyl, aryl or aryl substituted by one to five R 12 , or heterocyclyl or heterocyclyl substituted by one to five R 12 ;
  • each R 11 is independently hydrogen, halogen, cyano, nitro, Q-Cgalkyl, Ci-Cghaloalkyl, C 2 - Cgalkenyl, C 2 -Cghaloalkenyl, C 2 -Cgalkynyl, C 2 -Cghaloalkynyl, hydroxy, Ci-Cgalkoxy, Ci-Cghaloalkoxy, mercapto, Ci-Cgalkylthio, Ci-Cghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, C r
  • each R 12 is independently halogen, cyano, nitro, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy-, or C r C 4 haloalkoxy-;
  • R 13 is aryl or aryl substituted by one to five R 10 , heterocyclyl or heterocyclyl substituted by one to five R 10 ;
  • each R 14 is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, Q-Cgalkoxy, C r Cghaloalkoxy or Ci-Cgalkoxycarbonyl;
  • the compounds of formula (I) may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. The invention also covers salts and N-oxides.
  • the compounds of the invention may contain one or more asymmetric carbon atoms, for example, at the -CR'R 2 - group, and may exist as enantiomers (or as pairs of diastereoisomers) or as mixtures of such.
  • Alkyl groups can be in the form of a straight or branched chain and are, for example, methyl, ethyl, propyl, prop-2-yl, butyl, but-2-yl, 2 -methyl-prop -1 -yl or 2-methyl-prop-2- yl.
  • the alkyl groups are preferably Ci-Ce, more preferably C -C4, most preferably C 1 -C3 alkyl groups. Where an alkyl moiety is said to be substituted, the alkyl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
  • Alkylene groups can be in the form of a straight or branched chain and are, for example, -CH 2 -
  • alkylene groups are preferably C 1 -C3, more preferably C 1 -C 2 , most preferably Ci alkylene groups.
  • Alkenyl groups can be in the form of straight or branched chains, and can be, where appropriate, of either the (E)- or (Z)-configuration. Examples are vinyl and allyl.
  • the alkenyl groups are preferably C 2 -C6, more preferably C 2 -C4, most preferably C 2 -C3 alkenyl groups.
  • Alkynyl groups can be in the form of straight or branched chains. Examples are ethynyl and propargyl.
  • the alkynyl groups are preferably C 2 -C 6 , more preferably C 2 -C 4 , most preferably C 2 -C 3 alkynyl groups.
  • Halogen is fluorine, chlorine, bromine or iodine.
  • Haloalkyl groups are alkyl groups which are substituted by one or more of the same or different halogen atoms and are, for example, difluoromethyl, trifluoromethyl,
  • Haloalkenyl groups are alkenyl groups which are substituted by one or more of the same or different halogen atoms and are, for example, 2,2-difluoro-vinyl or 1 ,2-dichloro-2-fluoro-vinyl.
  • Haloalkynyl groups are alkynyl groups which are substituted by one or more of the same or different halogen atoms and are, for example, l -chloro-prop-2-ynyl.
  • Cycloalkyl groups or carbocyclic rings can be in mono- or bi-cyclic form and are, for example, cyclopropyl, cyclobutyl, cyclohexyl and bicyclo[2.2.1 ]heptan-2-yl.
  • the cycloalkyl groups are preferably C 3 -C 8 , more preferably C 3 -C 6 cycloalkyl groups.
  • the cycloalkyl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
  • Aryl groups are aromatic ring systems which can be in mono-, bi- or tricyclic form. Examples of such rings include phenyl, naphthyl, anthracenyl, indenyl or phenanthrenyl. Preferred aryl groups are phenyl and naphthyl, phenyl being most preferred. Where an aryl moiety is said to be substituted, the aryl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
  • Heteroaryl groups are aromatic ring systems containing at least one heteroatom and consisting either of a single ring or of two or more fused rings.
  • single rings will contain up to three heteroatoms and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulfur.
  • monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (e.g.
  • bicyclic groups include purinyl, quinolinyl, cinnolinyl, quinoxalinyl, indolyl, indazolyl, benzimidazolyl, benzothiophenyl and benzothiazolyl.
  • Monocyclic heteroaryl groups are preferred, pyridyl being most preferred. Where a heteroaryl moiety is said to be substituted, the heteroaryl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
  • Heterocyclyl groups or heterocyclic rings are defined to include heteroaryl groups and in addition their unsaturated or partially unsaturated analogues.
  • monocyclic groups include isoxazolyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, [l,3]dioxolanyl, piperidinyl, piperazinyl, [l,4]dioxanyl, and morpholinyl or their oxidised versions such as 1 -oxo-thietanyl and 1,1-dioxo-thietanyl.
  • bicyclic groups examples include 2,3-dihydro-benzofuranyl, benzo[l,4]dioxolanyl, benzo[l,3]dioxolanyl, chromenyl, and 2,3- dihydro-benzo[l,4]dioxinyl.
  • a heterocyclyl moiety is said to be substituted, the heterocyclyl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
  • Preferred values of A 1 , A 2 , A 3 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 are, in any combination, as set out below.
  • a 1 , A 2 , and A 3 are nitrogen, more preferably no more than two of
  • a 1 , A2 and A 3 are nitrogen and A 2 and A 3 are not both nitrogen. Even more preferably A 1 , A2 and A3 are independently C-H or nitrogen, wherein no more than two of A 1 , A 2 and A 3 are nitrogen, and A 2 and A 3 are not both nitrogen. Yet even more preferably, A 1 is C-H, and A 2 and A 3 are both C-H or one of A 2 and A 3 is C-H and the other is nitrogen.
  • a 1 is C-H or C-R 7 , most preferably A 1 is C-H.
  • a 2 is C-H or C-R 7 , most preferably A 2 is C-H.
  • a 3 is C-H or C-R 7 , most preferably A 3 is C-H.
  • a 1 , A 2 and A 3 are each C-H.
  • R 1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl, more preferably chlorodifluoromethyl or trifluoromethyl, most preferably trifluoromethyl.
  • R 2 is aryl or aryl substituted by one to three R 11 , more preferably R 2 is phenyl or phenyl substituted by one to three R 11 , pyridyl or pyridyl substituted by one to three R 11 , more preferably R 2 is phenyl substituted by one to three R 11 or pyridyl substitued by one to three R 11 , more preferably R 2 is group P
  • X is N or C-R , preferably X is C-R .
  • R 2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4-chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro-5-fluorophenyl-, 3- chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3 ,5 -bis(trifluoromethyl)phenyl-, 3 -(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyr
  • R 3 is hydrogen, d-Cgcycloalkyl, d-Cghalocycloalkyl, C 2 -Ci 2 alkenyl or C 2 -Ci 2 haloalkenyl, C 2 -Ci 2 alkynyl, C 2 -Ci 2 haloalkynyl cyano, Ci_ Ci 2 haloalkoxycarbonyl,
  • R 3 is hydrogen, halogen, cyano, Ci-C 4 alkyl, Ci-C 4 haloalkyl, , more preferably R 3 is hydrogen, halogen, cyano, Ci-C 4 alkyl, Ci-C 4 haloalkyl or C3-C6 cycloalkyl.
  • R 3 is hydrogen, halogen, cyano, Ci-C 4 alkyl, Ci-C 4 haloalkyl or C3-C6 cycloalkyl, most preferably, hydrogen, methyl, ethyl or cyclopropyl.
  • R 4 is hydrogen, NH 2 , hydroxyl, d- Ci 2 alkylcarbonylamino, Cp d-Cgcycloalkyl, d-Cgh
  • R 4 is hydrogen, d-Cgalkyl, d- Cghaloalkyl, d-Cgalkoxy, CpCghaloalkoxy, Ci-Cgalkylcarbonyl, d-Cghaloalkylcarbonyl, d- Cgalkoxycarbonyl, or Ci-Cghaloalkoxycarbonyl. Even more preferably R 4 is hydrogen, Ci-C 4 alkyl or d- dhaloalkyl, most preferably hydrogen.
  • R 5 is hydrogen, cyano, carbonyl, thiocarbonyl, d-d 2 alkylcarbonyl, d- d 2 haloalkylcarbonyl, C 1 -C 12 alkylthiocarbonyl, d -C i 2 haloalkylthiocarbonyl, C 1 -C ⁇ alkylaminocarbonyl, Ci-Ci 2 alkylaminothiocarbonyl, C 2 - C 2 4 (total carbon number) dialkylaminocarbonyl, C 2 -C 2 4 (total carbon number) dialkylaminothiocarbonyl, d-d 2 alkoxyaminocarbonyl, Ci-Ci 2 alkoxyaminothiocarbonyl, Ci-Ci 2 alkoxycarbonyl, Ci- Cghaloalkoxycarbonyl, Ci-Ci 2 alkoxythiocarbonyl, Cp Ci 2 thioalkoxycarbonyl, C 3 - Ci 2
  • R 5 is Ci-Cnhaloalkylcarbonyl
  • Ci-Ci 2 haloalkylthiocarbonyl Ci-Ci 2 alkylaminocarbonyl, Ci-Ci 2 alkylaminothiocarbonyl, C 2 -C 2 4 (total carbon number) dialkylaminocarbonyl, C 2 -C 2 4 (total carbon number) dialkylaminothiocarbonyl, Q- Ci 2 alkoxyaminocarbon
  • Ci 2 thioalkoxycarbonyl C 3 - Ci 2 cycloalkylcarbonyl, C 3 -Ci 2 halocycloalkylcarbonyl, C 2 -Ci 2 alkenylcarbonyl, C 2 - Ci 2 haloalkenylcarbonyl, C 2 -Ci 2 alkynylcarbonyl, C 2 -Ci 2 haloalkynylcarbonyl, C 3 -Ci 2 cycloalkyl-Ci- Ci 2 alkylcarbonyl, C 3 -Ci 2 halocycloalkyl-Ci-Ci 2 alkylcarbonyl, C 2 -Ci 2 alkylsulfenyl-Ci-Ci 2 alkylcarbonyl, Ci-Ci 2 haloalkylsulfenyl-Ci-Ci 2 alkylcarbonyl, Ci-C ⁇ alkylsulfinyl-Ci-C ⁇ alkylcarbonyl
  • Ci 2 alkenylaminocarbonyl, C 2 -Ci 2 alkynylaminocarbonyl or or C( 0)R 13 wherein R 13 is phenyl or phenyl substituted by one to five R 14 , or pyridyl or pyridyl substituted by one to four R 14 .
  • R 5 is CpCnhaloalkylcarbonyl, C 3 - Ci 2 cycloalkylcarbonyl, C 3 -Ci 2 halocycloalkylcarbonyl, C 3 -Ci 2 cycloalkyl-Ci-Ci 2 alkylcarbonyl, C 3 - Ci 2 halocycloalkyl-Ci-Ci 2 alkylcarbonyl, CpC ⁇ alkylsulfenyl-Ci-C ⁇ alkylcarbonyl, C r
  • Ci 2 haloalkylsulfinyl-C 1 -C C 1 - Ci 2 haloalkylsulfonyl-Ci-Ci 2 alkylcarbonyl, C3-Ci 2 cycloalkylaminocarbonyl, or C( 0)R 13 wherein R 13 is phenyl or phenyl substituted by one to five R 14 , or pyridyl or pyridyl substituted by one to four R 14 .
  • R 5 is Ci-Cgalkylcarbonyl, Ci-Cghaloalkylcarbonyl, d-C ⁇ alkoxycarbonyl, C3- Cgcycloalkylcarbonyl, C3-Cghalocycloalkylcarbonyl, C3-Cgcycloalkyl-CH 2 -carbonyl, C3- Cghalocycloalkyl-CH 2 -carbonyl, Ci-Cgalkylsulfenyl-CH 2 -carbonyl, Ci-Cghaloalkylsulfenyl-CH 2 -carbonyl, Ci-Cgalkylsulfinyl-CH 2 -alkylcarbonyl, Ci-Cghaloalkylsulfinyl-CH 2 -carbonyl, Ci-Cgalkylsulfonyl-CH 2 - alkylcarbonyl, or Ci-Cghaloalkylsulfonyl-CH 2 — carbonyl, Ci-Cgal
  • R 13 is phenyl or phenyl substituted by one to five R 14 , or pyridyl or pyridyl substituted by one to four R 14 .
  • R 5 is hydrogen, cyano, carbonyl, thiocarbonyl, d-C ⁇ alkylcarbonyl,
  • Ci-Ci 2 thioalkoxycarbonyl Ci-Ci 2 thioalkoxythiocarbonyl
  • Ci 2 haloalkylsulfenyl-CH 2 -carbonyl Ci-Ci 2 alkylsulfinyl-CH 2 -carbonyl, Ci-Ci 2 haloalkylsulfinyl-CH 2 - carbonyl, Ci-Ci 2 alkylsulfonyl-CH 2 -carbonyl, Ci-Ci 2 haloalkylsulfonyl-CH 2 -carbonyl, Q- Ci 2 alkylcarbonyl-CH 2 -carbonyl, Ci-Ci 2 haloalkylcarbonyl-CH 2 -carbonyl, C 3 -Ci 2 cycloalkylaminocarbonyl, C 2 -Ci 2 alkenylaminocarbonyl, C 2 -Ci 2 alkynylaminocarbonyl.
  • R 4 and R 5 together with the nitrogen atom to which they are bound form a ring, preferably it is a 3 - to 6-membered heterocyclic ring which may be substituted by one to five R 14 , or may be substituted with a keto, thioketo or nitroimino group.
  • R 15 is methyl, ethyl, cyclopropyl, cyclopropylmethyl, 2,2,2-trifluoroethyl, 2-methoxyethyl, methylthiomethyl, methylsulfinylmethyl, methylsulfonylmethyl, methylamino, ethylamino, 2,2,2-trifluoroethylamino, cyclopropylamino, cyclopropylmethylamino, 2,4,6-trifluorophenyl or pyridylmethyl; most preferably R 15 is methyl, ethyl, 2,2,2-trifluoroethyl or cyclopropyl.
  • each R 8 is independently halogen, cyano, nitro, hydroxy, Ci-Cgalkoxy, d- Cghaloalkoxy, Ci-Cgalkylcarbonyl, d-Cgalkoxycarbonyl, mercapto, Ci-Cgalkylthio, Ci-Cghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, CpCgalkylsulfonyl.
  • each R 8 is independently halogen, cyano, nitro, hydroxy, Q-Cgalkoxy, Q-Cghaloalkoxy, mercapto, CpCgalkylthio, Q- Cghaloalkylthio, more preferably bromo, chloro, fluoro, methoxy, or methylthio, most preferably chloro, fluoro, or methoxy.
  • each R 9 is independently cyano, chloro, fluoro or methyl, most preferably each R 9 is methyl.
  • each R 10 is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, d- Cgalkoxy, Ci-Cghaloalkoxy, more preferably bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy, most preferably bromo, chloro, fluoro, cyano or methyl.
  • each R 11 is independently hydrogen, halogen, cyano, nitro, Q-Cgalkyl, Ci-Cghaloalkyl,
  • Q-Cgalkoxy, Ci-Cghaloalkoxy more preferably hydrogen, iodo, bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy, even more preferably hydorgen, bromo, chloro, fluoro, iodo or trifluoromethyl, most preferably hydrogen, bromo, chloro, fluoro or trifluoromethyl.
  • each R 12 is independently bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy, more preferably bromo, chloro, fluoro, nitro or methyl, most preferably each R 12 is independently chloro, fluoro or methyl.
  • R 13 is phenyl or phenyl substituted by one to five R 14 , or pyridyl or pyridyl substituted by one to five R 14 .
  • each R 14 is independently bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy, more preferably bromo, chloro, fluoro, nitro or methyl, more preferably each R 14 is independently chloro, fluoro or methyl.
  • the present invention provides compounds of formula (I) (embodiment A) wherein A 1 is C-H, or nitrogen, A 2 and A 3 are independently C-H or nitrogen, wherein no more than two of A 1 , A 2 and A 3 are nitrogen, and A 2 and A 3 are not both nitrogen;
  • R 1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl
  • R 2 is group P
  • X 2 is N or C-R 11 ;
  • R 3 is hydrogen, methyl, ethyl or cyclopropyl
  • R 4 is hydrogen, Ci-C 4 alkyl or Ci-C 4 haloalkyl
  • R 15 is C r C 4 alkyl, C r C 4 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl-Ci-C 4 alkyl,
  • Ci-C 4 alkoxy Ci-C 4 alkoxy-Ci-C 4 alkyl, Ci-C 4 haloalkoxy-Ci-C 4 alkyl, C 1 -C4 alkylthio-Ci-C 4 alkyl, Ci-C 4 alkylsulfinyl-Ci-C 4 alkyl, Ci-C 4 alkylsulfonyl-Ci-C 4 alkyl, Ci-C 4 alkylamino, d- C 4 haloalkylamino, Cs-Cgcycloalkylamino, phenyl optionally substituted by halogen or pyridylmethyl.
  • X 1 is as defined for the compound of formula I, but preferably represents
  • the present invention provides compounds of formula (I) (embodiment B) wherein A 2 , A 3 and A 4 are C-H and X 1 , R 1 , R 2 , R 3 , R 4 and R 5 are as defined for compounds of formula (I); or a salt or N-oxide thereof.
  • the preferences for X 1 , R 1 , R 2 , R 3 , R 4 and R 5 are the same as the preferences set out for the corresponding substituents of compounds of the formula (I).
  • X 1 preferably represents -C(R 6 )(R 6 )-C(R 6 )(R 6 )- or
  • a , A and A are independently C-H or nitrogen, wherein no more than two of A , A and A are nitrogen, and A 2 and A 3 are not both nitrogen;
  • R 1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl
  • R 2 is group P
  • X 2 is C or N, and X 1 , R 3 , R 4 , R 5 , and R 1 1 are as defined for compounds of formula I; or a salt or N-oxide thereof.
  • the preferences for A 1 , A 2 , A 3 , X'R 1 , R 2 , R 3 , R 4 , R 5 , and R 1 1 are the same as the preferences set out for the corresponding substituents of compounds of the formula (I).
  • X 1 preferably represents -C(R 6 )(R 6 )-C(R 6 )(R 6 )- or -C(R 6 )(R 6 )-C(R 6 )(R 6 )-C(R 6 )(R 6 )-, more
  • X 1 preferably represents -C(R 6 )(R 6 )-C(R 6 )(R 6 )- or -C(R 6 )(R 6 )-C(R 6 )(R 6 )-C(R 6 )(R 6 )-, more
  • R 4 is preferably hydrogen
  • R 15 is preferably methyl, ethyl, cyclopropyl, cyclopropylmethyl, 2,2,2-trifluoroethyl, 2-methoxyethyl, methylthiomethyl
  • X 1 preferably represents -C(R 6 )(R 6 )-C(R 6 )(R 6 )- or -C(R 6 )(R 6 )-C(R 6 )(R 6 )-C(R 6 )(R 6 )-, more
  • a 1 , A 2 , A 3 , R 1 , R 2 , R 4 , R 5 and R 6 and preferences thereof are as defined for compounds of formula I and n is 0 to 4.
  • A,A,A,R,R,R,R and R and preferences thereof are as defined for compounds of formula I and n is 0 to 5.
  • a , A, A X 1 , R , R , and R J are as defined for compounds of fomula I, or a salt of N-oxide
  • a , A, A X 1 , R , R", R ⁇ R and R J are as defined for compounds of fomula I, and R is H, cyano, halogen, CpCgalkyl, Ci-Cgalkylcarbonyl, arylsulfinyl wherein the aryl (preferably phenyl) is optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C 4 alkyl, d- C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy, arylsulfonyl wherein the aryl (preferably phenyl) is optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C 4 alkyl, d- C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy, benzyl optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C
  • R is preferably hydrogen, methylcarbonyl, benzyl or butyl (preferably tbutyl).
  • Table 1 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 2 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 3 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 4 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 5 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 6 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-fluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 7 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 8 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is CH, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 9 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 10 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -bromophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 11 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 12 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 13 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 14 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 15 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 16 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 17 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 18 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 19 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 20 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 21 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 22 is a compound of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 22 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 23 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 24 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 25 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 26 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 27 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 28 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 29 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 30 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 31 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 32 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 33 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl
  • Al is N
  • A2 is CH
  • A3 is CH
  • Rl, Ga and Gb are as defined in Table P.
  • Table 34 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 35 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 36 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 37 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 38 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 39 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 40 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 41 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 42 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 43 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 44 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 45 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 46 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 47 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 48 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 49 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 50 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 51 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl
  • Al is CH
  • A2 is N
  • A3 is CH
  • Rl, Ga and Gb are as defined in Table P.
  • Table 52 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 53 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 54 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 55 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 56 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 57 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 58 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 59 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 60 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 61 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 62 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 63 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 64 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -bromophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 65 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 66 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 67 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 68 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 69 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 70
  • Table 70 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 71 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 72 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 73 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 74 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 75
  • Table 75 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 76 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 77 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 78 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 79 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 80 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 81 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 82 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 83 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 84 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 85 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 86 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 87 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 88 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 88 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 89 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
  • Table 90 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
  • Table 91 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 92 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 93 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 94 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 95 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 96 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 97 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 98 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 99 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 100 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 101 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-fluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 102 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 103 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 104 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 105 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 106 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 107 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 108 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 109 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 110 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 111 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 112 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 113 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 114 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-fluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 115 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 116 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 117 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 118 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 119 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-fluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 120 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 121 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 122 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 123 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • Table 124 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 125 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
  • Table 126 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
  • R2 is 2,6-bis(trifluoromethyl)-4-pyridyl
  • Al is N
  • A2 is CH
  • A3 is N
  • Rl, Ga and Gb are as defined in Table P.
  • Compounds of formula I include at least one chiral centre and may exist as compounds of formula I* or compounds of formula I**.
  • Compounds I* and I** are enantiomers if there is no other chiral center or epimers otherwise.
  • compounds of formula I** are more biologically active than compounds of formula I*.
  • the invention includes mixtures of compounds I* and I** in any ratio e.g. in a molar ratio of 1 :99 to 99:1, e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio.
  • the molar proportion of compound I** compared to the total amount of both enantiomers is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.
  • the molar proportion of the compound of formula I* compared to the total amount of both enantiomers (or epimerically) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.
  • Enantiomerically (or epimerically) enriched mixtures of formula I** are preferred.
  • Each compound disclosed in Tables 1 to 126 represents a disclosure of a compound according to the compound of formula I* and a compound according to the compound of formula I**.
  • the compounds of the invention may be made by a variety of methods as shown in the following
  • a 1 , A 2 , A 3 , A 4 , X 1 , R 3 , R 4 and R 5 are as defined for compounds of formula I.
  • Compounds of formula (IV) wherein Ar stands for group A or group Al can be prepared by reacting a compound of formula (III) with the vinyl compound of formula (II) optionally in the presence of a suitable solvent, for example NN-dimethylformamide, xylene, toluene, chlorobenzene or
  • Compounds of formula VI may be prepared from compounds of formula V by cleavage of the phthalimide protecting group (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience,New York, 1999, 564-566, 740-743.).
  • Preferred reagents for this transformation are hydrazine or hydrazine hydrate in a suitable solvent (methanol, ethanol, tetrahydrofuran, toluene and others).
  • Reaction temperature is in the range 0°C to 200°C, more preferably 25°C to 150°C.
  • the reaction time is usually in the range O.lh to lOOh.
  • Compounds of formula (VIII) can be prepared by reacting a compound of formula (VII) wherein Rx is OH, Ci-Cealkoxy or CI, F or Br, with an amine of formula (VI) as shown in Scheme 3.
  • Rx is OH
  • such reactions are usually carried out in the presence of a coupling reagent, such as ⁇ , ⁇ '- dicyclohexylcarbodiimide (“DCC”), l-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (“EDC”) or bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-C1”)
  • DCC ⁇ , ⁇ '- dicyclohexylcarbodiimide
  • EDC l-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride
  • BOP-C1 bis(2-oxo-3-oxazolid
  • Rx is CI
  • such reactions are usually carried out in the presence of a base, and optionally in the presence of a nucleophilic catalyst. It is possible to conduct the reaction in a biphasic system comprising an organic solvent, preferably ethyl acetate, and an aqueous solvent, preferably a solution of sodium hydrogen carbonate.
  • a base preferably pyridine, triethylamine, 4-(dimethylamino)-pyridine (“DMAP”) or diisopropylethylamine (Hunig's base).
  • Preferred solvents are NN-dimethylacetamide, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, ethyl acetate and toluene.
  • the reaction is carried out at a temperature of from 0°C to 100°C, preferably from 15°C to 30°C, in particular at ambient temperature.
  • C 4 alkylene-or Q-Cgalkylcarbonyl- or arylsulfonyl- or arylthio- can be obtained by reacting an unsaturated ketone of formula (IX), with a sulfur nucleophile, such as thioacetic acid, hydrogen sulfide, sodium sulfide, ammonium sulfide, thiourea, benzylmercaptan, Sodium benzenethiosulfonate, potassium thiocyanate, sodium thiocyanate, sodium thiomethoxide or tert-butyl mercaptan as shown on Scheme 4.
  • a sulfur nucleophile such as thioacetic acid, hydrogen sulfide, sodium sulfide, ammonium sulfide, thiourea, benzylmercaptan, Sodium benzenethiosulfonate, potassium thiocyanate, sodium thiocyanate, sodium thiomethoxide
  • Such reactions can be performed optionally in the presence of a base, such as sodium hydroxide, sodium ethoxide, sodium methoxide, sodium tert-butoxide or potassium hydroxide.
  • a base such as sodium hydroxide, sodium ethoxide, sodium methoxide, sodium tert-butoxide or potassium hydroxide.
  • an acid for example p-toluenesulfonic acid, hydrochloric acid, acetic acid
  • a solvent such as methanol, ethanol, NN-dimethylformamide, toluene, dichloromethane, ethyl acetate, acetonitrile or chlorobenzene or water, or mixtures thereof, at a temperature of from 0°C to
  • Such reactions are usually carried out in the presence of an acid or not, for example p-toluenesulfonic acid, hydrochloric acid, acetic acid, optionnally in the presence of a solvent, for example an alcohol, such as methanol or ethanol, or toluene, dichloromethane, water, or mixtures thereof.
  • a solvent for example an alcohol, such as methanol or ethanol, or toluene, dichloromethane, water, or mixtures thereof.
  • the reaction can be carried out in the presence or the absence of a dehydrating agent, such as anhydrous magnesium sulfate or molecular sieves. It can also be perfomed using a Dean Stark or Soxhlet apparatus that enables a constant removal of the water formed during the reaction.
  • the reaction is carried out at a temperature of from 0°C to 100°C, preferably from 15°C to 30°C, in particular at ambient temperature.
  • Such reactions are carried out in the presence of a base, for example an organic base, such as triethylamine or sodium acetate, or an inorganic base, such as sodium hydrogen carbonate, optionally in the presence of a solvent, for example an alcohol, such as methanol or ethanol, or water, or mixtures thereof.
  • a base for example an organic base, such as triethylamine or sodium acetate, or an inorganic base, such as sodium hydrogen carbonate
  • a solvent for example an alcohol, such as methanol or ethanol, or water, or mixtures thereof.
  • Such reactions can also be carried out in the presence of an acid or not, for example p- toluenesulfonic acid, hydrochloric acid, acetic acid, optionnally in the presence of a solvent, for example an alcohol, such as methanol or ethanol, or toluene, dichloromethane, water, or mixtures thereof.
  • the reaction can be carried out in the presence or the absence of a dehydrating agent, such as anhydrous magnesium sulfate or molecular sieves. It can also be perfomed using a Dean Stark or Soxhlet apparatus that enables a constant removal of the water formed during the reaction.
  • a dehydrating agent such as anhydrous magnesium sulfate or molecular sieves. It can also be perfomed using a Dean Stark or Soxhlet apparatus that enables a constant removal of the water formed during the reaction.
  • the reaction is carried out at a temperature of from 0°C to 100°C, preferably from 15°C to 30°C, in particular at ambient temperature.
  • Compounds of formula (IV) can be obtained by cyclising a compound of formula (X) wherein Z 3 is thiol. Such reactions are usually carried out in the presence of an acid or not, for example p- toluenesulfonic acid, optionnally in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene. The reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C.
  • compounds of formula (IV) can be obtained by cyclising a compound of formula (X) wherein Z 3 is aryl substituted Ci-Cgalkylsulfinyl-. Such reactions are usually carried out in the presence of an acid or not, for example p-toluenesulfonic acid,
  • reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C.
  • a solvent for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene.
  • the reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C.
  • Such reactions usually involve first the deprotection of the thiol to give a compound of formula (X) wherein Z 3 is thiol, followed by the cyclization.
  • Compounds of formula (IV) can be obtained from compound of formula (XIII) from an oxidation step.
  • Such reactions are usually carried out in the presence of an oxidant, for example iodine, bromine, thionyl chloride, Bis(trifluoroacetoxy)iodobenzene;
  • the reaction can be carried out in the presence of an acid or not, such as trifluoroacetic acid or acetic acid, optionnally in the presence of a solvent, for example dichloroethane, dimethylsulfoxide, NN-dimethylformamide, methanol, ethanol, toluene, dichloromethane, ethyl acetate or chlorobenzene.
  • the reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C.
  • compounds of formula (IV) can be obtained directly from a compound of formula (XIV) wherein Z 1 is hydrogen.
  • Such reactions are usually carried out in the presence chloramines, formed in situ from ammonia and chlorine or sodium hypochlorite or hypochlorous acid, optionnally in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene.
  • a solvent for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene.
  • the reaction is carried out at a temperature of from -80°C to 40°C, preferably below - 40°C.
  • compounds of formula (IV) can be obtained directly from a compound of formula (XI) wherein Z 1 is halogen, cyano, arylsulfonyl- or arylthio-.
  • Such reactions are usually carried out in the presence ammonia, optionnally in the presence of a solvent, for example dichloroethane, tetrahydrofuran, ⁇ methanol, ethanol, toluene, dichloromethane or chlorobenzene.
  • a solvent for example dichloroethane, tetrahydrofuran, ⁇ methanol, ethanol, toluene, dichloromethane or chlorobenzene.
  • the reaction is carried out at a temperature of from -80°C to 80°C.
  • compounds of formula (IV) can be obtained directly from a compound of formula (XI) wherein Z 1 is aryl-Ci-C 4 alkylene.
  • Such reactions are usually carried out in two steps- The first one involves the treatment of a compound of formula (XI) wherein Z 1 is aryl-Ci-C 4 alkylene by a suitable oxidant, such as sulfuryl chloride or chlorine, in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene, to provide a compound of formula (XI) wherein Z 1 is chlorine.
  • a suitable oxidant such as sulfuryl chloride or chlorine
  • the second step then involves the treatment a compound of formula (XI) wherein Z 1 is chlorine by an ammonia source, such as ammonia or ammonium bromide in the presence of a base, in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, tetrahydrofuran, dichloromethane or chlorobenzene.
  • an ammonia source such as ammonia or ammonium bromide
  • a base for example dichloroethane, methanol, ethanol, toluene, tetrahydrofuran, dichloromethane or chlorobenzene.
  • a solvent for example dichloroethane, methanol, ethanol, toluene, tetrahydrofuran, dichloromethane or chlorobenzene.
  • compounds of formula (IV) can be obtained directly from a compound of formula (XI) wherein Z 1 is hydrogen.
  • Such reactions are usually carried out in the presence of a suitable nitrogen electrophile, such as Hydroxylamine-O-sulfonic acid.
  • a suitable nitrogen electrophile such as Hydroxylamine-O-sulfonic acid.
  • Such reactions are carried out in the presence of a base, for example an organic base, such as triethylamine or sodium acetate, or an inorganic base, such as sodium hydrogen carbonate, sodium hydroxide or potassium hydroxide optionally in the presence of a solvent, for example tetrahydrofuran, toluene, an alcohol, such as methanol or ethanol, or water, or mixtures thereof.
  • the reaction is carried out at a temperature of from -80°C to 80°C.
  • 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 compounsd of the invention 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.
  • Compositions comprising the compound of formula I may be used on ornamental garden plants (e.g.
  • compositions comprising the compound of formula I may be used on garden plants (e.g. flowers, shrubs, broad-leaved trees or evergreens), on indoor plants (e.g. flowers and shrubs) and on indoor pest e.g. to control aphids, whitefly, scales, meelybug, beetles and caterpillars.
  • the compounds of the invention may be effective against harmful insects, without substantially imposing any harmful side effects to cultivated plants.
  • Application of the compounds of the invention may increase the harvest yields, and may improve the quality of the harvested material.
  • 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.
  • pest species which may be controlled by the compounds of formula (I) include: coleopterans, for example, Callosobruchus chinensis, Sitophilus zeamais, Tribolium castaneum,
  • Epilachna vigintioctomaculata Agriotes fuscicollis, Anomala rufocuprea, Leptinotarsa decemlineata, Diabrotica spp., Monochamus alternatus, Lissorhoptrus oryzophilus, Lyctus bruneus, Aulacophora femoralis; lepidopterans, for example, Lymantria dispar, Malacosoma neustria), Pieris rapae,
  • nematodes for example, Meloidogyne incognita, Bursaphelenchus lignicolus Mamiya et Kiyohara, Aphelenchoides besseyi, Heterodera glycines, Pratylenchus spp..
  • Examples of further pest species which may be controlled by the compounds of formula (I) include: 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., Hyal
  • 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.,
  • 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., Stictoce
  • Hymenoptera for example, Diprion spp., Hoplocampa spp., Lasius spp., Mono- morium pharaonis, Vespa spp.; from the order of the Isopoda, for example, Armadillidium vulgar e, 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 fumifer
  • 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.
  • Symphyla for example, Scutigerella immaculata
  • Thysanoptera for example, Basothrips biformis, Enneothrips flavens, Frankliniella spp., Heliothrips spp., Hercinothrips femoralis, Kakothrips spp., Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp.
  • 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 Tyiphinema spp.
  • the compounds of the invention may be used to control the following pest spcies: 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.
  • 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
  • Kalotermitidae for example Neotermes spp.
  • the Rhinotermitidae for example Coptotermes formosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R. hesperus, and R. santonensis
  • 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 eelworm Trichostrongylus spp.
  • Trichostrongylus spp. gastro intestinal nematodes
  • Deroceras reticulatum slug
  • the compound of formula I 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.
  • citrus e.g. in some cases 60-200g/ha
  • almonds e.g. in some cases 40-180g/ha
  • fruiting vegetables cucurbits and pulses (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.
  • grapes e.g. in some cases 30-180g/ha
  • pome fruit e.g. apples, pears etc.
  • stone fruit e.g. pears, plums etc.
  • the compounds of the invention may be used for pest control on various plants, including soybean, corn, sugarcane, alfalfa, brassicas, oilseed rape (e.g. canola), potatoes (including sweet potatoes), cotton, rice, coffee, citrus, almonds, fruiting vegetables, cucurbits and pulses (e.g. tomatoes, pepper, chili, eggplant, cucumber, squash etc.), tea, bulb vegetables (e.g. onion, leek etc.), grapes, pome fruit (e.g. apples, pears etc.), stone fruit (e.g. pears, plums etc.), and cereals.
  • the compounds of the invention may be used on soybean to control, for example, Elasmopalpus Ugnosellus, Diloboderus abderus, Diabrotica speciosa, Trialeurodes spp., Bemisia spp., aphids, Sternechus subsignatus, Formicidae, Agrotis ypsilon, Julus spp., Murgantia spp., Halyomorpha spp., Thyanta spp., Megascelis ssp., Procornitermes ssp., Gryllotalpidae, Nezara viridula, Piezodorus spp., Acrosternum spp., Neomegalotomus spp., Cerotoma trifurcata, Popil a japonica, Edessa spp., Liogenys fuscus, Euschistus heros, stalk borer, Scaptocoris castanea, phyll
  • Pseudoplusia includens, Anticarsia gemmatalis, Epinotia spp., Rachiplusia spp., Spodoptera spp., Bemisia tabaci, Tetranychus spp., Agriotes spp. , Euschistus spp..
  • the compounds of the invention are preferably used on soybean to control Diloboderus abderus, Diabrotica speciosa, Trialeurodes spp., Bemisia spp., Nezara viridula, Piezodorus spp., Acrosternum spp., Cerotoma trifurcata, PopilUa japonica, Euschistus heros, Scaptocoris castanea, phyllophaga spp., Migdolus spp., Agriotes spp., Euschistus spp..
  • the compounds of the invention may be used on corn to control, for example, Euschistus heros, Euschistus spp., Dichelops furcatus, Diloboderus abderus, Thyanta spp., Elasmopalpus Ugnosellus, Halyomorpha spp., Spodoptera frugiperda, Nezara viridula, Cerotoma trifurcata, PopilUa japonica, Agrotis ypsilon, Diabrotica speciosa, aphids, Heteroptera, Procornitermes spp., Scaptocoris castanea, Formicidae, Julus ssp., Dalbulus maidis, Diabrotica virgifera, Diabrotica spp., Mods latipes, Bemisia tabaci, heliothis spp., Tetranychus spp., thrips spp., phyllophaga spp., Mi
  • Euschistus spp. Dichelops furcatus, Diloboderus abderus, Nezara viridula, Cerotoma trifurcata, PopilUa japonica, Diabrotica speciosa, Diabrotica virgifera, Diabrotica spp., Tetranychus spp., Thrips spp., Phyllophaga spp., Migdolus spp., Scaptocoris spp., Agriotes spp..
  • the compounds of the invention may be used on sugar cane to control, for example,
  • Sphenophorus spp. termites, Migdolus spp., Diloboderus spp., Telchin licus, Diatrea saccharalis, Mahanarva spp., Mealybugs.
  • 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 spp., Geocoris spp., Lygus hesperus, Lygus Uneolaris, Spissistilus spp., Spodoptera spp., Aphids, Trichoplusia ni.
  • the compounds of the invention are preferably used on alfalfa to control Hypera brunneipennis, Hypera postica, Empoasca solana, Epitrix spp., Lygus hesperus, Lygus Uneolaris, 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., - jo -
  • 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, Halotydeus destructor, 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., Aphids, wireworms.
  • 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, Trialeurodes spp., Aphids, Lygus spp., phyllophaga spp., Scaptocoris spp., Austroasca viridigrisea, Creontiades spp., Nezara spp., Piezodorus spp., Halotydeus destructor, Oxycaraenus hyalinipennis, Dysdercus cingulatus.
  • Anthonomus grandis Pectinophora spp., heliothis spp., Spodoptera spp., Tetranychus spp., Empoasca 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, Scotinophara spp., Nephotettix malayanus, Nephotettix nigropictus, Nephotettix parvus, Nephottetix virescens, Nephotettix spp., Mealybugs, Sogatella furcifera, Nilaparvata lugens, Orseolia spp., Cnaphalocrocis medinalis, Marasmia spp., Stenchaetothrips biformis, Thrips spp., Hydrellia philippina, Grasshoppers, Pomacea canaliculata, Scirpophaga innotata
  • the compounds of the invention are preferably used on rice to control Leptocorisa spp., Lissorhoptrus spp., Oebalus pugnax, Nephotettix malayanus, Nephotettix nigropictus, Nephotettix parvus, Nephottetix virescens, Nephotettix spp., Sogatella furcifera, Stenchaetothrips biformis, Thrips spp., Hydrellia philippina, Grasshoppers, Pomacea canaliculata, Scirpophaga innotata, Chilo suppressalis, Chilo polychrysus, Oulema oryzae.
  • the compounds of the invention may be used on coffee to control, for example, Hypothenemus
  • 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., Aphids, Hardscales, Softscales, Mealybugs.
  • 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 vegetables, cucurbits and pulses, 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., Tuta absoluta, Liriomyza spp., Bemisia tabaci, Trialeurodes spp., Aphids, Paratrioza spp., Frankliniella occidentalis , Frankliniella spp., Anthonomus spp., Phyllotreta spp., Amrasca spp., Epilachna spp., Halyomorpha spp., Scirtothrips spp., Leucinodes spp., Neoleucinodes spp.
  • Maruca spp. Fruit flies, Stinkbugs, Lepidopteras, Coleopteras.
  • the compounds of the invention are preferably used on fruiting vegetables, cucurbits and pulses, 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., Paratrioza spp., Frankliniella
  • the compounds of the invention may be used on tea to control, for example, Pseudaulacaspis spp., Empoasca spp., Scirtothrips spp., Caloptilia theivora, Tetranychus spp..T e compounds of the invention are preferably 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. Eupoecilia ambiguella, Frankliniella spp., Thrips spp., Tetranychus spp., Rhipiphorothrips Cruentatus, Eotetranychus Willamettei, Erythroneura Elegantula, Scaphoides spp., Scelodonta strigicollis, Mealybugs.
  • 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, pears etc., to control, for example, Cacopsylla spp., Psylla spp., Panonychus ulmi, Cydia pomonella, Lepidopteras, Aphids, Hardscales, Softscales.
  • the compounds of the invention are preferably used on pome fruit, including apples, pears 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., Aphids, Hardscales, Softscales, Mealybugs.
  • the compounds of the invention are preferably used on stone fruit to control Scirtothrips spp., Thrips spp., Frankliniella spp., Tetranychus spp..
  • the compounds of the invention may be used on cereals to control, for example, Aphids, Stinkbugs, earthmites, Eurygaster integriceps, Zabrus tenebrioides, Anisoplia austriaca, Chaetocnema aridula, Phyllotreta spp., Oulema melanopus, Oscinella spp., Delia spp., Mayetiola spp., Contarinia spp., Cephus spp., Steneotarsonemus spp., Apamea spp..
  • compounds of formula I may be used on rice to control Beautyothrips biformis (Thrips), Chilo spp. (e.g. Chilo polychrysus (Dark headed striped borer), Chilo suppressalis 4Q
  • Laodelphax striatellus Laodelphax striatellus ), Lema oryzae (Rice leaf eetle), Leptocorsia acuta (Rice bug), Leptocorsia oratorius (rice bug), Lissorhoptrus oryzophilus (rice water weevil), Mythemina separata (armyworm), Nephottetix spp. (Green leafhopper ) (e.g.
  • Nephotettix cincticeps Nephotettix malayanus, Nephotettix nigropictus, Nephotettix parvus, Nephottetix virescens), Nilaparvata lugens (Brown Planthopper), Nymphula depunctalis (Rice caseworm), Orseolia oryzae (Rice Gall midge), Oulema oryzae (Rice leafbeetle), Scirpophaga incertulas (Yellow Stemborer), Scirpophaga innotata (White Stemborer), Scotinophara coarctata (Rice black bug), Sogaella frucifera (White-backed planthopper),
  • 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 web worms, 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,
  • 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.
  • Ants including Imported fire ants, Armyworms, Centipedes, Crickets, Cutworms, Earwigs, Fleas (adult), Grasshoppers, Japanese beetles (adult), Millipedes, Mites, Mosquit
  • the compounds of formula (I) may be used for soil applications, including as a seed application, to target at least the following: sucking pests such as aphids, thrips, brown plant hopper (e.g. on rice), sting bugs, white flies (e.g. on cotton and vegetables), mites; on soil pests such as corn root worm, wireworms, white grubs, zabrus, termites (e.g. on sugar cane, soy, pasture), maggots, cabbage root fly, red legged earth mite; on lepidoptera, such as spodoptera, cutworms, elasmoplpus , plutella (e.g.
  • brassica stem borers, leaf miners, flea beetle, Sternechus; on nematicides, such as Heterodera glycines (e.g. on soybean), Pratylenchus brachyurus (e.g. on corn), P. zeae (e.g. oncorn), P. penetrans (e.g. on corn), Meloidogyne incognita (e.g. on vegetables), Heterodera schachtii (e.g. on sugar beet), Rotylenchus reniformis (e.g. on cotton), Heterodera avenae (e.g. on cereals), Pratylenchus neglectus (e.g. on cereals), thornei (e.g. on cereals).
  • Heterodera glycines e.g. on soybean
  • Pratylenchus brachyurus e.g. on corn
  • P. zeae e.g.
  • the compounds of formula (I) may be used for seed applications at least on the following: soil grubs for corn, soybeans, sugarcane: Migdolus spp; Phyllophaga spp.; Diloboderus spp; Cyclocephala spp; Lyogenys fuscus; sugarcane weevils: Sphenophorus levis & Metamasius hemipterus; termites for soybeans, sugarcane, pasture, others: Heterotermes tenuis; Heterotermes longiceps; Cornitermes cumulans; Procornitermes triacifer ; Neocapritermes opacus; Neocapritermes parvus; corn root worms for corn and potatoes: Diabrotica spp., seed Maggot: Delia platura; soil stinkbugs: Scaptocoris castanea; wireworms: Agriotes spp; Athous spp Hipnodes bicolor; Ctenicera destructor; Limonius canu; Limonius cali
  • 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).
  • an animal pest e.g. an invertebrate animal pest
  • 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).
  • the invention provides a method of combating and/or 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,
  • the compounds of formula (I) are preferably used against insects, acarines or nematodes.
  • plants 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.
  • herbicides or classes of herbicides e.g. ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors
  • 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
  • Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaf, flower and root, examples which may be mentioned being leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes.
  • the plant parts also include harvested material, and vegetative and generative propagation material, for example cuttings, tubers, rhizomes, offshoots and seeds.
  • Treatment according to the invention of the plants and plant parts with the active compounds is carried out directly or by allowing the compounds to act on their surroundings, habitat or storage space by the customary treatment methods, for example by immersion, spraying, evaporation, fogging, scattering, painting on, injecting and, in the case of propagation material, in particular in the case of seed, also by applying one or more coats.
  • Compounds of formula I may be used on transgenic plants (including cultivars) obtained by genetic engineering methods and/or by conventional methods. These are understood as meaning plants having novel properties ("traits") which have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. Depending on the plant species or plant cultivars, their location and growth conditions (soils, climate, vegetation period, diet), the treatment according to the invention may also result in superadditive "synergistic") effects.
  • the preferred transgenic plants or plant cultivars which are to be treated according to the invention include all plants which, by virtue of the genetic modification, received genetic material which imparts particularly advantageous, useful traits to these plants. Examples of such traits are better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, higher quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products.
  • transgenic plants which may be mentioned are the important crop plants, such as cereals (wheat, rice), maize, soybean, potatoes, sugar beet, tomatoes, peas and other vegetable varieties, cotton, tobacco, oilseed rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes).
  • Pesticidal proteins may be used on transgenic plants that are capable of producing one or more pesticidal proteins which confer upon the transgenic plant tolerance or resistance to harmful pests, e.g. insect pests, nematode pests and the like.
  • pesticidal proteins include, without limitation, Cry proteins from Bacillus thuringiensis CrylAb, CrylAc, CrylF, Cry2Ab, Cry2Ae, Cry3A, Cry3Bb, or Cry9C; engineered proteins such as modified Cry3A ( US Patent 7,030,295) or CrylA.105; or vegetative insecticidal proteins such as Vipl, Vip2 or Vip3.
  • Bt Cry proteins and VIPs useful in the invention can be found on the worldwide web at Bacillus thuringiensis Toxin Nomenclature Database maintained by the University of Wales ⁇ see also, Crickmore et al. (1998) Microbiol. Mol. Biol. Rev. 62:807-813).
  • Other pesticidal proteins useful in the invention include proteins of bacteria colonizing nematodes, e.g. Photorhabdus spp.
  • toxins produced by animals such as scorpion ⁇ toxins, arachnid toxins, wasp toxins, or other insect-specific neurotoxins
  • toxins produced by fungi such Streptomycetes toxins, plant lectins, such as pea or barley lectins; agglutinins
  • proteinase inhibitors such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin or papain inhibitors
  • ribosome- inactivating proteins (RIP) such as ricin, maize-RIP, abrin, luffin, saporin or bryodin
  • steroid metabolism enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-IDP-glycosyl -transferase, cholesterol oxidases, ecdysone inhibitors or HMG-CoA-reductase
  • ion channel blockers such as blockers of sodium
  • pesticidal proteins or transgenic plants capable of synthesizing such proteins are disclosed, e.g., in EP-A 374753, WO 93/007278, WO 95/34656, EP-A 427529, EP-A 451878, WO 03/18810 and WO 03/52073.
  • Agrisure®CB (PI) (corn producing CrylAb), Agrisure®RW (P2) (corn producing mCry3A), Agrisure® Viptera (P3) (corn hybrids producing Vip3Aa); Agrisure300GT (P4) (corn hybrids producing CrylAb and mCry3A); YieldGard® (P5) (corn hybrids producing the CrylAb protein), YieldGard® Plus (P6) (corn hybrids producing CrylAb and Cry3Bbl), Genuity® SmartStax® (P7) (corn hybrids with CrylA.105, Cry2Ab2, CrylF, Cry34/35, Cry3Bb) ; Herculex® I (P8) (corn hybrids producing CrylFa) and Herculex®RW (P9) (corn hybrids producing Cry34Abl, Cry35Abl and the enzyme Phosphinothricin-N-
  • transgenic crops are:
  • Btl 76 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (PI 7). 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 CrylA(b) toxin. Btl 76 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
  • MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (PI 8). Maize which has been rendered insect-resistant by transgenic expression of a modified CrylllA toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-D-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. ⁇
  • MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/DE/02/9 (P19). MON 863 expresses a CrylllB(bl) toxin and has resistance to certain Coleoptera insects.
  • NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren,
  • NK603 ⁇ 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 CrylA(b) toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
  • transgenic plants and of very high interest, are those carrying traits conferring resistance to 2.4D (e.g. Enlist®) (e.g. WO 2011066384) (P23), glyphosate (e.g. Roundup Ready® (P24), Roundup Ready 2 Yield® (P25)), sulfonylurea (e.g. STS®) (P26), glufosinate (e.g.
  • soybean plants carrying trains conferring resistance to 2.4D e.g. Enlist®
  • glyphosate e.g.
  • sulfonylurea e.g. STS®
  • glufosinate e.g. Liberty Link®, Ignite®
  • Dicamba e.g. isoxaflutole herbicide
  • Double or triple stack in soybean plants of any of the traits described here are also of interest, including glyphosate and sulfonyl-urea tolerance (e.g. Optimum GAT®, plants stacked with STS® and Roundup Ready® or Roundup Ready 2 Yield®), dicamba and glyphosate tolerance (Monsanto).
  • 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).
  • compositions both solid and liquid formulations
  • the composition is generally used for the control of pests such that a compound of formula (I) is applied at a rate of from O.lg to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
  • a compound of formula (I) 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 O.OOlg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
  • the present invention provides a composition
  • 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.
  • 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 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.
  • 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
  • Soluble powders 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
  • water-soluble inorganic salts such as sodium bicarbonate, sodium carbonate or magnesium sulfate
  • water-soluble organic solids such as a polysaccharide
  • compositions may also be granulated to form water soluble granules (SG).
  • WP Wettable powders
  • a compound of formula (I) 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
  • Granules 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.
  • a hard core material such as sands, silicates, mineral carbonates, sulfates or phosphates
  • 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).
  • solvents such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters
  • 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).
  • DC Dispersible Concentrates
  • a compound of formula (I) may be prepared by dissolving a compound of formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether.
  • organic solvent such as a ketone, alcohol or glycol ether.
  • surface active agent for example to improve water dilution or prevent crystallization in a spray tank.
  • Emulsifiable concentrates 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 C 8 -Ci 0 fatty acid dimethylamide) and chlorinated hydrocarbons.
  • 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
  • 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 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. ⁇
  • SC Suspension concentrates
  • SCs 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.
  • 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 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)).
  • 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).
  • DS powder for dry seed treatment
  • SS water soluble powder
  • WS water dispersible powder for slurry treatment
  • CS capsule suspension
  • 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. - 4o -
  • 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 ' opropyl- and tri-wopropyl-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
  • 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);
  • alkylene oxides such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof
  • fatty alcohols such as oleyl alcohol or cetyl alcohol
  • 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
  • alkanolamides alkanolamides
  • simple esters for example fatty acid polyethylene glycol esters
  • amine oxides for example lauryl dimethyl amine oxide
  • lecithins alkanolamides
  • simple esters for example fatty acid polyethylene glycol esters
  • amine oxides for example lauryl dimethyl amine oxide
  • lecithins 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 locus of the pests such as a habitat of the pests, or a growing plant liable to infestation by the pests
  • 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 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).
  • 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).
  • 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.
  • 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.
  • suitable pesticides include the following:
  • 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.
  • 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.
  • suitable pesticides include the following:
  • a) Pyrethroids such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin and gamma cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, S-bioallethrin, fenfluthrin, prallethrin, acrinathirin, etofenprox or
  • 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; 5Q c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencar
  • Benzoyl ureas such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron, diafenthiuron, lufeneron, novaluron, noviflumuron or chlorfluazuron;
  • Organic tin compounds such as cyhexatin, fenbutatin oxide or azocyclotin;
  • Pyrazoles such as tebufenpyrad, tolfenpyrad, ethiprole, pyriprole, fipronil, and fenpyroximate;
  • Macrolides such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad, azadirachtin, milbemectin, lepimectin or spinetoram;
  • Organochlorine compounds such as endosulfan (in particular alpha-endosulfan), benzene hexachloride,
  • Amidines such as chlordimeform or amitraz
  • Fumigant agents such as chloropicrin, dichloropropane, methyl bromide or metam
  • Neonicotinoid compounds such as imidacloprid, thiacloprid, acetamiprid, nitenpyram, dinotefuran, thiamethoxam, clothianidin, or nithiazine;
  • Diacylhydrazines such as tebufenozide, chromafenozide or methoxyfenozide
  • Diphenyl ethers such as diofenolan or pyriproxifen
  • Ketoenols such as Spirotetramat, spirodiclofen or spiromesifen
  • Diamides such as flubendiamide, chlorantraniliprole (Rynaxypyr®) or cyantraniliprole;
  • Essential oils such as Bugoil® - (Plantlmpact); or
  • a comopund selected from buprofezine, flonicamid, acequinocyl, bifenazate, cyenopyrafen, cyflumetofen, etoxazole, flometoquin, fluacrypyrim, fluensulfone, flufenerim, flupyradifuone, harpin, iodomethane, dodecadienol, pyridaben, pyridalyl, pyrimidifen, flupyradifurone, 4-[(6-Chloro-pyridin-3- ylmethyl)-(2,2-difluoro-ethyl)-amino]-5H-furan-2-one (DE 102006015467), CAS: 915972-17-7
  • pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition.
  • 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.
  • 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).
  • acaricidal ovo-larvicides such as clofentezine, flubenzimine, hexythiazox or tetradifon
  • acaricidal motilicides such as dicofol or propargite
  • acaricides such as bromopropylate or chlorobenzilate
  • growth regulators such
  • fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide (SSF-129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-l -sulfonamide,
  • acibenzolar-S-methyl alanycarb, aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, biloxazol, bitertanol, bixafen, blasticidin S, boscalid, bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulfate, copper tallate and Bordeaux mixture, cyclufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulfide
  • OjO-di-wo-propyl-S-benzyl thiophosphate dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol, ethyl-(Z)-N-benzyl-N-([methyl(methyl-thioethylideneamino- oxycarbonyl)amino]thio)- -alaninate, etridiazole, famoxadone, fenamidone (RPA407213), fenarimol, fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin, fenpropimorph,
  • fluoxastrobin fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, fluxapyroxad, folpet, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbamate, isoprothiolane, isopyrazam, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY248908, mancozeb, mandipropamid, maneb, mefenoxam, metalaxyl, mepanipyrim, me
  • biological agents may be included in the composition of the invention e.g. Baciullus species such as Bacillus firmus, Bacillus cereus, Bacillus subtilis, and Pasteuria species such as Pasteuria penetrans and Pasteuria nishizawae.
  • Bacillus firmus strain is strain CNCM 1-1582 which is commercially available as BioNemTM.
  • a suitable Bacillus cereus strain is strain CNCM 1-1562. Of both Bacillus strains more details can be found in US 6,406,690.
  • Other biological organisms that may be included in the compositions of the invention are bacteria such as Streptomyces spp. such as S.
  • avermitilis and fungi such as Pochonia spp. such as P. chlamydosporia.
  • Pochonia spp. such as P. chlamydosporia.
  • Metarhizium spp. such as M. anisopliae
  • Pochonia spp. such as P. chlamydosporia.
  • 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.
  • 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 PIXTM.
  • 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.
  • other formulation types may be prepared.
  • one active ingredient is a water insoluble solid and the other a water insoluble liquid
  • the resultant composition is a suspoemulsion (SE) formulation.
  • 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.
  • 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.
  • the invention provides a compound of the invention for use in a method of therapeutic treatment.
  • 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.
  • the invention relates to a compound of the invention for controlling parasitic invertebrate pests in or on an animal.
  • 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
  • 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.
  • 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.
  • the invention relates to a compound of the invention for use in protecting an animal from a parasitic invertebrate pest.
  • 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.
  • 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.
  • the invention relates to a compound of the invention for use in treating an animal suffering from a parasitic invertebrate pest.
  • 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.
  • the invention provides a pharmaceutical composition
  • 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.
  • 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.
  • 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,
  • 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.
  • 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.
  • 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, me
  • 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.
  • Arthropod growth regulators a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron,
  • eflubenzuron triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole, chlorfentazine
  • ecdysone antagonists halofenozide, methoxyfenozide, tebufenozide
  • juvenoids pyriproxyfen, methoprene (including S-methoprene), fenoxycarb
  • lipid biosynthesis inhibitors spirodiclofen.
  • 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, hydr
  • 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
  • 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.
  • the compounds of the invention are preferably used in combination with the following: 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, tric
  • ratios of a compound of formula I combined with any additional active ingredient 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
  • 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.
  • salts of chemical compounds are in equilibrium with their corresponding non salt forms, salts share the biological utility of the non salt forms.
  • salts of compounds 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
  • 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.
  • 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).
  • 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.
  • 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 WO 03/024222.
  • 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.
  • a spray composition comprises a pesticidally effective amount of a compound of the invention and a propellant.
  • 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.
  • 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), cultured fish, honeybees.
  • fatalities and performance reduction in terms of meat, milk, wool, skins, eggs, etc.
  • controlling parasites may help to prevent the transmittance of infectious agents, the term "controlling" referring to the veterinary field, meaning that the active compounds are effective in reducing the incidence of the respective parasite in an animal infected with such parasites to innocuous levels, e.g. the active compound is effective in killing the respective parasite, inhibiting its growth, or inhibiting its proliferation.
  • 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.
  • 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
  • the animal is preferably a vertebrate, and more preferably a mammal, avian or fish.
  • 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 e.g., 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.
  • 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.
  • inventions 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.
  • marsupials such as kangaroos
  • reptiles such as farmed turtles
  • 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. and protozoae, such as coccidia).
  • helminthiasis The disease or group of diseases described generally as helminthiasis is due to infection of an animal host with parasitic worms known as helminths.
  • 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.
  • 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 , Ancylostoma,
  • 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, Strongy ides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichonema, Trichostrongylus, Trichuris, Uncinaria and Wuchereria.
  • Oesophagostomum Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris.
  • 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.
  • 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.
  • 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, (6 th Edition 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 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).
  • insects such as flies (stinging and licking), parasitic fly larvae, lice, hair lice, bird lice, fleas and the like
  • acarids such as ticks, for examples hard ticks or soft ticks, or mites, such as scab mites, harvest mites, bird mites and the like.
  • 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,
  • 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,
  • 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.
  • 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).
  • Ctenocephalides spp. such as dog flea ⁇ Ctenocephalides canis
  • cat flea Ctenocephalides felis
  • Xenopsylla spp. such as oriental rat flea (Xenopsylla cheopis)
  • 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.
  • 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.
  • 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.
  • flies such as Haematobia (Lyperosia) irritans (horn fly), Simulium spp.
  • 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
  • mites such as Psoroptes spp., Sarcoptes scabei, Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear mites).
  • species of animal health pesets include those 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.
  • 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.
  • Ornithonyssus spp. Pneumonyssus spp., RailUetia 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 turanic
  • Neotrombicula desaleri Neoschongastia xerothermobia, Trombicula akamushi, Otodectes cynotis, Notoedres cati, Sarcoptis canis, Sarcoptes bovis, Sarcoptes ovis, Sarcoptes rupicaprae (S.
  • Ctenocephalides felis, Lucilia cuprina examples include Ornithodoros spp., Ixodes spp., Boophilus spp..
  • 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; or 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.
  • enteral administration in the form of, for example, tablets, capsules, drinks, drenching preparations, granulates, pastes, boli, feed- through procedures, or suppositories
  • parenteral administration such as, for example, by injection (including intramuscular, subcutaneous
  • compounds of the invention 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.
  • the biologically active ingredients may be administered simultaneously or sequentially.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • active ingredients e.g., a salt of an active compound
  • 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.
  • the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.
  • 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.
  • 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.
  • a suitable propellant e.g., without limitation, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane or carbon dioxide.
  • 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 r c
  • - 65 - compound of the invention one or more carriers selected from binders and fillers suitable for oral administration and feed concentrate carriers).
  • 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).
  • lubricants e.g., magnesium stearate
  • disintegrating agents e.g., cross-linked
  • 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.
  • adhesives e.g., acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate
  • a composition of the present invention is formulated into a chewable and/or edible product (e.g., a chewable treat or edible tablet).
  • 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.
  • 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.
  • 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 , ,
  • Liposomes and emulsions are well-known examples of delivery vehicles or carriers for hydrophobic drugs.
  • 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.
  • 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.
  • 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.
  • 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).
  • Step A tert-butyl N-[5-[(3S)-3-benzylsulfanyl-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)butanoyl]indan-l- yl]carbamate
  • the reaction mixture was stirred at -40°C for 17 hours, then more catalyst was added (232 mg). After 4 hours, more catalyst was added (232 mg) and the temperature was increased to -30°C. After another 2 hours, more catalyst was added (116 mg). The reaction mixture was stirred at -30°C for 18 hours, then more catalyst was added (116 mg) and more phenymethanethiol (1.66 ml) was added to the solution. The reaction mixture was then stirred at -20°C for 4 days. Then the temperature was raised to room temperature and after 2 hours, the reaction mixture was quenched with addition of brine then the mixture was extracted with ethyl acetate. The organic layers were combined and dried over sodium sulphate, then concentrated under reduced pressure to give a yellow oil.
  • StepB tert-butyl N-[5-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l - yl]carbamate (B4)
  • the enriched N-[5-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l- yl]cyclopropanecarboxamide could be prepared starting from : tert-butyl N-[5-[(5S)-5-(3,4,5- trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l-yl]carbamate.
  • Type of column Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60°C.
  • Cotton leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with 5 LI larvae. The samples were checked for mortality, feeding behavior, and growth regulation 3 days after treatment (DAT).
  • the following compound gave at least 80% control of Spodoptera Uttoralis: Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B18, B19, B20, B21 , B22, B23, B24, B25, B26, B27 B29, B30, B31, B32, B33, B34, B35, B36, B37, B38, B39, B40, B41 , B42, B43, B44, B45, B46, B47, B49, B50, B52, B53.
  • Eggs (0-24 h old) were placed in 24-well microtiter plate on artificial diet and treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After an incubation period of 4 days, samples were checked for egg mortality, larval mortality, and growth regulation.
  • MTP microtiter plate
  • the following compound gave at least 80%> control of Plutella xylostella: Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B18, B19, B20, B21 , B22, B23, B24, B25, B26, B27, B28, B30, B31, B32, B33, B34, B35, B36, B37, B38, B39, B40, B41 , B42, B43, B44, B45, B46, B47, B49, B50, B51, B52, B53.
  • Diabrotica balteata (Corn root worm):
  • MTP microtiter plate
  • test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After drying, the MTPs were infested with L2 larvae (6-10 per well). After an incubation period of 5 days, samples were checked for larval mortality and growth regulation.
  • Diabrotica balteata Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B18, B19, B20, B21 , B22, B23, B24, B25, B26, B27, B28, B29, B30, B31 , B32, B33, B34, B35, B36, B37, B38, B39, B40, B41, B42, B43, B44, B45, B46, B47, B49, B50, B51 , B52, B53.
  • Thrips tabaci Onion thrips
  • Sunflower leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with a thrips population of mixed ages. After an incubation period of 7 days, samples were checked for mortality.
  • Thrips tabaci Bl, B2, B3, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B19, B20, B21 , B22, B23, B24, B25, B27, B29, B30, B31 , B32, B33, B34, B35, B36, B37, B38, B39, B40, B41, B42, B43, B44, B45, B46, B47, B49, B50, B52, B53.
  • Tetranychus urticae (Two-spotted spider mite):
  • Bean leaf discs on agar in 24-well microtiter plates were sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs are infested with mite populations of mixed ages. 8 days later, discs are checked for egg mortality, larval mortality, and adult mortality.
  • the following compound gave at least 80%> control of Tetranychus urticae: Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B19, B20, B21, B22, B23, B24, B25, B26, B27, B28, B30, B31 , B32, B33, B34, B35, B36, B37, B38, B39, B40, B41, B42, B43, B44, B45, B46, B47, B49, B50, B51 , B52, B53.
  • Cotton plants in the 5 th leaf stage are treated in an automated turn table spray chamber with compounds of the invention at a desired rate of application. Plants are stored in the greenhouse length during the whole test period. 2,16 and optionally 10 days after treatment 4 leaves from each sample are excised, placed into 14cm plastic petri dishes on wet filter paper. The infestation of 10 L3-Spodoptera littoralis is made immediately afterwards. After an incubation period of 6 days the samples are checked for mortality. It has been found that compounds containing an isothiazoline ring are highly potent 2 days after application but lose significant activity 16 days after application. On the other hand, compounds containing an isoxazoline ring lose little activity 16 days after application. This suggests that compounds flick ,

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Abstract

The present invention provides compounds of formula (I) and their use in methods of controlling insects, acarines, nematodes or molluscs.

Description

ISOTHIAZOLE DERIVATIVES AS INSECTICIDAL COMPOUNDS
The present invention relates to certain isothiazoline derivatives, to processes and intermediates for preparing these derivatives, to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising these derivatives and to methods of using these derivatives to control insect, acarine, nematode and mollusc pests.
Certain isoxazoline derivatives with insecticidal properties are disclosed, for example, in EP 1,731,512. However there is a continuing need to find new biologically active compounds as well as new biologically active compounds displaying superior properties for use as agrochemical active ingredients, for example greater biological activity, different spectrum of activity, increased safety profile, or increased biodegradability.
It has now surprisingly been found that certain isothiazoline derivatives have insecticidal properties and increased biodegradability.
The present invention therefore provides compounds of formula (I)
Figure imgf000002_0001
wherein
A1, A2, and A3 are independently of each other C-H, C-R7, or nitrogen;
X1 represents a two- to four-membered bridge containing carbon atoms as bridge members, optionally containing one or more double bonds, and each bridge member is optionally substituted by one or two R6;
R1 is Ci-Cghaloalkyl;
R2 is aryl or aryl substituted by one to five R11, or heteroaryl or heteroaryl substituted by one to five R11;
R3 is hydrogen,
Figure imgf000002_0002
or CrCi2alkyl substituted by one to five R8, C3-C8cycloalkyl or C3- Cgcycloalkyl substituted by one to five R9, C2-Ci2alkenyl or C2-Ci2alkenyl substituted by one to five R8, C2-Ci2alkynyl or C2-Ci2alkynyl substituted by one to five R8, cyano, Ci_Ci2alkoxycarbonyl or Ci_
Ci2alkoxycarbonyl substituted by one to five R8, Ci-Ci2alkoxythiocarbonyl or Ci-Ci2alkoxythiocarbonyl substituted by one to five R8;
R4 is hydrogen, NH2, hydroxyl, C1-C12 alkoxy or Ci-Ci2alkoxy substituted by one to five R8, d- Ci2alkylcarbonylamino or Ci-Ci2alkylcarbonylamino wherein the alkyl is substituted by one to five R8, Ci-Ci2alkylamino or Ci-Ci2alkylamino wherein the alkyl is substituted by one to five R8, Ci-Ci2alkyl or Ci-Ci2alkyl substituted by one to five R8, C3-C8cycloalkyl or C3-C8cycloalkyl substituted by one to five R9, cyano, C2-Ci2alkenyl or C2-Ci2alkenyl substituted by one to five R8, C2-Ci2alkynyl or C2-Ci2alkynyl substituted by one to five R8,
Figure imgf000003_0001
substituted by one to five R8, Ci-Ci2alkoxycarbonyl or d-C^alkoxycarbonyl substituted by one to five R8 or is selected from CH2-R13, C(=0)R13 and C(=S)R13;
R5 is hydrogen, cyano, carbonyl, thiocarbonyl, d-C^alkylcarbonyl or C1-C12 alkylcarbonyl substituted by one to five R8,
Figure imgf000003_0002
or Ci-Cnalkylthiocarbonyl substituted by one to five R8, Ci-Ci2alkylaminocarbonyl or Ci-Cnalkylaminocarbonyl wherein the alkyl is substituted by one to five R8, Ci-Ci2alkylaminothiocarbonyl or
Figure imgf000003_0003
wherein the alkyl is substituted by one to five R8, C2-C24 (total carbon number) dialkylaminocarbonyl or C2-C24 (total carbon number) dialkylaminocarbonyl wherein one or both alkyl is substituted by one to five R8, C2-C24 (total carbon number) dialkylaminothiocarbonyl or C2-C24 (total carbon number) dialkylaminothiocarbonyl wherein one or both alkyl is substituted by one to five R8,
Figure imgf000003_0004
or Q- Ci2alkoxyaminocarbonyl wherein the alkoxy is substituted by one to five R8, Q- Ci2alkoxyaminothiocarbonyl or
Figure imgf000003_0005
wherein the alkoxy is substituted by one to five R8, Ci-Ci2alkoxycarbonyl or
Figure imgf000003_0006
substituted by one to five R8, Q- Ci2alkoxythiocarbonyl or substituted by one to five R8, Q- Ci2thioalkoxycarbonyl or
Figure imgf000003_0007
substituted by one to five R8, Q- Ci2thioalkoxythiocarbonyl or Ci-Ci2thioalkoxythiocarbonyl substituted by one to five R8, Q- Ci2alkylsulfonyl or
Figure imgf000003_0008
substituted by one to five R8, C3-Ci2cycloalkylcarbonyl or C3- Ci2cycloalkylcarbonyl substituted by one to five R9, C2-Ci2alkenylcarbonyl or C2-Ci2alkenylcarbonyl substituted by one to five R8, C2-Ci2alkynylcarbonyl or C2-Ci2alkynylcarbonyl substituted by one to five R8, C3-Ci2cycloalkyl-Ci-Ci2alkylcarbonyl or C3-Ci2cycloalkyl-Ci-Ci2alkylcarbonyl substituted by one to five R9, Ci-Ci2alkylsulfenyl-Ci-Ci2alkylcarbonyl or Ci-C^alkylsulfenyl-Q-C^alkylcarbonyl substituted by one to five R8, Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl or Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl substituted by one to five R8, C1-C12
Figure imgf000003_0009
Ci2alkylcarbonyl substituted by one to five R8, Q-C^alkylcarbonyl-Ci-C^alkylcarbonyl or Cr
Ci2alkylcarbonyl-Ci-Ci2alkylcarbonyl substituted by one to five R8, C3-Ci2cycloalkylaminocarbonyl or C3-Ci2cycloalkylaminocarbonyl wherein the cycloalkyl is substituted by one to five R9, C2- Ci2alkenylaminocarbonyl or C2-Ci2alkenylaminocarbonyl wherein the alkenyl is substituted by one to five R8, C2-Ci2alkynylaminocarbonyl or C2-Ci2alkynylaminocarbonyl wherein the alkynyl is substituted by one to five R8, or is selected from C(=0)R13 and C(=S)R13;
or R4 and R5 together with the nitrogen atom to which they are bound, form a 3- to 6-membered heterocyclic ring which may be substituted by one to five R14, or may be substituted with a keto, thioketo or nitroimino group;
each R6 is independently hydrogen, halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, C2- Cgalkenyl, C2-C8haloalkenyl, C2-Cgalkynyl, C2-Cghaloalkynyl, hydroxy, CpCgalkoxy, CpCghaloalkoxy, mercapto, Ci-C8alkylthio, Ci-Cghaloalkylthio, CpCgalkylsulfinyl, CpCghaloalkylsulfinyl, Cr Cgalkylsulfonyl, CpCghaloalkylsulfonyl, CpCgalkylcarbonyl, Ci-Cgalkoxycarbonyl, aryl or aryl substituted by one to five R12, or heterocyclyl or heterocyclyl substituted by one to five R12;
each R7 is independently halogen, cyano, nitro, CpCgalkyl, C3-Cgcycloalkyl, Ci-Cghaloalkyl, C2- Cgalkenyl, C2-Cghaloalkenyl, C2-Cgalkynyl, C2-Cghaloalkynyl, Ci-Cgalkoxy, Ci-Cghaloalkoxy, Cp Cgalkoxycarbonyl-, or two R7 on adjacent carbon atoms together form a -CH=CH-CH=CH- bridge or a - N=CH-CH=CH- bridge;
each R8 is independently halogen, cyano, nitro, hydroxy, NH2, mercapto, CpCgalkyl, Q- Cghaloalkyl, C3-Cgcycloalkyl, Q-Cgalkoxy, Ci-Cghaloalkoxy, Ci-Cgalkylthio, Ci-Cghaloalkylthio, Cp Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, Ci-Cgalkylsulfonyl, Ci-Cghaloalkylsulfonyl, Ci-Cgalkylamino, C2-Cgdialkylamino, C3-Cgcycloalkylamino, CpCgalkylcarbonyl, Ci-Cgalkoxycarbonyl, d-
Cgalkylaminocarbonyl, Ci-Cgdialkylaminocarbonyl, Ci-Cghaloalkylcarbonyl, Ci-Cghaloalkoxycarbonyl, Ci -Cghaloalkylaminocarbonyl, C 1 -Cghalodialkylaminocarbonyl;
each R9 is independently halogen, cyano or Q-Cgalkyl;
each R10 is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, C2-C8alkenyl, C2- Cghaloalkenyl, C2-C8alkynyl, C2-C8haloalkynyl, hydroxy, Q-Cgalkoxy, Ci-Cghaloalkoxy, mercapto, Ci- Cgalkylthio, CpCghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, CpCgalkylsulfonyl, Cr Cghaloalkylsulfonyl, CpCgalkylcarbonyl, Ci -Cgalkoxycarbonyl, aryl or aryl substituted by one to five R12, or heterocyclyl or heterocyclyl substituted by one to five R12;
each R11 is independently hydrogen, halogen, cyano, nitro, Q-Cgalkyl, Ci-Cghaloalkyl, C2- Cgalkenyl, C2-Cghaloalkenyl, C2-Cgalkynyl, C2-Cghaloalkynyl, hydroxy, Ci-Cgalkoxy, Ci-Cghaloalkoxy, mercapto, Ci-Cgalkylthio, Ci-Cghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, Cr
Cgalkylsulfonyl, CpCghaloalkylsulfonyl, CpCgalkylcarbonyl, Ci-Cgalkoxycarbonyl, aryl or aryl substituted by one to five R12, or heterocyclyl or heterocyclyl substituted by one to five R12;
each R12 is independently halogen, cyano, nitro, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy-, or Cr C4haloalkoxy-;
R13 is aryl or aryl substituted by one to five R10, heterocyclyl or heterocyclyl substituted by one to five R10;
each R14 is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, Q-Cgalkoxy, Cr Cghaloalkoxy or Ci-Cgalkoxycarbonyl;
or a salt or N-oxide thereof.
The compounds of formula (I) may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. The invention also covers salts and N-oxides.
The compounds of the invention may contain one or more asymmetric carbon atoms, for example, at the -CR'R2- group, and may exist as enantiomers (or as pairs of diastereoisomers) or as mixtures of such.
Alkyl groups (either alone or as part of a larger group, such as alkoxy-, alkylthio-, alkylsulfinyl-, alkylsulfonyl-, alkylcarbonyl- or alkoxycarbonyl-) can be in the form of a straight or branched chain and are, for example, methyl, ethyl, propyl, prop-2-yl, butyl, but-2-yl, 2 -methyl-prop -1 -yl or 2-methyl-prop-2- yl. The alkyl groups are preferably Ci-Ce, more preferably C -C4, most preferably C1-C3 alkyl groups. Where an alkyl moiety is said to be substituted, the alkyl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
Alkylene groups can be in the form of a straight or branched chain and are, for example, -CH2-
, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-CH2-, -CH(CH3)-CH2-, or -CH(CH2CH3)-. The alkylene groups are preferably C1-C3, more preferably C1-C2, most preferably Ci alkylene groups.
Alkenyl groups can be in the form of straight or branched chains, and can be, where appropriate, of either the (E)- or (Z)-configuration. Examples are vinyl and allyl. The alkenyl groups are preferably C2-C6, more preferably C2-C4, most preferably C2-C3 alkenyl groups.
Alkynyl groups can be in the form of straight or branched chains. Examples are ethynyl and propargyl. The alkynyl groups are preferably C2-C6, more preferably C2-C4, most preferably C2-C3 alkynyl groups.
Halogen is fluorine, chlorine, bromine or iodine.
Haloalkyl groups (either alone or as part of a larger group, such as haloalkoxy-, haloalkylthio-, haloalkylsulfinyl- or haloalkylsulfonyl-) are alkyl groups which are substituted by one or more of the same or different halogen atoms and are, for example, difluoromethyl, trifluoromethyl,
chlorodifluoromethyl or 2,2,2-trifluoro-ethyl.
Haloalkenyl groups are alkenyl groups which are substituted by one or more of the same or different halogen atoms and are, for example, 2,2-difluoro-vinyl or 1 ,2-dichloro-2-fluoro-vinyl.
Haloalkynyl groups are alkynyl groups which are substituted by one or more of the same or different halogen atoms and are, for example, l -chloro-prop-2-ynyl.
Cycloalkyl groups or carbocyclic rings can be in mono- or bi-cyclic form and are, for example, cyclopropyl, cyclobutyl, cyclohexyl and bicyclo[2.2.1 ]heptan-2-yl. The cycloalkyl groups are preferably C3-C8, more preferably C3-C6 cycloalkyl groups. Where a cycloalkyl moiety is said to be substituted, the cycloalkyl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
Aryl groups (either alone or as part of a larger group, such as aryl-alkylene-) are aromatic ring systems which can be in mono-, bi- or tricyclic form. Examples of such rings include phenyl, naphthyl, anthracenyl, indenyl or phenanthrenyl. Preferred aryl groups are phenyl and naphthyl, phenyl being most preferred. Where an aryl moiety is said to be substituted, the aryl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
Heteroaryl groups (either alone or as part of a larger group, such as heteroaryl-alkylene-) are aromatic ring systems containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings will contain up to three heteroatoms and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulfur. Examples of monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (e.g. 1.2.4 triazoyl), furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl and thiadiazolyl. Examples of bicyclic groups include purinyl, quinolinyl, cinnolinyl, quinoxalinyl, indolyl, indazolyl, benzimidazolyl, benzothiophenyl and benzothiazolyl. Monocyclic heteroaryl groups are preferred, pyridyl being most preferred. Where a heteroaryl moiety is said to be substituted, the heteroaryl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
Heterocyclyl groups or heterocyclic rings (either alone or as part of a larger group, such as heterocyclyl-alkylene-) are defined to include heteroaryl groups and in addition their unsaturated or partially unsaturated analogues. Examples of monocyclic groups include isoxazolyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, [l,3]dioxolanyl, piperidinyl, piperazinyl, [l,4]dioxanyl, and morpholinyl or their oxidised versions such as 1 -oxo-thietanyl and 1,1-dioxo-thietanyl. Examples of bicyclic groups include 2,3-dihydro-benzofuranyl, benzo[l,4]dioxolanyl, benzo[l,3]dioxolanyl, chromenyl, and 2,3- dihydro-benzo[l,4]dioxinyl. Where a heterocyclyl moiety is said to be substituted, the heterocyclyl moiety is preferably substituted by one to four substituents, most preferably by one to three substituents.
Preferred values of A1, A2, A3, R1, R2, R3, R4, R5, R6, R7, R8, R9 , R10, R11, R12, R13, R14 and R15 are, in any combination, as set out below.
Preferably no more than two of A1, A2, and A3 are nitrogen, more preferably no more than two of
A 1 , A2 and A 3 are nitrogen and A 2 and A 3 are not both nitrogen. Even more preferably A 1 , A2 and A3 are independently C-H or nitrogen, wherein no more than two of A1, A2 and A3 are nitrogen, and A2 and A3 are not both nitrogen. Yet even more preferably, A1 is C-H, and A2 and A3 are both C-H or one of A2 and A3 is C-H and the other is nitrogen.
In one group of compounds A1 is C-H or C-R7, most preferably A1 is C-H.
In one group of compounds A2 is C-H or C-R7, most preferably A2 is C-H.
In one group of compounds A3 is C-H or C-R7, most preferably A3 is C-H.
In one group of compounds A1, A2 and A3 are each C-H.
Preferably X1 represents -C(R6)(R6)-C(R6)(R6)-, -C(R6)=C(R6)-,
-C(R6)(R6)-C(R6)(R6)-C(R16)(R6)-, -C(R6)=C(R6)-C(R6)(R6)- or -C(R6)(R6)-C(R6)=C(R6)-; more preferably -C(R6)(R6)-C(R6)(R6)- or -C(R6)(R6)-C(R6)(R6)-C(R6)(R6)-, most
preferably -C(R6)(R6)-C(R6)(R6)- . When R6 is hydrogen (preferred) these ring fragments
are -CH2-CH2-, -CH=CH-, -CH2-CH2-CH2-, -CH=CH-CH2- or -CH2-CH=CH-.
Preferably R1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl, more preferably chlorodifluoromethyl or trifluoromethyl, most preferably trifluoromethyl.
Preferably R2 is aryl or aryl substituted by one to three R11, more preferably R2 is phenyl or phenyl substituted by one to three R11, pyridyl or pyridyl substituted by one to three R11, more preferably R2 is phenyl substituted by one to three R11 or pyridyl substitued by one to three R11, more preferably R2 is group P
Figure imgf000007_0001
2 11 2 11 11
wherein X is N or C-R , preferably X is C-R . Preferably at least two R are not hydrogen.
More preferably R2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4-chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro-5-fluorophenyl-, 3- chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3 ,5 -bis(trifluoromethyl)phenyl-, 3 -(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, more preferably 3,5-dichlorophenyl-, more preferably 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4- pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, most preferably R2 is 3,5-dichlorophenyl.
Preferably, R3 is hydrogen,
Figure imgf000007_0002
d-Cgcycloalkyl, d-Cghalocycloalkyl, C2-Ci2alkenyl or C2-Ci2haloalkenyl, C2-Ci2alkynyl, C2-Ci2haloalkynyl cyano,
Figure imgf000007_0003
Ci_ Ci2haloalkoxycarbonyl,
Figure imgf000007_0004
Preferably, R3 is hydrogen, halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, , more preferably R3 is hydrogen, halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl or C3-C6 cycloalkyl. More preferably at least R3 is hydrogen, halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl or C3-C6 cycloalkyl, most preferably, hydrogen, methyl, ethyl or cyclopropyl.
Preferably, R4 is hydrogen, NH2, hydroxyl,
Figure imgf000007_0005
d- Ci2alkylcarbonylamino,
Figure imgf000007_0006
Cp d-Cgcycloalkyl, d-Cgh
C
Figure imgf000007_0007
i2haloalkenyl, C2-Ci2alkynyl, C2-Ci2haloalkynyl, d- Cgalkoxycarbonyl, or d-dhaloalkoxycarbonyl. More preferably, R4 is hydrogen, d-Cgalkyl, d- Cghaloalkyl, d-Cgalkoxy, CpCghaloalkoxy, Ci-Cgalkylcarbonyl, d-Cghaloalkylcarbonyl, d- Cgalkoxycarbonyl, or Ci-Cghaloalkoxycarbonyl. Even more preferably R4 is hydrogen, Ci-C4alkyl or d- dhaloalkyl, most preferably hydrogen.
Preferably R5 is hydrogen, cyano, carbonyl, thiocarbonyl, d-d2alkylcarbonyl, d- d2haloalkylcarbonyl, C 1 -C 12alkylthiocarbonyl, d -C i2haloalkylthiocarbonyl, C 1 -C^alkylaminocarbonyl, Ci-Ci2alkylaminothiocarbonyl,
Figure imgf000007_0008
C2- C24 (total carbon number) dialkylaminocarbonyl, C2-C24 (total carbon number) dialkylaminothiocarbonyl, d-d2alkoxyaminocarbonyl, Ci-Ci2alkoxyaminothiocarbonyl, Ci-Ci2alkoxycarbonyl, Ci- Cghaloalkoxycarbonyl, Ci-Ci2alkoxythiocarbonyl,
Figure imgf000007_0009
Cp Ci2thioalkoxycarbonyl,
Figure imgf000008_0001
C3- Ci2cycloalkylcarbonyl, C3-Ci2halocycloalkylcarbonyl, C2-Ci2alkenylcarbonyl, C2- Ci2haloalkenylcarbonyl, C2-C12 alkynylcarbonyl, C2-Ci2haloalkynylcarbonyl, C3-Ci2cycloalkyl-Cr C^alkylcarbonyl, C3-Ci2halocycloalkyl-Ci-Ci2alkylcarbonyl, C2-Ci2alkylsulfenyl-Ci-Ci2alkylcarbonyl, Ci-Ci2haloalkylsulfenyl-Ci-Ci2alkylcarbonyl, Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl, d- Ci2haloalkylsulfinyl-C 1 -C ^alkylcarbonyl, C i-Ci2alkylsulfonyl-C 1 -C ^alkylcarbonyl, C 1 - Ci2haloalkylsulfonyl-Ci-Ci2alkylcarbonyl, Ci-C^alkylcarbonyl-Ci-Cnalkylcarbonyl, Q- Ci2haloalkylcarbonyl-Ci-Ci2alkylcarbonyl, C3-Ci2cycloalkylaminocarbonyl, C2- Ci2alkenylaminocarbonyl, C2-Ci2alkynylaminocarbonyl or C(=0)R13.
More preferably R5 is
Figure imgf000008_0002
Ci-Cnhaloalkylcarbonyl,
Ci-Ci2haloalkylthiocarbonyl, Ci-Ci2alkylaminocarbonyl, Ci-Ci2alkylaminothiocarbonyl, C2-C24 (total carbon number) dialkylaminocarbonyl, C2-C24 (total carbon number) dialkylaminothiocarbonyl, Q- Ci2alkoxyaminocarbon
Ci2haloalkoxycarbonyl,
Ci2thioalkoxycarbonyl,
Figure imgf000008_0003
C3- Ci2cycloalkylcarbonyl, C3-Ci2halocycloalkylcarbonyl, C2-Ci2alkenylcarbonyl, C2- Ci2haloalkenylcarbonyl, C2-Ci2 alkynylcarbonyl, C2-Ci2haloalkynylcarbonyl, C3-Ci2cycloalkyl-Ci- Ci2alkylcarbonyl, C3-Ci2halocycloalkyl-Ci-Ci2alkylcarbonyl, C2-Ci2alkylsulfenyl-Ci-Ci2alkylcarbonyl, Ci-Ci2haloalkylsulfenyl-Ci-Ci2alkylcarbonyl, Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl, Cr
Ci2haloalkylsulfinyl-C 1 -C ^alkylcarbonyl, C i-Ci2alkylsulfonyl-C 1 -C ^alkylcarbonyl, C 1 - Ci2haloalkylsulfonyl-Ci-Ci2alkylcarbonyl, CpC^alkylcarbonyl-Ci-Cnalkylcarbonyl, Q- Ci2haloalkylcarbonyl-Ci-Ci2alkylcarbonyl, C3-Ci2cycloalkylaminocarbonyl, C2-
Ci2alkenylaminocarbonyl, C2-Ci2alkynylaminocarbonyl or or C(=0)R13 wherein R13 is phenyl or phenyl substituted by one to five R14, or pyridyl or pyridyl substituted by one to four R14.
More preferably R5 is
Figure imgf000008_0004
CpCnhaloalkylcarbonyl, C3- Ci2cycloalkylcarbonyl, C3-Ci2halocycloalkylcarbonyl, C3-Ci2cycloalkyl-Ci-Ci2alkylcarbonyl, C3- Ci2halocycloalkyl-Ci-Ci2alkylcarbonyl, CpC^alkylsulfenyl-Ci-C^alkylcarbonyl, Cr
Ci2haloalkylsulfenyl-Ci-Ci2alkylcarbonyl, Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl, Cr
Ci2haloalkylsulfinyl-C 1 -C
Figure imgf000008_0005
C 1 - Ci2haloalkylsulfonyl-Ci-Ci2alkylcarbonyl,
Figure imgf000008_0006
C3-Ci2cycloalkylaminocarbonyl, or C(=0)R13 wherein R13 is phenyl or phenyl substituted by one to five R14, or pyridyl or pyridyl substituted by one to four R14.
More preferably R5 is Ci-Cgalkylcarbonyl, Ci-Cghaloalkylcarbonyl, d-C^alkoxycarbonyl, C3- Cgcycloalkylcarbonyl, C3-Cghalocycloalkylcarbonyl, C3-Cgcycloalkyl-CH2-carbonyl, C3- Cghalocycloalkyl-CH2-carbonyl, Ci-Cgalkylsulfenyl-CH2-carbonyl, Ci-Cghaloalkylsulfenyl-CH2-carbonyl, Ci-Cgalkylsulfinyl-CH2-alkylcarbonyl, Ci-Cghaloalkylsulfinyl-CH2-carbonyl, Ci-Cgalkylsulfonyl-CH2- alkylcarbonyl, or Ci-Cghaloalkylsulfonyl-CH2— carbonyl, Ci-Cgalkylaminocarbonyl, C3- - o -
Cgcycloalkylaminocarbonyl, or C(=0)R13, wherein R13 is phenyl or phenyl substituted by one to five R14, or pyridyl or pyridyl substituted by one to four R14.
In one group of compounds R5 is hydrogen, cyano, carbonyl, thiocarbonyl, d-C^alkylcarbonyl,
Figure imgf000009_0001
Ci2alkylaminocarbonyl,
Figure imgf000009_0002
d- Ci2haloalkylaminothiocarbonyl, C2-C24 (total carbon number) dialkylaminocarbonyl, C2-C24 (total carbon number) dialkylaminothiocarbonyl,
Figure imgf000009_0003
d- Ci2alkoxycarbonyl,
Figure imgf000009_0004
Ci-Ci2thioalkoxycarbonyl, Ci-Ci2thioalkoxythiocarbonyl,
Figure imgf000009_0005
C3-Ci2cycloalkylcarbonyl, C3-Ci2halocycloalkylcarbonyl, C2-Ci2alkenylcarbonyl, d- Ci2haloalkenylcarbonyl, C2-Ci2 alkynylcarbonyl, C2-Ci2haloalkynylcarbonyl, C3-Ci2cycloalkyl-CH2- carbonyl, C3-Ci2halocycloalkyl-CH2-carbonyl, C2-Ci2alkylsulfenyl-CH2-carbonyl, Cr
Ci2haloalkylsulfenyl-CH2-carbonyl, Ci-Ci2alkylsulfinyl-CH2-carbonyl, Ci-Ci2haloalkylsulfinyl-CH2- carbonyl, Ci-Ci2alkylsulfonyl-CH2-carbonyl, Ci-Ci2haloalkylsulfonyl-CH2-carbonyl, Q- Ci2alkylcarbonyl-CH2-carbonyl, Ci-Ci2haloalkylcarbonyl-CH2-carbonyl, C3-Ci2cycloalkylaminocarbonyl, C2-Ci2alkenylaminocarbonyl, C2-Ci2alkynylaminocarbonyl.
In one group of compounds R4 and R5 together with the nitrogen atom to which they are bound form a ring, preferably it is a 3 - to 6-membered heterocyclic ring which may be substituted by one to five R14, or may be substituted with a keto, thioketo or nitroimino group.
In one group of compounds R5 is C(=0)-R15, wherein R15 is Ci-C4alkyl, Ci-C4haloalkyl, C3- C6cycloalkyl, C3-C6cycloalkyl-Ci-C4alkyl, C3.C6halocycloalkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl, CrC4haloalkoxy-CrC4alkyl, CrC4 alkylthio-CrC4alkyl, d-Qalkylsulfmyl-d-Qalkyl, Cr
dalkylsulfonyl-Ci-C alkyl, Ci-C alkylamino, Ci-C haloalkylamino, d-Cgcycloalkylamino, phenyl optionally substituted by halogen or pyridylmethyl; preferably R15 is methyl, ethyl, cyclopropyl, cyclopropylmethyl, 2,2,2-trifluoroethyl, 2-methoxyethyl, methylthiomethyl, methylsulfinylmethyl, methylsulfonylmethyl, methylamino, ethylamino, 2,2,2-trifluoroethylamino, cyclopropylamino, cyclopropylmethylamino, 2,4,6-trifluorophenyl or pyridylmethyl; most preferably R15 is methyl, ethyl, 2,2,2-trifluoroethyl or cyclopropyl.
Preferably each R7 is independently halogen, cyano, nitro, d-dalkyl, d-dcycloalkyl, d- Cghaloalkyl, d-Cgalkenyl, Ci-Cgalkoxy or d-dhaloalkoxy, or two R7 on adjacent carbon atoms together form a -CH=CH-CH=CH- bridge, more preferably halogen, cyano, nitro, d-dalkyl, - alkenyl, C3- Cgcycloalkyl, Ci-Cghaloalkyl, Ci-Cgalkoxy or d-dhaloalkoxy, even more preferably bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, cyclopropyl, vinyl, methoxy, trifluoromethoxy, yet even more preferably bromo, chloro, fluoro, cyclopropyl, trifluoromethyl, vinyl, or methyl, ethyl, nitro, cyano, most preferably bromo, chloro, fluoro, or methyl.
Preferably, each R8 is independently halogen, cyano, nitro, hydroxy, Ci-Cgalkoxy, d- Cghaloalkoxy, Ci-Cgalkylcarbonyl, d-Cgalkoxycarbonyl, mercapto, Ci-Cgalkylthio, Ci-Cghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, CpCgalkylsulfonyl. More preferably, each R8 is independently halogen, cyano, nitro, hydroxy, Q-Cgalkoxy, Q-Cghaloalkoxy, mercapto, CpCgalkylthio, Q- Cghaloalkylthio, more preferably bromo, chloro, fluoro, methoxy, or methylthio, most preferably chloro, fluoro, or methoxy.
Preferably, each R9 is independently cyano, chloro, fluoro or methyl, most preferably each R9 is methyl.
Preferably each R10 is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, d- Cgalkoxy, Ci-Cghaloalkoxy, more preferably bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy, most preferably bromo, chloro, fluoro, cyano or methyl.
Preferably each R11 is independently hydrogen, halogen, cyano, nitro, Q-Cgalkyl, Ci-Cghaloalkyl,
Q-Cgalkoxy, Ci-Cghaloalkoxy, more preferably hydrogen, iodo, bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy, even more preferably hydorgen, bromo, chloro, fluoro, iodo or trifluoromethyl, most preferably hydrogen, bromo, chloro, fluoro or trifluoromethyl.
Preferably each R12 is independently bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy, more preferably bromo, chloro, fluoro, nitro or methyl, most preferably each R12 is independently chloro, fluoro or methyl.
Preferably R13 is phenyl or phenyl substituted by one to five R14, or pyridyl or pyridyl substituted by one to five R14.
Preferably each R14 is independently bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy, more preferably bromo, chloro, fluoro, nitro or methyl, more preferably each R14 is independently chloro, fluoro or methyl.
In one embodiment the present invention provides compounds of formula (I) (embodiment A) wherein A1 is C-H, or nitrogen, A2 and A3 are independently C-H or nitrogen, wherein no more than two of A1, A2 and A3 are nitrogen, and A2 and A3 are not both nitrogen;
R1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl;
R2 is group P
Figure imgf000010_0001
wherein X2 is N or C-R11;
R3 is hydrogen, methyl, ethyl or cyclopropyl;
R4 is hydrogen, Ci-C4alkyl or Ci-C4haloalkyl;
R5 is C(=0)-R15; each R11 is independently hydrogen, bromo, chloro or trifluoromethyl providing that at least two R11 are not hydrogen;
R15 is CrC4alkyl, CrC4haloalkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-Ci-C4alkyl,
C3.C6halocycloalkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl, Ci-C4haloalkoxy-Ci-C4alkyl, C1-C4 alkylthio-Ci-C4alkyl, Ci-C4alkylsulfinyl-Ci-C4alkyl, Ci-C4alkylsulfonyl-Ci-C4alkyl, Ci-C4alkylamino, d- C4haloalkylamino, Cs-Cgcycloalkylamino, phenyl optionally substituted by halogen or pyridylmethyl.
X1 is as defined for the compound of formula I, but preferably represents
-C(R16)(R16)-C(R16)(R16)- or -C(R16)(R16)-C(R16)(R16)-C(R16)(R16)-, more
preferably -CH2-CH2- or -CH2-CH2-CH2-;
In one embodiment the present invention provides compounds of formula (I) (embodiment B) wherein A2, A3 and A4 are C-H and X1, R1, R2, R3, R4 and R5 are as defined for compounds of formula (I); or a salt or N-oxide thereof. The preferences for X1, R1, R2, R3, R4 and R5are the same as the preferences set out for the corresponding substituents of compounds of the formula (I). In particular, X1 preferably represents -C(R6)(R6)-C(R6)(R6)- or
-C(R6)(R6)-C(R6)(R6)-C(R6)(R6)-, more preferably -CH2-CH2- or -CH2-CH2-CH2-;
In a further embodiment the present invention provides compounds of formula (I) (embodiment
C)
1 2 3 2 3 4 wherein A , A and A are independently C-H or nitrogen, wherein no more than two of A , A and A are nitrogen, and A2 and A3 are not both nitrogen;
R1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl;
R2 is group P
Figure imgf000011_0001
X2 is C or N, and X1, R3, R4, R5, and R1 1 are as defined for compounds of formula I; or a salt or N-oxide thereof. The preferences for A1, A2, A3, X'R1, R2, R3, R4, R5, and R1 1 are the same as the preferences set out for the corresponding substituents of compounds of the formula (I). In particular, X1 preferably represents -C(R6)(R6)-C(R6)(R6)- or -C(R6)(R6)-C(R6)(R6)-C(R6)(R6)-, more
preferably -CH2-CH2- or -CH2-CH2-CH2-.
In a further embodiment the present invention provides compounds of formula (I) (embodiment
1 2 3 1 1 2 5 3 4
D) wherein A , A , A X1, R , R" and RJ are as defined in embodiment A but R and R are hydrogen.
In a further embodiment the present invention provides compounds of formula (la) (embodiment
E)
Figure imgf000012_0001
wherein A1, A2, A3, A4, X1, R1, R2, R3, R4 and preferences thereof are as defined for the compound of formula I and R15 is as defined for compounds of formula I. In particular, X1 preferably represents -C(R6)(R6)-C(R6)(R6)- or -C(R6)(R6)-C(R6)(R6)-C(R6)(R6)-, more
preferably -CH2-CH2- or -CH2-CH2-CH2-;
In a further embodiment the present invention provides compounds of formula (lb) (embodiment
F)
Figure imgf000012_0002
1 2 3 1 1 2 3 4 15
wherein A , A , A , X , R , R , R , R , R and preferences thereof are as defined for the compound of formula I. In particular, R4 is preferably hydrogen, R15 is preferably methyl, ethyl, cyclopropyl, cyclopropylmethyl, 2,2,2-trifluoroethyl, 2-methoxyethyl, methylthiomethyl,
methylsulfinylmethyl, methylsulfonylmethyl, methylamino, ethylamino, 2,2,2-trifluoroethylamino, cyclopropylamino, cyclopropylmethylamino, 2,4,6-trifluorophenyl or pyridylmethyl; X1 preferably represents -C(R6)(R6)-C(R6)(R6)- or -C(R6)(R6)-C(R6)(R6)-C(R6)(R6)-, more
preferably -CH2-CH2- or -CH2-CH2-CH2-;
In a further embodiment the invention provides compounds of formula (Ic) (embodiment G)
Figure imgf000013_0001
wherein A1, A2, A3, R1, R2, R4, R5 and R6 and preferences thereof are as defined for compounds of formula I and n is 0 to 4.
In a further embodiment the invention provides compounds of formula (Id) (embodiment H)
Figure imgf000013_0002
wherein A,A,A,R,R,R,R and R and preferences thereof are as defined for compounds of formula I and n is 0 to 5.
Certain intermediates useful in the preparation of compounds of formula I are novel and form further aspects of the invention.
Accordingly, in a further aspect the invention provides compounds of formula (Int-I)
Figure imgf000014_0001
(Int-1)
1 2 3 1 1 2 3
wherein A , A, A X1, R , R , and RJ are as defined for compounds of fomula I, or a salt of N-oxide
1 2 3 1 1 2 3
thereof. The preferences for A , A , A , X , R , R , and R are as defined for compounds of formula I.
In a further aspect the invention provides compounds of formula (Int-2)
1 2 3 1 1 2 3 4 5
wherein A , A, A X1, R , R", R\ R and RJ are as defined for compounds of fomula I, and R is H, cyano, halogen, CpCgalkyl, Ci-Cgalkylcarbonyl, arylsulfinyl wherein the aryl (preferably phenyl) is optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C4alkyl, d- C4haloalkyl, Ci-C4alkoxy and Ci-C4haloalkoxy, arylsulfonyl wherein the aryl (preferably phenyl) is optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C4alkyl, d- C4haloalkyl, Ci-C4alkoxy and Ci-C4haloalkoxy, benzyl optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy and Cp
C4haloalkoxy, or a salt of N-oxide thereof. The preferences for A1, A2, A3, X1, R1, R2, R3, R4 and R5 are as defined for compounds of formula I. R is preferably hydrogen, methylcarbonyl, benzyl or butyl (preferably tbutyl).
The tables below illustrate specific compounds of the invention. Table G
Figure imgf000015_0001
Figure imgf000016_0001
Figure imgf000017_0001
Figure imgf000017_0002
Table 1
Table 1 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 2
Table 2 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 3
Table 3 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 4
Table 4 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 5
Table 5 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 6
Table 6 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-fluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 7
Table 7 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 8
Table 8 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is CH, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 9
Table 9 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 10
Table 10 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -bromophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 11
Table 11 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 12
Table 12 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 13
Table 13 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 14
Table 14 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 15
Table 15 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 16
Table 16 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 17
Table 17 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 18
Table 18 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is CH, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 19
Table 19 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 20
Table 20 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 21
Table 21 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P. Table 22
Table 22 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 23
Table 23 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 24
Table 24 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 25
Table 25 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 26
Table 26 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 27
Table 27 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 28
Table 28 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 29
Table 29 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 30
Table 30 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 31
Table 31 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 32
Table 32 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 33
Table 33 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P. Table 34
Table 34 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 35
Table 35 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is N, A2 is CH, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 36
Table 36 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is N, A2 is CH, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 37
Table 37 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 38
Table 38 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 39
Table 39 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 40
Table 40 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 41
Table 41 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 42
Table 42 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 43
Table 43 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 44
Table 44 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 45
Table 45 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 46
Table 46 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 47
Table 47 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 48
Table 48 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 49
Table 49 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 50
Table 50 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 51
Table 51 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P. Table 52
Table 52 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 53
Table 53 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 54
Table 54 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is CH, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 55
Table 55 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 56
Table 56 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 57 Table 57 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 58
Table 58 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 59
Table 59 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 60
Table 60 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 61
Table 61 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 62
Table 62 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 63
Table 63 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 64
Table 64 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -bromophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 65
Table 65 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 66
Table 66 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 67
Table 67 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 68
Table 68 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 69
Table 69 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P. Table 70
Table 70 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 71
Table 71 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 72
Table 72 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is CH, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 73
Table 73 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 74
Table 74 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P. Table 75
Table 75 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 76
Table 76 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 77
Table 77 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 78
Table 78 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 79
Table 79 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 80
Table 80 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 81
Table 81 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 82
Table 82 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 83
Table 83 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -fluorophenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 84
Table 84 provides 114 compounds of Formula I-A wherein R2 is 3 -chloro-5 -(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 85
Table 85 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 86
Table 86 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 87
Table 87 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P. Table 88
Table 88 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 89
Table 89 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is N, A2 is N, A3 is CH, and Rl , Ga and Gb are as defined in Table P.
Table 90
Table 90 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is N, A2 is N, A3 is CH, and Rl, Ga and Gb are as defined in Table P.
Table 91
Table 91 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 92
Table 92 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 93
Table 93 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 94
Table 94 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 95
Table 95 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 96
Table 96 provides 114 compounds of Formula I-A wherein R2 is 3, 5 -dichloro -4 -fluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 97
Table 97 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, A2 is CH, A2 is N, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 98
Table 98 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 99
Table 99 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 100
Table 100 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 101
Table 101 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-fluorophenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 102
Table 102 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 103
Table 103 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 104
Table 104 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 105
Table 105 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 106
Table 106 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 107
Table 107 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 108
Table 108 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, A2 is CH, A2 is N, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 109
Table 109 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichlorophenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 110 Table 110 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-fluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 111
Table 111 provides 114 compounds of Formula I-A wherein R2 is 3-fluoro-4-chlorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 112
Table 112 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichlorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 113
Table 113 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-4-bromophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 114
Table 114 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-fluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 115
Table 115 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trichlorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 116
Table 116 provides 114 compounds of Formula I-A wherein R2 is 3,5-dichloro-4-iodophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 117
Table 117 provides 114 compounds of Formula I-A wherein R2 is 3,4,5-trifluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 118
Table 118 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-bromophenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 119
Table 119 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-fluorophenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 120
Table 120 provides 114 compounds of Formula I-A wherein R2 is 3-chloro-5-(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 121
Table 121 provides 114 compounds of Formula I-A wherein R2 is 3,4-dichloro-5- (trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 122
Table 122 provides 114 compounds of Formula I-A wherein R2 is 3,5-bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 123
Table 123 provides 114 compounds of Formula I-A wherein R2 is 4-chloro-3,5- bis(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P.
Table 124
Table 124 provides 114 compounds of Formula I-A wherein R2 is 3-(trifluoromethyl)phenyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 125
Table 125 provides 114 compounds of Formula I-A wherein R2 is 2,6-dichloro-4-pyridyl, Al is N, A2 is CH, A3 is N, and Rl , Ga and Gb are as defined in Table P.
Table 126
Table 126 provides 114 compounds of Formula I-A wherein R2 is 2,6-bis(trifluoromethyl)-4-pyridyl, Al is N, A2 is CH, A3 is N, and Rl, Ga and Gb are as defined in Table P. Table P
Rl Ga and Gb
1 trifluoromethyl Gl
2 difluorochloromethyl Gl
3 difluoromethyl Gl
4 trifluoromethyl G2
5 difluorochloromethyl G2
6 difluoromethyl G2
7 trifluoromethyl G3
8 difluorochloromethyl G3
9 difluoromethyl G3
10 trifluoromethyl G4
11 difluorochloromethyl G4
12 difluoromethyl G4
13 trifluoromethyl G5
14 difluorochloromethyl G5
15 difluoromethyl G5
16 trifluoromethyl G6
17 difluorochloromethyl G6
18 difluoromethyl G6
19 trifluoromethyl G7
20 difluorochloromethyl G7
21 difluoromethyl G7
22 trifluoromethyl G8
23 difluorochloromethyl G8
24 difluoromethyl G8
25 trifluoromethyl G9
26 difluorochloromethyl G9
27 difluoromethyl G9
28 trifluoromethyl G10
29 difluorochloromethyl G10
30 difluoromethyl G10
31 trifluoromethyl Gi l
32 difluorochloromethyl Gi l
33 difluoromethyl Gi l
34 trifluoromethyl G12
35 difluorochloromethyl G12
36 difluoromethyl G12
37 trifluoromethyl G13
38 difluorochloromethyl G13
39 difluoromethyl G13
40 trifluoromethyl G14
41 difluorochloromethyl G14
42 difluoromethyl G14 43 trifluoromethyl G15
44 difluorochloromethyl G15
45 difluoromethyl G15
46 trifluoromethyl G16
47 difluorochloromethyl G16
48 difluoromethyl G16
49 trifluoromethyl G17
50 difluorochloromethyl G17
51 difluoromethyl G17
52 trifluoromethyl G18
53 difluorochloromethyl G18
54 difluoromethyl G18
55 trifluoromethyl G19
56 difluorochloromethyl G19
57 difluoromethyl G19
58 trifluoromethyl G20
59 difluorochloromethyl G20
60 difluoromethyl G20
61 trifluoromethyl G21
62 difluorochloromethyl G21
63 difluoromethyl G21
64 trifluoromethyl G22
65 difluorochloromethyl G22
66 difluoromethyl G22
67 trifluoromethyl G23
68 difluorochloromethyl G23
69 difluoromethyl G23
70 trifluoromethyl G24
71 difluorochloromethyl G24
72 difluoromethyl G24
73 trifluoromethyl G25
74 difluorochloromethyl G25
75 difluoromethyl G25
76 trifluoromethyl G26
77 difluorochloromethyl G26
78 difluoromethyl G26
79 trifluoromethyl G27
80 difluorochloromethyl G27
81 difluoromethyl G27
82 trifluoromethyl G28
83 difluorochloromethyl G28
84 difluoromethyl G28
85 trifluoromethyl G29
86 difluorochloromethyl G29
87 difluoromethyl G29
88 trifluoromethyl G30 „^
Figure imgf000027_0002
Compounds of formula I include at least one chiral centre and may exist as compounds of formula I* or compounds of formula I**. Compounds I* and I** are enantiomers if there is no other chiral center or epimers otherwise.
Figure imgf000027_0001
(I*) (I**)
Generally compounds of formula I** are more biologically active than compounds of formula I*. The invention includes mixtures of compounds I* and I** in any ratio e.g. in a molar ratio of 1 :99 to 99:1, e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio. In an enantiomerically (or epimerically) enriched mixture of formula I**, the molar proportion of compound I** compared to the total amount of both enantiomers is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Likewise, in enantiomerically (or epimerically) enriched mixture of formula I*, the molar proportion of the compound of formula I* compared to the total amount of both enantiomers (or epimerically) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Enantiomerically (or epimerically) enriched mixtures of formula I** are preferred. Each compound disclosed in Tables 1 to 126 represents a disclosure of a compound according to the compound of formula I* and a compound according to the compound of formula I**.
The compounds of the invention may be made by a variety of methods as shown in the following
Figure imgf000028_0001
In scheme 1 Ar stands for group A or group Al
Figure imgf000028_0002
wherein A1, A2, A3, A4, X1, R3, R4 and R5 are as defined for compounds of formula I.
1) Compounds of formula (IV) wherein Ar stands for group A or group Al can be prepared by reacting a compound of formula (III) with the vinyl compound of formula (II) optionally in the presence of a suitable solvent, for example NN-dimethylformamide, xylene, toluene, chlorobenzene or
dichlorobenzene. The reaction can be performed under microwave heating preferably at temperatures up to 200°C and preferably under neat conditions using a large excess of the compound of formula II (e.g. 40 equivalents). Vinyl compounds of formula (II) are commercially available or can be made by methods 0 known to a person skilled in the art. Compounds of formula (III) can be made by methods known to a person skilled in the art, as described in journal of Organic Chemistry (1981), 46(4), 771.
Scheme 2
Figure imgf000029_0001
2) Compounds of formula VI may be prepared from compounds of formula V by cleavage of the phthalimide protecting group (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience,New York, 1999, 564-566, 740-743.). Preferred reagents for this transformation are hydrazine or hydrazine hydrate in a suitable solvent (methanol, ethanol, tetrahydrofuran, toluene and others). Reaction temperature is in the range 0°C to 200°C, more preferably 25°C to 150°C. The reaction time is usually in the range O.lh to lOOh. Other methods employing for example methylamine, sodium hydroxide, lithium hydroxide, potassium hydroxide, ethylene diamine, methylhydrazine, ethanolamine and others or a two-step procedures may be used as well (S. E. Sen, S. L. Roach, Synthesis, 1995, 756- 758; J. O. Osby, M. G. Martin, B. Ganem, Tetrahedron Lett, 1984, 25, 2093-2096.)
Scheme 3
Figure imgf000029_0002
Compounds of formula (VIII) can be prepared by reacting a compound of formula (VII) wherein Rx is OH, Ci-Cealkoxy or CI, F or Br, with an amine of formula (VI) as shown in Scheme 3. When Rx is OH such reactions are usually carried out in the presence of a coupling reagent, such as Ν,Ν'- dicyclohexylcarbodiimide ("DCC"), l-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride ("EDC") or bis(2-oxo-3-oxazolidinyl)phosphonic chloride ("BOP-C1"), in the presence of a base, and optionally in the presence of a nucleophilic catalyst, such as hydroxybenzotriazole ("HOBT"). When Rx is CI, such reactions are usually carried out in the presence of a base, and optionally in the presence of a nucleophilic catalyst. It is possible to conduct the reaction in a biphasic system comprising an organic solvent, preferably ethyl acetate, and an aqueous solvent, preferably a solution of sodium hydrogen carbonate. When Rx is CpCealkoxy it is sometimes possible to convert the ester directly to the amide by 5 heating the ester and amine together in a thermal process. Suitable bases include pyridine, triethylamine, 4-(dimethylamino)-pyridine ("DMAP") or diisopropylethylamine (Hunig's base). Preferred solvents are NN-dimethylacetamide, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, ethyl acetate and toluene. The reaction is carried out at a temperature of from 0°C to 100°C, preferably from 15°C to 30°C, in particular at ambient temperature.
10
Sc
Figure imgf000030_0001
(xi) (xii) (|V)
In scheme 4 Ar stands for group A or group Al as defined in scheme 1.
15 4) Compounds of formula (XI) wherein Z1 is hydrogen or cyano or CpCgalkyl or aryl-Cr
C4alkylene-or Q-Cgalkylcarbonyl- or arylsulfonyl- or arylthio-, can be obtained by reacting an unsaturated ketone of formula (IX), with a sulfur nucleophile, such as thioacetic acid, hydrogen sulfide, sodium sulfide, ammonium sulfide, thiourea, benzylmercaptan, Sodium benzenethiosulfonate, potassium thiocyanate, sodium thiocyanate, sodium thiomethoxide or tert-butyl mercaptan as shown on Scheme 4.
20 Such reactions can be performed optionally in the presence of a base, such as sodium hydroxide, sodium ethoxide, sodium methoxide, sodium tert-butoxide or potassium hydroxide. Sometimes, such reations can also be performed in the presence of an acid, for example p-toluenesulfonic acid, hydrochloric acid, acetic acid, in a solvent, such as methanol, ethanol, NN-dimethylformamide, toluene, dichloromethane, ethyl acetate, acetonitrile or chlorobenzene or water, or mixtures thereof, at a temperature of from 0°C to
25 100°C, preferably from ambient temperature to 80°C. Such conditions are described, for example, in Journal of the American Chemical Society (1949), 71, 3554-5 or in Tetrahedron: Asymmetry (2003), 14(1), 113-117 and Journal of Organic Chemistry (1996), 61, 1986.
5) Compounds of formula (X) wherein Z3 is thiol or aryl substituted Ci-C8alkylsulfinyl-, can be made by reaction of the ketone of formula (IX) with an amine, such as triphenylmethanesulfenamide. 3Q
Such reactions are usually carried out in the presence of an acid or not, for example p-toluenesulfonic acid, hydrochloric acid, acetic acid, optionnally in the presence of a solvent, for example an alcohol, such as methanol or ethanol, or toluene, dichloromethane, water, or mixtures thereof. The reaction can be carried out in the presence or the absence of a dehydrating agent, such as anhydrous magnesium sulfate or molecular sieves. It can also be perfomed using a Dean Stark or Soxhlet apparatus that enables a constant removal of the water formed during the reaction. The reaction is carried out at a temperature of from 0°C to 100°C, preferably from 15°C to 30°C, in particular at ambient temperature.
6) Compounds of formula (XII) wherein Z2 is hydrogen or hydroxyl or d-Cgalkoxy- or Cp Cgalkylsulfonyloxy- or Ci-Cgarylsulfonyloxy- or aryl-Ci-C4alkylene-or aryl, can be made by reaction of the ketone of formula (XI) with an amine, such as hydroxylamine hydrochloride, methoxylamine or ammonia. Such reactions are carried out in the presence of a base, for example an organic base, such as triethylamine or sodium acetate, or an inorganic base, such as sodium hydrogen carbonate, optionally in the presence of a solvent, for example an alcohol, such as methanol or ethanol, or water, or mixtures thereof. Such reactions can also be carried out in the presence of an acid or not, for example p- toluenesulfonic acid, hydrochloric acid, acetic acid, optionnally in the presence of a solvent, for example an alcohol, such as methanol or ethanol, or toluene, dichloromethane, water, or mixtures thereof. The reaction can be carried out in the presence or the absence of a dehydrating agent, such as anhydrous magnesium sulfate or molecular sieves. It can also be perfomed using a Dean Stark or Soxhlet apparatus that enables a constant removal of the water formed during the reaction. The reaction is carried out at a temperature of from 0°C to 100°C, preferably from 15°C to 30°C, in particular at ambient temperature.
7) Compounds of formula (IV) can be obtained by cyclising a compound of formula (X) wherein Z3 is thiol. Such reactions are usually carried out in the presence of an acid or not, for example p- toluenesulfonic acid, optionnally in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene.The reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C. Alternatively, compounds of formula (IV) can be obtained by cyclising a compound of formula (X) wherein Z3 is aryl substituted Ci-Cgalkylsulfinyl-. Such reactions are usually carried out in the presence of an acid or not, for example p-toluenesulfonic acid,
trifluoroacetic acid or hydrochloric acid, optionnally in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene.The reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C. Such reactions usually involve first the deprotection of the thiol to give a compound of formula (X) wherein Z3 is thiol, followed by the cyclization.
8) Compounds of formula (IV) can be obtained from compound of formula (XII) wherein Z1 is hydrogen or cyano or CpCgalkyl or aryl-Ci-C4alkylene-or Ci-Cgalkylcarbonyl- or arylsulfonyl- or arylthio-, and Z2 is hydrogen or hydroxyl or d-Cgalkoxy- or Ci-Cgalkylsulfonyloxy- or d-
Cgarylsulfonyloxy- or aryl-Ci-C4alkylene-or aryl. Such reactions usually involve the deprotection of Z1 and ofZ2 or of both groups. The reaction can then involve the following intermediates: „ Λ
Figure imgf000032_0001
(XI I I) (XIV) (XV)
Depending on the nature of Z1 and Z2, the deprotection conditions are different and can be made by methods known to a person skilled in the art or as described in T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 564-566, 740-743.
9) Compounds of formula (IV) can be obtained from compound of formula (XIII) from an oxidation step. Such reactions are usually carried out in the presence of an oxidant, for example iodine, bromine, thionyl chloride, Bis(trifluoroacetoxy)iodobenzene; The reaction can be carried out in the presence of an acid or not, such as trifluoroacetic acid or acetic acid, optionnally in the presence of a solvent, for example dichloroethane, dimethylsulfoxide, NN-dimethylformamide, methanol, ethanol, toluene, dichloromethane, ethyl acetate or chlorobenzene.The reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C. Such transformations, including reaction conditions and suitable catalyst, are described in Journal of the Chemical Society, Perkin Transactions 1 : Organic and Bio-Organic Chemistry (1972-1999) (1985), (1), 153-7 and Organic Letters (2006), 8(21), 481 1 - 4813. Similarly, compounds of formula (IV) can be obtained from a compound of formula (XIV) wherein Z1 is arylsulfonyl- or arylthio-, by an oxidation step, are described in Journal of Organic Chemistry (1990), 55(13), 4156-62.
10) Compounds of formula (IV) can be obtained from compound of formula (XV) wherein Z2 is Cr C8alkoxy-. Such reactions are usually carried out in the presence of a copper (I) reagent, such copper-3- methylsalicylate. The reaction can be carried out in the presence of a solvent, for example dichloroethane, dimethylsulfoxide, NN-dimethylformamide, methanol, ethanol, toluene, dichloromethane, ethyl acetate or chlorobenzene.The reaction is carried out at a temperature of from 0°C to 200°C, preferably from 25°C to 100°C, or under microwave heating conditions. Such transformations are described in Journal of the American Chemical Society (201 1), 133, 6403-6410.
1 1) Alternatively, compounds of formula (IV) can be obtained directly from a compound of formula (XIV) wherein Z1 is hydrogen. Such reactions are usually carried out in the presence chloramines, formed in situ from ammonia and chlorine or sodium hypochlorite or hypochlorous acid, optionnally in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene.The reaction is carried out at a temperature of from -80°C to 40°C, preferably below - 40°C.
12) Alternatively, compounds of formula (IV) can be obtained directly from a compound of formula (XI) wherein Z1 is halogen, cyano, arylsulfonyl- or arylthio-. Such reactions are usually carried out in the presence ammonia, optionnally in the presence of a solvent, for example dichloroethane, tetrahydrofuran, ^ methanol, ethanol, toluene, dichloromethane or chlorobenzene.The reaction is carried out at a temperature of from -80°C to 80°C.
13) Alternatively, compounds of formula (IV) can be obtained directly from a compound of formula (XI) wherein Z1 is aryl-Ci-C4alkylene. Such reactions are usually carried out in two steps- The first one involves the treatment of a compound of formula (XI) wherein Z1 is aryl-Ci-C4alkylene by a suitable oxidant, such as sulfuryl chloride or chlorine, in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, dichloromethane or chlorobenzene, to provide a compound of formula (XI) wherein Z1 is chlorine. The second step then involves the treatment a compound of formula (XI) wherein Z1 is chlorine by an ammonia source, such as ammonia or ammonium bromide in the presence of a base, in the presence of a solvent, for example dichloroethane, methanol, ethanol, toluene, tetrahydrofuran, dichloromethane or chlorobenzene.Both steps are usually carried out at a temperature of from -80°C to 80°C.
14) Alternatively, compounds of formula (IV) can be obtained directly from a compound of formula (XI) wherein Z1 is hydrogen. Such reactions are usually carried out in the presence of a suitable nitrogen electrophile, such as Hydroxylamine-O-sulfonic acid. Such reactions are carried out in the presence of a base, for example an organic base, such as triethylamine or sodium acetate, or an inorganic base, such as sodium hydrogen carbonate, sodium hydroxide or potassium hydroxide optionally in the presence of a solvent, for example tetrahydrofuran, toluene, an alcohol, such as methanol or ethanol, or water, or mixtures thereof. The reaction is carried out at a temperature of from -80°C to 80°C.
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 compounsd of the invention 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. Compositions comprising the compound of formula I may be used on ornamental garden plants (e.g. flowers, shrubs, broad-leaved trees or evergreens), e.g. to control aphids, whitefly, scales, meelybug, beetles and caterpillars. Compositions comprising the compound of formula I may be used on garden plants (e.g. flowers, shrubs, broad-leaved trees or evergreens), on indoor plants (e.g. flowers and shrubs) and on indoor pest e.g. to control aphids, whitefly, scales, meelybug, beetles and caterpillars.
Furthermore, the compounds of the invention may be effective against harmful insects, without substantially imposing any harmful side effects to cultivated plants. Application of the compounds of the invention may increase the harvest yields, and may improve the quality of the harvested material. 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.
Examples of pest species which may be controlled by the compounds of formula (I) include: coleopterans, for example, Callosobruchus chinensis, Sitophilus zeamais, Tribolium castaneum,
Epilachna vigintioctomaculata, Agriotes fuscicollis, Anomala rufocuprea, Leptinotarsa decemlineata, Diabrotica spp., Monochamus alternatus, Lissorhoptrus oryzophilus, Lyctus bruneus, Aulacophora femoralis; lepidopterans, for example, Lymantria dispar, Malacosoma neustria), Pieris rapae,
Spodoptera litura, Mamestra brassicae, Chilo suppressalis), Pyrausta nubilalis, Ephestia cautella, Adoxophyes orana, Carpocapsa pomonella, Agrotisfucosa, Galleria mellonella, Plutella maculipennis, Heliothis virescens, Phyllocnistis citrella; hemipterans, for example, Nephotettix cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspis yanonensis, Myzus persicas, Aphis pomi, Aphis gossypii, Rhopalosiphum pseudobrassicas, Stephanitis nashi, Nezara spp., Trialeurodes vaporariorm, Psylla spp.; thysanopterans, for example, Thrips palmi, Franklinella occidental; orthopterans, for example, Blatella germanica, Periplaneta americana, Gryllotalpa Africana, Locusta migratoria migratoriodes ; isopterans, for example, Reticulitermes speratus, Coptotermes formosanus; dipterans, for example, Musca domestica, Aedes aegypti, Hylemia platura, Culex pipiens, Anopheles sinensis, Culex tritaeniorhynchus, Liriomyza trifolii; acari, for example, Tetranychus cinnabarinus, Tetranychus urticae, Panonychus citri, Aculops pelekassi, Tarsonemus spp. ; nematodes, for example, Meloidogyne incognita, Bursaphelenchus lignicolus Mamiya et Kiyohara, Aphelenchoides besseyi, Heterodera glycines, Pratylenchus spp..
Examples of further pest species which may be controlled by the compounds of formula (I) include: 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., PopilUa japonica, Premnotrypes spp., PsylUodes chrysocephala, Ptinus spp., Rhizobius ventralis, 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., Bibio 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, Arion 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., Loa Loa, 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; ft 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 coffeae, 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 vulgar e, 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.
In particular, the compounds of the invention may be used to control the following pest spcies: 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
Figure imgf000037_0001
eelworm), Trichostrongylus spp. (gastro intestinal nematodes) and Deroceras reticulatum (slug).
The compound of formula I 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, cucurbits and pulses (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 for pest control on various plants, including soybean, corn, sugarcane, alfalfa, brassicas, oilseed rape (e.g. canola), potatoes (including sweet potatoes), cotton, rice, coffee, citrus, almonds, fruiting vegetables, cucurbits and pulses (e.g. tomatoes, pepper, chili, eggplant, cucumber, squash etc.), tea, bulb vegetables (e.g. onion, leek etc.), grapes, pome fruit (e.g. apples, pears etc.), stone fruit (e.g. pears, plums etc.), and cereals.
The compounds of the invention may be used on soybean to control, for example, Elasmopalpus Ugnosellus, Diloboderus abderus, Diabrotica speciosa, Trialeurodes spp., Bemisia spp., aphids, Sternechus subsignatus, Formicidae, Agrotis ypsilon, Julus spp., Murgantia spp., Halyomorpha spp., Thyanta spp., Megascelis ssp., Procornitermes ssp., Gryllotalpidae, Nezara viridula, Piezodorus spp., Acrosternum spp., Neomegalotomus spp., Cerotoma trifurcata, Popil a japonica, Edessa spp., Liogenys fuscus, Euschistus heros, stalk borer, Scaptocoris castanea, phyllophaga spp., Migdolus spp.,
Pseudoplusia includens, Anticarsia gemmatalis, Epinotia spp., Rachiplusia spp., Spodoptera spp., Bemisia tabaci, Tetranychus spp., Agriotes spp. , Euschistus spp.. The compounds of the invention are preferably used on soybean to control Diloboderus abderus, Diabrotica speciosa, Trialeurodes spp., Bemisia spp., Nezara viridula, Piezodorus spp., Acrosternum spp., Cerotoma trifurcata, PopilUa japonica, Euschistus heros, Scaptocoris castanea, phyllophaga spp., Migdolus spp., Agriotes spp., Euschistus spp..
The compounds of the invention may be used on corn to control, for example, Euschistus heros, Euschistus spp., Dichelops furcatus, Diloboderus abderus, Thyanta spp., Elasmopalpus Ugnosellus, Halyomorpha spp., Spodoptera frugiperda, Nezara viridula, Cerotoma trifurcata, PopilUa japonica, Agrotis ypsilon, Diabrotica speciosa, aphids, Heteroptera, Procornitermes spp., Scaptocoris castanea, Formicidae, Julus ssp., Dalbulus maidis, Diabrotica virgifera, Diabrotica spp., Mods latipes, Bemisia tabaci, heliothis spp., Tetranychus spp., thrips spp., phyllophaga spp., Migdolus spp., scaptocoris spp., Liogenys fuscus, Spodoptera spp., Ostrinia spp., Sesamia spp., wireworms, Agriotes spp., Halotydeus destructor. The compounds of the invention are preferably used on corn to control Euschistus heros,
Euschistus spp., Dichelops furcatus, Diloboderus abderus, Nezara viridula, Cerotoma trifurcata, PopilUa japonica, Diabrotica speciosa, Diabrotica virgifera, Diabrotica spp., Tetranychus spp., Thrips spp., Phyllophaga spp., Migdolus spp., Scaptocoris spp., Agriotes spp..
The compounds of the invention may be used on sugar cane to control, for example,
Sphenophorus spp., termites, Migdolus spp., Diloboderus spp., Telchin licus, Diatrea saccharalis, Mahanarva spp., Mealybugs.
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 spp., Geocoris spp., Lygus hesperus, Lygus Uneolaris, Spissistilus spp., Spodoptera spp., Aphids, Trichoplusia ni. The compounds of the invention are preferably used on alfalfa to control Hypera brunneipennis, Hypera postica, Empoasca solana, Epitrix spp., Lygus hesperus, Lygus Uneolaris, 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., - jo -
Empoasca spp., thrips spp., Delia spp., Murgantia spp., Trialeurodes spp., Bemisia spp., Microtheca spp., Aphids.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, Halotydeus destructor, 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., Aphids, wireworms. 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, Trialeurodes spp., Aphids, Lygus spp., phyllophaga spp., Scaptocoris spp., Austroasca viridigrisea, Creontiades spp., Nezara spp., Piezodorus spp., Halotydeus destructor, Oxycaraenus hyalinipennis, Dysdercus cingulatus. 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, Scotinophara spp., Nephotettix malayanus, Nephotettix nigropictus, Nephotettix parvus, Nephottetix virescens, Nephotettix spp., Mealybugs, Sogatella furcifera, Nilaparvata lugens, Orseolia spp., Cnaphalocrocis medinalis, Marasmia spp., Stenchaetothrips biformis, Thrips spp., Hydrellia philippina, Grasshoppers, Pomacea canaliculata, Scirpophaga innotata, Chilo suppressalis, Chilo auricilius, Chilo polychrysus, Sesamia inferens, Laodelphax striatellus, Nymphula depunctalis, Oulema oryzae, Stinkbugs. The compounds of the invention are preferably used on rice to control Leptocorisa spp., Lissorhoptrus spp., Oebalus pugnax, Nephotettix malayanus, Nephotettix nigropictus, Nephotettix parvus, Nephottetix virescens, Nephotettix spp., Sogatella furcifera, Stenchaetothrips biformis, Thrips spp., Hydrellia philippina, Grasshoppers, Pomacea canaliculata, Scirpophaga innotata, Chilo suppressalis, Chilo polychrysus, Oulema oryzae.
The compounds of the invention may be used on coffee to control, for example, Hypothenemus
Hampei, Perileucoptera Coffeella, Tetranychus spp., Brevipalpus spp., Mealybugs. 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., Aphids, Hardscales, Softscales, Mealybugs. 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 vegetables, cucurbits and pulses, 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., Tuta absoluta, Liriomyza spp., Bemisia tabaci, Trialeurodes spp., Aphids, Paratrioza spp., Frankliniella occidentalis , Frankliniella spp., Anthonomus spp., Phyllotreta spp., Amrasca spp., Epilachna spp., Halyomorpha spp., Scirtothrips spp., Leucinodes spp., Neoleucinodes spp. Maruca spp., Fruit flies, Stinkbugs, Lepidopteras, Coleopteras. The compounds of the invention are preferably used on fruiting vegetables, cucurbits and pulses, 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., 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, Tetranychus spp..T e compounds of the invention are preferably 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., Eupoecilia ambiguella, Frankliniella spp., Thrips spp., Tetranychus spp., Rhipiphorothrips Cruentatus, Eotetranychus Willamettei, Erythroneura Elegantula, Scaphoides spp., Scelodonta strigicollis, Mealybugs. 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, pears etc., to control, for example, Cacopsylla spp., Psylla spp., Panonychus ulmi, Cydia pomonella, Lepidopteras, Aphids, Hardscales, Softscales. The compounds of the invention are preferably used on pome fruit, including apples, pears 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., Aphids, Hardscales, Softscales, Mealybugs. The compounds of the invention are preferably used on stone fruit to control Scirtothrips spp., Thrips spp., Frankliniella spp., Tetranychus spp..
The compounds of the invention may be used on cereals to control, for example, Aphids, Stinkbugs, earthmites, Eurygaster integriceps, Zabrus tenebrioides, Anisoplia austriaca, Chaetocnema aridula, Phyllotreta spp., Oulema melanopus, Oscinella spp., Delia spp., Mayetiola spp., Contarinia spp., Cephus spp., Steneotarsonemus spp., Apamea spp..
In another embodiment compounds of formula I may be used on rice to control Baliothrips biformis (Thrips), Chilo spp. (e.g. Chilo polychrysus (Dark headed striped borer), Chilo suppressalis 4Q
(Rice stemborer), Chilo indicus (Paddy stem borer), Chilo polychrysus (Dark-headed rice borer), Chilo suppressalis (Stripe stem borer)), Cnaphalocrocis medinalis (Rice leaf folder), Dicladispa armigera (Hispa), Hydrellia philipina (Rice whorl-maggot), Laodelphax spp. (Smaller brown planthopper) (e.g. Laodelphax striatellus ), Lema oryzae (Rice leaf eetle), Leptocorsia acuta (Rice bug), Leptocorsia oratorius (rice bug), Lissorhoptrus oryzophilus (rice water weevil), Mythemina separata (armyworm), Nephottetix spp. (Green leafhopper ) (e.g. Nephotettix cincticeps, Nephotettix malayanus, Nephotettix nigropictus, Nephotettix parvus, Nephottetix virescens), Nilaparvata lugens (Brown Planthopper), Nymphula depunctalis (Rice caseworm), Orseolia oryzae (Rice Gall midge), Oulema oryzae (Rice leafbeetle), Scirpophaga incertulas (Yellow Stemborer), Scirpophaga innotata (White Stemborer), Scotinophara coarctata (Rice black bug), Sogaella frucifera (White-backed planthopper),
Steneotarsonemus spinki.
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 web worms, 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.
The compounds of formula (I) may be used for soil applications, including as a seed application, to target at least the following: sucking pests such as aphids, thrips, brown plant hopper (e.g. on rice), sting bugs, white flies (e.g. on cotton and vegetables), mites; on soil pests such as corn root worm, wireworms, white grubs, zabrus, termites (e.g. on sugar cane, soy, pasture), maggots, cabbage root fly, red legged earth mite; on lepidoptera, such as spodoptera, cutworms, elasmoplpus , plutella (e.g. brassica), stem borers, leaf miners, flea beetle, Sternechus; on nematicides, such as Heterodera glycines (e.g. on soybean), Pratylenchus brachyurus (e.g. on corn), P. zeae (e.g. oncorn), P. penetrans (e.g. on corn), Meloidogyne incognita (e.g. on vegetables), Heterodera schachtii (e.g. on sugar beet), Rotylenchus reniformis (e.g. on cotton), Heterodera avenae (e.g. on cereals), Pratylenchus neglectus (e.g. on cereals), thornei (e.g. on cereals).
The compounds of formula (I) may be used for seed applications at least on the following: soil grubs for corn, soybeans, sugarcane: Migdolus spp; Phyllophaga spp.; Diloboderus spp; Cyclocephala spp; Lyogenys fuscus; sugarcane weevils: Sphenophorus levis & Metamasius hemipterus; termites for soybeans, sugarcane, pasture, others: Heterotermes tenuis; Heterotermes longiceps; Cornitermes cumulans; Procornitermes triacifer ; Neocapritermes opacus; Neocapritermes parvus; corn root worms for corn and potatoes: Diabrotica spp., seed Maggot: Delia platura; soil stinkbugs: Scaptocoris castanea; wireworms: Agriotes spp; Athous spp Hipnodes bicolor; Ctenicera destructor; Limonius canu; Limonius californicus; rice water weevil: Lissorhoptrus oryzophilus; Red Legged earth mites: Halotydeus destructor.
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 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, 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®.
The compounds of the invention may be applied to plant parts. Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaf, flower and root, examples which may be mentioned being leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. The plant parts also include harvested material, and vegetative and generative propagation material, for example cuttings, tubers, rhizomes, offshoots and seeds. Treatment according to the invention of the plants and plant parts with the active compounds is carried out directly or by allowing the compounds to act on their surroundings, habitat or storage space by the customary treatment methods, for example by immersion, spraying, evaporation, fogging, scattering, painting on, injecting and, in the case of propagation material, in particular in the case of seed, also by applying one or more coats.
Compounds of formula I may be used on transgenic plants (including cultivars) obtained by genetic engineering methods and/or by conventional methods. These are understood as meaning plants having novel properties ("traits") which have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. Depending on the plant species or plant cultivars, their location and growth conditions (soils, climate, vegetation period, diet), the treatment according to the invention may also result in superadditive "synergistic") effects.
Thus, for example, reduced application rates and/or a widening of the activity spectrum and/or an increase in the activity of the substances and compositions which can be used according to the invention, better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, higher quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products are possible, which exceed the effects which were actually to be expected.
The preferred transgenic plants or plant cultivars which are to be treated according to the invention include all plants which, by virtue of the genetic modification, received genetic material which imparts particularly advantageous, useful traits to these plants. Examples of such traits are better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, higher quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products.
Further and particularly emphasized examples of such traits are a better defence of the plants against animal and microbial pests, such as against insects, mites, phytopathogenic fungi, bacteria and/or viruses, and also increased tolerance of the plants to certain herbicidally active compounds.
Examples of transgenic plants which may be mentioned are the important crop plants, such as cereals (wheat, rice), maize, soybean, potatoes, sugar beet, tomatoes, peas and other vegetable varieties, cotton, tobacco, oilseed rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes).
Compounds of formula I may be used on transgenic plants that are capable of producing one or more pesticidal proteins which confer upon the transgenic plant tolerance or resistance to harmful pests, e.g. insect pests, nematode pests and the like. Such pesticidal proteins include, without limitation, Cry proteins from Bacillus thuringiensis CrylAb, CrylAc, CrylF, Cry2Ab, Cry2Ae, Cry3A, Cry3Bb, or Cry9C; engineered proteins such as modified Cry3A ( US Patent 7,030,295) or CrylA.105; or vegetative insecticidal proteins such as Vipl, Vip2 or Vip3. A full list of Bt Cry proteins and VIPs useful in the invention can be found on the worldwide web at Bacillus thuringiensis Toxin Nomenclature Database maintained by the University of Sussex {see also, Crickmore et al. (1998) Microbiol. Mol. Biol. Rev. 62:807-813). Other pesticidal proteins useful in the invention include proteins of bacteria colonizing nematodes, e.g. Photorhabdus spp. or Xenorhabdus spp.; toxins produced by animals, such as scorpion ^ toxins, arachnid toxins, wasp toxins, or other insect-specific neurotoxins; toxins produced by fungi, such Streptomycetes toxins, plant lectins, such as pea or barley lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin or papain inhibitors; ribosome- inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-IDP-glycosyl -transferase, cholesterol oxidases, ecdysone inhibitors or HMG-CoA-reductase; ion channel blockers, such as blockers of sodium or calcium channels; juvenile hormone esterase; diuretic hormone receptors (helicokinin receptors); stilben synthase, bibenzyl synthase, chitinases or glucanases. Further examples of such pesticidal proteins or transgenic plants capable of synthesizing such proteins are disclosed, e.g., in EP-A 374753, WO 93/007278, WO 95/34656, EP-A 427529, EP-A 451878, WO 03/18810 and WO 03/52073. The methods for producing such transgenic plants are generally known to the person skilled in the art and some of which are commercially available such as Agrisure®CB (PI) (corn producing CrylAb), Agrisure®RW (P2) (corn producing mCry3A), Agrisure® Viptera (P3) (corn hybrids producing Vip3Aa); Agrisure300GT (P4) (corn hybrids producing CrylAb and mCry3A); YieldGard® (P5) (corn hybrids producing the CrylAb protein), YieldGard® Plus (P6) (corn hybrids producing CrylAb and Cry3Bbl), Genuity® SmartStax® (P7) (corn hybrids with CrylA.105, Cry2Ab2, CrylF, Cry34/35, Cry3Bb) ; Herculex® I (P8) (corn hybrids producing CrylFa) and Herculex®RW (P9) (corn hybrids producing Cry34Abl, Cry35Abl and the enzyme Phosphinothricin-N-Acetyltransferase [PAT]) ; NuCOTN®33B (P10) (cotton cultivars producing CrylAc), Bollgard®I (PI 1) (cotton cultivars producing CrylAc), Bollgard®II (P12) (cotton cultivars producing CrylAc and Cry2Ab2) and VIPCOT® (P13) (cotton cultivars producing a Vip3Aa). Soybean Cyst Nematode resistance soybean (SCN® - Syngenta (PI 4)) and soybean with Aphid resistant trait (AMT® (PI 5)) are also of interest.
Further examples of such transgenic crops are:
1. Btll Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (PI 6). 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 CrylA(b) toxin. Btl 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Btl 76 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (PI 7). 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 CrylA(b) 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 (PI 8). Maize which has been rendered insect-resistant by transgenic expression of a modified CrylllA toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-D-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 (P19). MON 863 expresses a CrylllB(bl) 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. (P20)
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-l 160 Brussels, Belgium, registration number C/NL/00/10. (P21) 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 (P22). Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 χ 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 CrylA(b) toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
Further examples of transgenic plants, and of very high interest, are those carrying traits conferring resistance to 2.4D (e.g. Enlist®) (e.g. WO 2011066384) (P23), glyphosate (e.g. Roundup Ready® (P24), Roundup Ready 2 Yield® (P25)), sulfonylurea (e.g. STS®) (P26), glufosinate (e.g.
Liberty Link® (P27), Ignite® (P28)), Dicamba (P29) (Monsanto), HPPD tolerance (P30) (e.g.
isoxaflutole herbicide) (Bayer CropScience, Syngenta). Double or triple stacks of any of the traits described here are also of interest, including glyphosate and sulfonyl-urea tolerance ((e.g. Optimum GAT®) (P31), plants stacked with STS® and Roundup Ready® (P32) or plants stacked with STS® and Roundup Ready 2 Yield® (P33)), dicamba and glyphosate tolerance (P34) (Monsanto). Of particular interest are soybean plants carrying trains conferring resistance to 2.4D (e.g. Enlist®), glyphosate (e.g. Roundup Ready®, Roundup Ready 2 Yield®), sulfonylurea (e.g. STS®), glufosinate (e.g. Liberty Link®, Ignite®), Dicamba (Monsanto) HPPD tolerance (e.g. isoxaflutole herbicide) (Bayer CropScience, Syngenta). Double or triple stack in soybean plants of any of the traits described here are also of interest, including glyphosate and sulfonyl-urea tolerance (e.g. Optimum GAT®, plants stacked with STS® and Roundup Ready® or Roundup Ready 2 Yield®), dicamba and glyphosate tolerance (Monsanto).
Transgenic crops of insect-resistant plants are also described in BATS (Zentrum fur Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http://bats.ch).
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 O.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 O.OOlg 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 C8-Ci0 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. - 4o -
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' opropyl- and tri-wopropyl-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. Examples of suitable pesticides include the following:
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. Examples of suitable pesticides include the following:
a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin and gamma cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, S-bioallethrin, fenfluthrin, prallethrin, acrinathirin, etofenprox or
5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane 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; 5Q 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, diafenthiuron, lufeneron, novaluron, noviflumuron or chlorfluazuron;
e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin;
f) Pyrazoles, such as tebufenpyrad, tolfenpyrad, ethiprole, pyriprole, fipronil, and fenpyroximate;
g) Macrolides, such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad, azadirachtin, milbemectin, lepimectin or spinetoram;
h) Hormones or pheromones;
i) Organochlorine compounds, such as endosulfan (in particular alpha-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, nitenpyram, dinotefuran, thiamethoxam, clothianidin, or nithiazine;
m) Diacylhydrazines, such as tebufenozide, chromafenozide or methoxyfenozide;
n) Diphenyl ethers, such as diofenolan or pyriproxifen;
o) Pyrazolines such as Indoxacarb or metaflumizone;
p) Ketoenols, such as Spirotetramat, spirodiclofen or spiromesifen;
q) Diamides, such as flubendiamide, chlorantraniliprole (Rynaxypyr®) or cyantraniliprole;
r) Essential oils such as Bugoil® - (Plantlmpact); or
s) a comopund selected from buprofezine, flonicamid, acequinocyl, bifenazate, cyenopyrafen, cyflumetofen, etoxazole, flometoquin, fluacrypyrim, fluensulfone, flufenerim, flupyradifuone, harpin, iodomethane, dodecadienol, pyridaben, pyridalyl, pyrimidifen, flupyradifurone, 4-[(6-Chloro-pyridin-3- ylmethyl)-(2,2-difluoro-ethyl)-amino]-5H-furan-2-one (DE 102006015467), CAS: 915972-17-7
(WO 2006129714; WO2011/147953; WO2011/147952), CAS: 26914-55-8 (WO 2007020986), chlorfenapyr, pymetrozine, sulfoxaflor and pyrifluqinazon.
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). Examples of fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide (SSF-129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-l -sulfonamide,
a-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-y-butyrolactone, 4-chloro-2-cyano-N,N-dimethyl-5-/?- tolylimidazole-1 -sulfonamide (IKF-916, cyamidazosulfamid), 3-5-dichloro-N-(3-chloro-l-ethyl-l -methyl-
2- oxopropyl)-4-methylbenzamide (RH-7281 , zoxamide), N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-
3- carboxamide (ΜΟΝ65500), N-(l -cyano-1 ,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide (AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, acibenzolar (CGA245704) (e.g. acibenzolar-S-methyl), alanycarb, aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, biloxazol, bitertanol, bixafen, blasticidin S, boscalid, bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulfate, copper tallate and Bordeaux mixture, cyclufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulfide 1,1 '-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb, difenoconazole, difenzoquat, diflumetorim,
OjO-di-wo-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol, ethyl-(Z)-N-benzyl-N-([methyl(methyl-thioethylideneamino- oxycarbonyl)amino]thio)- -alaninate, etridiazole, famoxadone, fenamidone (RPA407213), fenarimol, fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, fluopyram,
fluoxastrobin, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, fluxapyroxad, folpet, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbamate, isoprothiolane, isopyrazam, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY248908, mancozeb, mandipropamid, maneb, mefenoxam, metalaxyl, mepanipyrim, mepronil, metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothal-wopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, penthiopyrad, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxinD, polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, propionic acid, prothioconazole, pyrazophos, pyrifenox, pyrimethanil, pyraclostrobin, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinomethionate, quinoxyfen, quintozene, sedaxane, sipconazole (F-155), sodium pentachlorophenate, spiroxamine, streptomycin, sulfur, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate -methyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, zineb and ziram, N- [9 -(dichloromethylene) -1,2,3,4 -tetrahydro- 1 ,4-methanonaphthalen-5 -yl] -3 -(difluoromethyl) - 1 -methyl- 1 H-pyrazole-4-carboxamide [1072957-71 -1], 1 -methyl-3 -difluoromethyl- 1 H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-l-methyl-indan-4-yl)-amide, and l -methyl-3-difluoromethyl-4H-pyrazole- 4-carboxylic acid [2-(2,4-dichloro-phenyl)-2-methoxy-l -methyl-ethyl] -amide.
In addition, biological agents may be included in the composition of the invention e.g. Baciullus species such as Bacillus firmus, Bacillus cereus, Bacillus subtilis, and Pasteuria species such as Pasteuria penetrans and Pasteuria nishizawae. A suitable Bacillus firmus strain is strain CNCM 1-1582 which is commercially available as BioNem™. A suitable Bacillus cereus strain is strain CNCM 1-1562. Of both Bacillus strains more details can be found in US 6,406,690. Other biological organisms that may be included in the compositions of the invention are bacteria such as Streptomyces spp. such as S.
avermitilis, and fungi such as Pochonia spp. such as P. chlamydosporia. Also of interest are Metarhizium spp. such as M. anisopliae; Pochonia spp. such as P. chlamydosporia.
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.
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, Buprofezine 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. c r
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When used in combination with other active ingredients, the compounds of the invention are preferably used in combination with the following: 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 ; more preferably, 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; even more preferably 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 .
Examples of ratios of a compound of formula I combined with any additional active ingredient 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 WO 03/024222.
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. - j o -
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), cultured fish, honeybees. 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.
By controlling these pests 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. Also, controlling parasites may help to prevent the transmittance of infectious agents, the term "controlling" referring to the veterinary field, meaning that the active compounds are effective in reducing the incidence of the respective parasite in an animal infected with such parasites to innocuous levels, e.g. the active compound is effective in killing the respective parasite, inhibiting its growth, or inhibiting its proliferation.
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. and protozoae, such as coccidia).
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 , Ancylostoma,
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, Strongy ides, 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 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).
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,
Trombiculalpha alphalfreddugesi.
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 compounds of the invention may also be effective against ectoparasites, e.g. 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 include e.g. 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).
Examples of species of animal health pesets include those 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., SimuUum 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, Aedes albopictus, Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis, Calliphora
erythrocephala, Chrysozona pluvialis, Culex quinquef as ciatus, Culex pipiens, Culex tarsalis, Fannia canicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipula paludosa, Lucilia cuprina, Lucilia sericata, SimuUum 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., RailUetia 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., Omithocheyletia 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; Gasterophilus spp., Stomoxys spp., Trichodectes spp., Rhodnius spp., Ctenocephalides canis, Cimx lecturius,
Ctenocephalides felis, Lucilia cuprina; examples of acari include Ornithodoros spp., Ixodes spp., Boophilus spp..
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; or 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.
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 r c
- 65 - 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 , ,
- 66 - 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).
The following Examples illustrate, but do not limit, the invention.
The following abbreviations were used in this section: DMF: dimethylformamide; THF: tetrahydrofuran; EtOAc : ethyl acetate; s = singlet; bs = broad singlet; d = doublet; dd = double doublet; dt = double triplet; t = triplet, tt = triple triplet, q = quartet, sept = septet; m = multiplet; Me = methyl; Et = ethyl; Pr = propyl; Bu = butyl; M.p. = melting point; RT = retention time, [M+H]+ = molecular mass of the molecular cation, [M-H]" = molecular mass of the molecular anion.
The following Examples illustrate, but do not limit, the invention.
The following abbreviations were used throughout this section: s = singlet; bs = broad singlet; d = doublet; dd = double doublet; dt = double triplet; t = triplet, tt = triple triplet, q = quartet, sept = septet; m = multiplet; Me = methyl; Et = ethyl; Pr = propyl; Bu = butyl; RT = retention time; MH = molecular cation.
Preparation of tert-butyl N-[5-r4.4.4-trifluoro-3-f3.4.5-trichlorophenyl but-2-enoyllindan-l-yllcarbamate
Figure imgf000068_0001
To a solution of tert-butyl N-(5-acetylindan-l-yl)carbamate (2 g) and 2,2,2-trifluoro-l-(3,4,5- trichlorophenyl)ethanone (2.21 g) in anhydrous acetonitrile (10 mL) was added under argon potassium carbonate (50 mg) in two portions (25mg/lh) and the reaction mixture was refluxed using a Dean-Stark device. Fresh anhydrous acetonitrile was continuously added to keep the same volume of solvent. After 2.5hours, the heating was stopped, water was added and the solution was extracted with ethyl acetate. The organic phase was washed two times with water then they were dried over magnesium sulfate, filtered and evaporated under vacuo. The residue was purified by chromatography on silica gel (eluent:
cyclohexane / ethyl acetate) to give
tert-butyl N-[5-[4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl]indan-l -yl]carbamate (3.88 g).
lH NMR (CDC13, 400MHz): δ = 7.64 - 7.74 (m, 2 H), 7.38 - 7.46 (m, 2 H), 7.30 (s, 2 H), 5.22 (m, 1 H), 4.74 (m, 1 H), 2.93 - 3.07 (m, 1 H), 2.80 - 2.93 (m, 1 H), 2.54 - 2.73 (m, 1 H), 1.82 (m, 1 H), 1.45 - 1.54 ppm (s, 9 H).
Preparation of tert-butyl N-r6-r5-(3,4,5-trichlorophenyl -5-(trifluoromethyl -4H-isothiazol-3-yl1indan-l - l"|carbamate
Figure imgf000068_0002
To tert-butyl N-[5-[4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl]indan-l-yl]carbamate (1 g) was added thioacetic acid (6 eq.) under argon, at room temperature, followed by 3 drops of triethylamine.
After a few minutes more thioacetic acid (2.5 mL) were added, followed by dichloromethane (2 mL). The solution was stirred at room temperature for 80 minutes then more triethylamine (20μί) and the solution was stirred overnight at room temperature and was then taken in isolute for purification by
chromatography on silica gel (eluent: cyclohexane/dichloromethane) to give tert-butyl N-[6-[4,4,4- trifluoro-3-sulfanyl-3-(3,4,5-trichlorophenyl)butanoyl]indan-l -yl]carbamate (1.02g) slightly impure that was used as such in the next step. To a stirred solution of tert-butyl N-[6-[4,4,4-trifluoro-3-sulfanyl-3-(3,4,5- trichlorophenyl)butanoyl]indan-l-yl]carbamate (1.02 g) in a minimum of tetrahydrofuran (ca 1 mL) was added hydroxylamine-O-sulfonic acid (2 eq.) followed by a solution of potassium hydroxide (500 mg in 31 mL of water) at 0°C. After stirring at room temperature for 10 minutes, the mixture was quenched by addition of a solution of hydrochloric acid (IN), diluted with ethyl acetate, and washed with brine. The collected organic phases were dried over magnesium sulfate, filtered and the filtrate was evaporated under vacuo. The residue was purified twice by chromatography on silica gel (eluent: cyclohexane/ethyl acetate) to give tert-butyl N-[6-[5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l - yl]carbamate (303 mg).
lU NMR (CDC13, 400MHz): δ =7.57 - 7.65 (m, 2 H), 7.46 (s, 2 H), 7.38 (d, J=7.7 Hz, 1 H), 5.21 (m, 1 H), 4.73 (m, 1 H), 4.21 (dd, J=17.4, 1.3 Hz, 1 H), 3.86 (d, J=17.6 Hz, 1 H), 2.98 (dd, J=8.8, 2.9 Hz, 1 H), 2.81 - 2.94 (m, 1 H), 2.51 - 2.72 (m, 1 H), 1.82 (dd, J=12.8, 8.4 Hz, 1 H), 1.50 ppm (s, 9H)
Preparation of r5-r5-(3^,5 richlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl1indan-l-yl1ammonium chloride
Figure imgf000069_0001
To a solution of tert-butyl N-[6-[5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l - yl]carbamate (303 mg) in dichloromethane (2 mL) stirred at 0°C was added hydrogen chloride (2 eq., 4M solution in dioxane). The reaction was stirred at room temperature for 6 days then the reaction was stopped. The precipitate was filtered to give [5-[5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H- isothiazol-3-yl]indan-l -yl]ammonium chloride (163 mg) that was used as such in the next step.
Preparation N-[5-r5-(3.4.5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yllindan-l - yllcyclopropanecarboxamide (Bl)
Figure imgf000069_0002
To a stirred solution of [5-[5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l- yljammonium chloride (80 mg) in dichloromethane (2.5 mL) was added triethylamine (2 eq) at ambient temperature. To this solution was added cyclopropanecarboxylic acid (0.84 eq.), 1- hydroxyazabenzotriazole (1.1 eq.) then l-ethyl-3-(3-dimethylaminopropyl) carbodiimide (1.1 eq). The solution was stirred for 15 hours at ambient temperature. The solution was concentrated under vacuo and „
- 69 - then the crude residue was dissolved in ethyl acetate and treated by a solution of sodium hydroxide (1M). The solution was extracted twice from a solution of sodium hydroxide (1M) and the combined organic phases were combined and dried over anhydrous. The crude residue was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate) to give N-[5-[5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)- 4H-isothiazol-3-yl]indan-l -yl]cyclopropanecarboxamide (76 mg)
lH NMR (CDCl3,400MHz): δ = 7.66 (d, J=9.5 Hz, 1 H), 7.60 (t, J=8.4 Hz, 1 H), 7.46 (s, 2 H), 7.37 (d, J=8.1 Hz, 1 H), 5.78 (d, J=8.4 Hz, 1 H), 5.56 (q, J=7.8 Hz, 1 H), 4.22 (dd, J=17.6, 1.8 Hz, 1 H), 3.86 (d, J=17.6 Hz, 1 H), 2.97 - 3.08 (m, 1 H), 2.85 - 2.97 (m, 1 H), 2.60 - 2.70 (m, 1 H), 1.86 (dq, J=13.0, 8.3 Hz, 1 H), 1.32 - 1.41 (m, 1 H), 1.01 - 1.11 (m, 2 H), 0.75 - 0.85 ppm (m, 2 H)
Similarly, N-[5 - [5 -(3 ,4,5 -trichlorophenyl)-5 -(trifluoromethyl)-4H-isothiazol-3 -yljindan- 1 -yl]propanamide (B2) was prepared: lH NMR (CDCl3,400MHz): δ = 7.66 (d, J=9.9 Hz, 1 H), 7.56 - 7.63 (m, 1 H), 7.46 (s, 2 H), 7.34 (d, J=7.7 Hz, 1 H), 5.47 - 5.66 (m, 2 H), 4.21 (dd, J=17.6, 1.8 Hz, 1 H), 3.86 (d, J=16.5 Hz, 1 H), 3.00 (m, 1 H), 2.81 - 2.96 (m, 1 H), 2.60 - 2.73 (m, 1 H), 2.29 (q, J=7.6 Hz, 2 H), 1.83 (dd, J=12.8, 7.7 Hz 1 H), 1.16 - 1.27 ppm (m, 3 H)
Figure imgf000070_0001
Preparation of N-fS-rfSS^-S-fS^.S-trichlorophenyn-S-ftrifluoromethyn^H-isothiazol-S-yllindan-l - llcyclopropanecarboxamide fB3
Figure imgf000070_0002
Step A: tert-butyl N-[5-[(3S)-3-benzylsulfanyl-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)butanoyl]indan-l- yl]carbamate
Figure imgf000071_0001
To a solution of tert-butyl N-[5-[4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl]indan-l- yl]carbamate (30 g) in tetrahydrofuran (224 ml) was added at -40 C the catalyst 1 -[3,5- bis(trifluoromethyl)phenyl]-3-[(l S,2S)-(+)-2-(dimethylamino)cyclohexylthiourea (232 mg) then under argon atmosphere phenymethanethiol (9.98 ml) was added to the solution cooled at -40°C. The reaction mixture was stirred at -40°C for 17 hours, then more catalyst was added (232 mg). After 4 hours, more catalyst was added (232 mg) and the temperature was increased to -30°C. After another 2 hours, more catalyst was added (116 mg). The reaction mixture was stirred at -30°C for 18 hours, then more catalyst was added (116 mg) and more phenymethanethiol (1.66 ml) was added to the solution. The reaction mixture was then stirred at -20°C for 4 days. Then the temperature was raised to room temperature and after 2 hours, the reaction mixture was quenched with addition of brine then the mixture was extracted with ethyl acetate. The organic layers were combined and dried over sodium sulphate, then concentrated under reduced pressure to give a yellow oil. The crude residue was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate) to give tert-butyl N-[5-[(3S)-3-benzylsulfanyl-4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)butanoyl]indan-l -yl]carbamate (35g). The compound was pure enough to be used in the next step. StepB : tert-butyl N-[5-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l - yl]carbamate (B4)
Figure imgf000071_0002
A solution of tert-butyl N-[5-[(3S)-3-benzylsulfanyl-4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)butanoyl]indan-l-yl]carbamate (18 g) in dichloromethane (100 ml) under argon atmosphere and at -10°C to-5°C was treated with sulfuryl chloride (3 ml) dropwise then the mixture was stirred at -10°C to -5°C for 2 hour. The reaction mixture was then concentrated, the residue was dissolved in tetrahydrofuran (100 ml) under argon and cooled to -10°C. A solution of ammonia (19.5 mL, 7M in methanol) was added dropwise at -10°C to-5°C in 30 min. The mixture was stirred at -10°C until consumption of the reaction intermediate. The reaction mixture was quenched with a addition of 2M aqueous hydrochloric acid solution to acidic pH then stored at 0°C for 16 hours. The mixture was then diluted with ethyl acetate and was extracted with ethyl aceate then the organic phase was washed with water, brine then dried over sodium sulphate and concentrated in vacuo to give a residue, which was purified by chromatography on column (cyclohexane/EtOAc as solvent) to afford the desired product (11.2 g).
Preparation of N-[5-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l- yl cyclopropanecarboxamide (B3)
Figure imgf000072_0001
After a deprotection step and an acylation step, similarly to the preparation of compound Bl, the enriched N-[5-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l- yl]cyclopropanecarboxamide could be prepared starting from : tert-butyl N-[5-[(5S)-5-(3,4,5- trichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l-yl]carbamate.
Chiral HPLC analysis using a Waters UPLC - Hclass, DAD Detector Waters UPLC._Column: Daicel CHIRALPAK® IA, 3μιη, 0.46cm x 1 OcmJVIobile phase: TBME/EtOH 98/02^Flow rate: 1.0 ml/min^ Detection: 313._Sample concentration: lmg/mL in Hept/iPrOH 50/50._Injection: 2μΙ^. Peak 1 : 3.02 min; 47.7 %; Peak 2: 3.57 min; 0.8%; Peak 2: 5.92 min; 0.8%; Peak 2: 8.13 min; 49.8%
Method for preparing compounds of the invention from an amine
Figure imgf000072_0002
To a solution of 5-[(5S)-5-(3,4,5 richlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]indan-l -amine as a TFA salt (0.16 mmol) with diisopropylethylamine (6.3 eq) in DCM/DMF 4: 1 (0.5 ml) was added successively an acid or an acyl chloride (3.1 eq) and a solution of N,N,N',N'-tetramethyl-o-(benzotriazol- l-yl)uranium tetrafluoroborate (1.9 eq) in DCM/DMF 4: 1 (0.5 ml). The reaction mixture was stired at room temperature for 3 hours. After LC-MS analysis, the solvent was dried and the crude was dissolved in DMF to be purified by preparative HPLC. This method was used to prepare compounds B5 to B53 in parallel, indicated in Table A below
LC/MS Method A
MS ACQUITY SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer)
Ionisation method: Electrospray
Polarity: positive ions
Capillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature (°C) 150,
Desolvation Temperature (°C) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700
Mass range: 100 to 800 Da
DAD Wavelength range (nm): 210 to 400
LC Method Waters ACQUITY UPLC with the following HPLC gradient conditions
(Solvent A: Water/Methanol 9:1,0.1% formic acid and Solvent B: Acetonitrile,0.1 % formic acid )
Time (minutes) A (%) B (%) Flow rate (ml/min)
0 100 0 0.75
2.5 0 100 0.75
2.8 0 100 0.75
3.0 100 0 0.75
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60°C.
Table A
The experimental data was obtained using LC/MS method A
Comp No. R Retention time (Min) (M+H) + (measured)
B5 vinyl 2.21 519.17
B6 fluoromethyl 2.2 525.1
B7 prop-l -enyl 2.28 532.52
B8 isopropyl 2.1 535.42
B9 propyl 2.3 535.11
B10 methoxymethyl 2.21 537.15
Bl l cyclobutyl 2.56 547.25
B12 but-2-yl 2.38 549.12
B13 tert-butyl 2.4 548.6
B14 2-methylprop- 1 -yl 2.38 549.42 B15 cyclopentyl 2.38 560.62
B16 pent-3-yl 2.42 563.06
B17 2-methylsulfanylethyl 2.29 566.89
B18 pyridin-2-yl 2.41 570.48
B19 5-methylisoxazol-3 -yl 2.34 574.06
B20 thiophen-2-yl 2.33 575.07
B21 cyclohexyl 2.87 575.31
B22 cyclopentylmethyl 2.47 575.33
B23 benzyl 2.33 583.18
B24 2-thienylmethyl 2.37 589.2
B25 phenoxymethyl 2.48 599.04
B26 2-chloropyridin-4-yl 2.35 603.9
B27 6-chloropyridin-3 -yl 2.33 603.78
B28 3 -fluorophenyl 2.38 587.45
B29 2-methoxyphenyl 2.5 599.29
B30 4-fluoro-2-methyl-phenyl 2.39 600.59
B31 4-cyano-2-methyl-phenyl 2.35 608.06
B32 cyanomethyl 2.13 531.52
B33 2-methylcyclopropyl 2.31 547.15
B34 cyclopropylmethyl 2.31 547.4
B35 1 -hydroxycyclopropyl 2.13 549.48
B36 2-fluorocyclopropyl 2.2 551.29
B37 1 -methoxy ethyl 2.27 551.49
B38 cyclopent-3 -en- 1 -yl 2.33 558.88
B39 tetrahydrofuran-2-yl 2.28 563
B40 tetrahydrofuran-3 -yl 2.16 563.15
B41 2-acetoxyethyl 2.16 565.37
B42 isopropoxymethyl 2.39 564.86
B43 cyclohex-3-en-l -yl 2.41 573.14
B44 2,2,2-trifluoroethyl 2.31 575.17
B45 tetrazol- 1 -ylmethyl 2.07 575.33
B46 2-pyridylmethyl 2.02 583.83
B47 methylsulfonylmethyl 2.12 585.13
B48 1 -phenylcyclopropyl 2.51 609.13
B49 furan-2-yl 2.27 559.27 B50 pyridin-4-yl 2.15 569.61
B51 (4 -chlorophenyl)methyl 2.43 617.17
B52 cyclopropyl 2.24 533.11
B53 methyl 2.12 507.09
Biological examples of racemic mixtures
Spodoptera Uttoralis (Egyptian cotton leafworm):
Cotton leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with 5 LI larvae. The samples were checked for mortality, feeding behavior, and growth regulation 3 days after treatment (DAT).
The following compound gave at least 80% control of Spodoptera Uttoralis: Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B18, B19, B20, B21 , B22, B23, B24, B25, B26, B27 B29, B30, B31, B32, B33, B34, B35, B36, B37, B38, B39, B40, B41 , B42, B43, B44, B45, B46, B47, B49, B50, B52, B53.
Heliothis virescens (Tobacco budworm):
Eggs (0-24 h old) were placed in 24-well microtiter plate on artificial diet and treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After an incubation period of 4 days, samples were checked for egg mortality, larval mortality, and growth regulation.
The following compound gave at least 80%> control of Heliothis virescens: Bl, B2, B3, B5, B6, B7, B8, B9, B10, Bl l, B12, B13, B14, B15, B16, B17, B18, B19, B20, B21, B22, B23, B24, B25, B26, B27, B28, B29, B30, B31 , B32, B33, B34, B35, B36, B37, B38, B39, B40, B41, B42, B43, B44, B45, B46, B47, B48, B49, B50, B51, B52, B53.
Plutella xylostella (Diamond back moth):
24-well microtiter plate (MTP) with artificial diet was treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After drying, the MTPs were infested with L2 larvae (7-12 per well). After an incubation period of 6 days, samples were checked for larval mortality and growth regulation.
The following compound gave at least 80%> control of Plutella xylostella: Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B18, B19, B20, B21 , B22, B23, B24, B25, B26, B27, B28, B30, B31, B32, B33, B34, B35, B36, B37, B38, B39, B40, B41 , B42, B43, B44, B45, B46, B47, B49, B50, B51, B52, B53.
Diabrotica balteata (Corn root worm):
A 24-well microtiter plate (MTP) with artificial diet was treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After drying, the MTPs were infested with L2 larvae (6-10 per well). After an incubation period of 5 days, samples were checked for larval mortality and growth regulation.
The following compound gave at least 80% control of Diabrotica balteata: Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B18, B19, B20, B21 , B22, B23, B24, B25, B26, B27, B28, B29, B30, B31 , B32, B33, B34, B35, B36, B37, B38, B39, B40, B41, B42, B43, B44, B45, B46, B47, B49, B50, B51 , B52, B53.
Thrips tabaci (Onion thrips):
Sunflower leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with a thrips population of mixed ages. After an incubation period of 7 days, samples were checked for mortality.
The following compounds gave at least 80% control of Thrips tabaci: Bl, B2, B3, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B19, B20, B21 , B22, B23, B24, B25, B27, B29, B30, B31 , B32, B33, B34, B35, B36, B37, B38, B39, B40, B41, B42, B43, B44, B45, B46, B47, B49, B50, B52, B53.
Tetranychus urticae (Two-spotted spider mite):
Bean leaf discs on agar in 24-well microtiter plates were sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs are infested with mite populations of mixed ages. 8 days later, discs are checked for egg mortality, larval mortality, and adult mortality.
The following compound gave at least 80%> control of Tetranychus urticae: Bl, B2, B3, B4, B5, B6, B7, B8, B9, B10, Bl l , B12, B13, B14, B15, B16, B17, B19, B20, B21, B22, B23, B24, B25, B26, B27, B28, B30, B31 , B32, B33, B34, B35, B36, B37, B38, B39, B40, B41, B42, B43, B44, B45, B46, B47, B49, B50, B51 , B52, B53.
Biological Examples - safety profile
Spodoptera littoralis (Egyptian cotton leafworm)
Cotton plants in the 5th leaf stage (around 5 weeks old) are treated in an automated turn table spray chamber with compounds of the invention at a desired rate of application. Plants are stored in the greenhouse length during the whole test period. 2,16 and optionally 10 days after treatment 4 leaves from each sample are excised, placed into 14cm plastic petri dishes on wet filter paper. The infestation of 10 L3-Spodoptera littoralis is made immediately afterwards. After an incubation period of 6 days the samples are checked for mortality. It has been found that compounds containing an isothiazoline ring are highly potent 2 days after application but lose significant activity 16 days after application. On the other hand, compounds containing an isoxazoline ring lose little activity 16 days after application. This suggests that compounds „ ,
- 76 - containing an isothiazoline ring are more degradable than compounds containing an isoxazoline ring, such as those described in EP 1,731,512.

Claims

1. A compound of formula (I)
Figure imgf000078_0001
wherein
A1, A2, and A3 are independently of each other C-H, C-R7, or nitrogen;
X1 represents a two- to four-membered bridge containing carbon atoms as bridge members, optionally containing one or more double bonds, and each bridge member is optionally substituted by one or two R6;
R1 is Ci-Cghaloalkyl;
R2 is aryl or aryl substituted by one to five R11, or heteroaryl or heteroaryl substituted by one to five R11;
R3 is hydrogen,
Figure imgf000078_0002
substituted by one to five R8, C3-Cgcycloalkyl or C3- Cgcycloalkyl substituted by one to five R9, C2-Ci2alkenyl or C2-Ci2alkenyl substituted by one to five R8, C2-Ci2alkynyl or C2-Ci2alkynyl substituted by one to five R8, cyano,
Figure imgf000078_0003
or Ci_
Ci2alkoxycarbonyl substituted by one to five R8,
Figure imgf000078_0004
substituted by one to five R8;
R4 is hydrogen, NH2, hydroxyl, C1-C12 alkoxy or Ci-Ci2alkoxy substituted by one to five R8, Q- Ci2alkylcarbonylamino or
Figure imgf000078_0005
wherein the alkyl is substituted by one to five R8, Ci-Ci2alkylamino or
Figure imgf000078_0006
or Ci-Ci2alkyl substituted by one to five R8, C3-Cgcycloalkyl or C3-Cgcycloalkyl substituted by one to five R9, cyano, C2-Ci2alkenyl or C2-Ci2alkenyl substituted by one to five R8, C2-Ci2alkynyl or C2-Ci2alkynyl substituted by one to five R8, Q-C^alkylcarbonyl or Q-C^alkylcarbonyl substituted by one to five R8, Ci-Ci2alkoxycarbonyl or
Figure imgf000078_0007
substituted by one to five R8 or is selected from CH2-R13, C(=0)R13 and C(=S)R13;
R5 is hydrogen, cyano, carbonyl, thiocarbonyl,
Figure imgf000078_0008
or C1-C12 alkylcarbonyl substituted by one to five R8,
Figure imgf000078_0009
or Ci-Cnalkylthiocarbonyl substituted by one to five R8, Ci-Ci2alkylaminocarbonyl or Ci-Cnalkylaminocarbonyl wherein the alkyl is substituted by one to five R8, Ci-Ci2alkylaminothiocarbonyl or
Figure imgf000078_0010
wherein the alkyl is substituted by one to five R8, C2-C24 (total carbon number) dialkylaminocarbonyl or C2-C24 (total carbon - /o - number) dialkylaminocarbonyl wherein one or both alkyl is substituted by one to five R8, C2-C24 (total carbon number) dialkylaminothiocarbonyl or C2-C24 (total carbon number) dialkylaminothiocarbonyl wherein one or both alkyl is substituted by one to five R8,
Figure imgf000079_0001
or d- Ci2alkoxyaminocarbonyl wherein the alkoxy is substituted by one to five R8, Cp
Ci2alkoxyaminothiocarbonyl or
Figure imgf000079_0002
wherein the alkoxy is substituted by one to five R8,
Figure imgf000079_0003
substituted by one to five R8, d- Ci2alkoxythiocarbonyl or
Figure imgf000079_0004
substituted by one to five R8, Cp
Ci2thioalkoxycarbonyl or Ci-Ci2thioalkoxycarbonyl substituted by one to five R8, Cp
Ci2thioalkoxythiocarbonyl or Ci-Cnthioalkoxythiocarbonyl substituted by one to five R8, d- Ci2alkylsulfonyl or
Figure imgf000079_0005
substituted by one to five R8, C3-Ci2cycloalkylcarbonyl or C3- Ci2cycloalkylcarbonyl substituted by one to five R9, C2-Ci2alkenylcarbonyl or C2-Ci2alkenylcarbonyl substituted by one to five R8, C2-Ci2alkynylcarbonyl or C2-Ci2alkynylcarbonyl substituted by one to five R8, C3-Ci2cycloalkyl-Ci-Ci2alkylcarbonyl or C3-Ci2cycloalkyl-Ci-Ci2alkylcarbonyl substituted by one to five R9, Ci-Ci2alkylsulfenyl-Ci-Ci2alkylcarbonyl or Ci-C^alkylsulfenyl-Ci-C^alkylcarbonyl substituted by one to five R8, Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl or Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl substituted by one to five R8, C1-C12
Figure imgf000079_0006
Ci2alkylcarbonyl substituted by one to five R8, Ci-C^alkylcarbonyl-Ci-C^alkylcarbonyl or Cr
Ci2alkylcarbonyl-Ci-Ci2alkylcarbonyl substituted by one to five R8, C3-Ci2cycloalkylaminocarbonyl or C3-Ci2cycloalkylaminocarbonyl wherein the cycloalkyl is substituted by one to five R9, C2- Ci2alkenylaminocarbonyl or C2-Ci2alkenylaminocarbonyl wherein the alkenyl is substituted by one to five R8, C2-Ci2alkynylaminocarbonyl or C2-Ci2alkynylaminocarbonyl wherein the alkynyl is substituted by one to five R8, or is selected from C(=0)R13 and C(=S)R13,
or R4 and R5 together with the nitrogen atom to which they are bound, form a 3- to 6-membered heterocyclic ring which may be substituted by one to five R14, or may be substituted with a keto, thioketo or nitroimino group;
each R6 is independently hydrogen, halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, C2- C8alkenyl, C2-C8haloalkenyl, C2-C8alkynyl, C2-C8haloalkynyl, hydroxy, CpCgalkoxy, CpCghaloalkoxy, mercapto, Ci-C8alkylthio, Ci-Cghaloalkylthio, CpCgalkylsulfinyl, CpCghaloalkylsulfinyl, Cr
Cgalkylsulfonyl, Ci-Cghaloalkylsulfonyl, CpCgalkylcarbonyl, CpCgalkoxycarbonyl, aryl or aryl substituted by one to five R12, or heterocyclyl or heterocyclyl substituted by one to five R12;
each R7 is independently halogen, cyano, nitro, CpCgalkyl, C3-Cgcycloalkyl, Ci-Cghaloalkyl, - Cgalkenyl, C2-Cghaloalkenyl, C2-Cgalkynyl, C2-Cghaloalkynyl, d-Cgalkoxy, CpCghaloalkoxy, Cp Cgalkoxycarbonyl-, or two R7 on adjacent carbon atoms together form a -CH=CH-CH=CH- bridge or a - N=CH-CH=CH- bridge;
each R8 is independently halogen, cyano, nitro, hydroxy, NH2, mercapto, CpCgalkyl, Q- Cghaloalkyl, C3-Cgcycloalkyl, d-Cgalkoxy, CpCghaloalkoxy, Ci-Cgalkylthio, Ci-Cghaloalkylthio, Cp Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, Ci-Cgalkylsulfonyl, Ci-Cghaloalkylsulfonyl, Ci-Cgalkylamino, C2-Cgdialkylamino, C3-Cgcycloalkylamino, CpCgalkylcarbonyl, CpCgalkoxycarbonyl, Cr Cgalkylammocarbonyl, Ci-Cgdialkylaminocarbonyl, Ci-Cghaloalkylcarbonyl, Ci-Cghaloalkoxycarbonyl, Ci -Cghaloalkylaminocarbonyl, C i -Cghalodialkylaminocarbonyl;
each R9 is independently halogen, cyano or d-Cgalkyl;
each R10 is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, C2-Cgalkenyl, C2- Cghaloalkenyl, C2-Cgalkynyl, C2-Cghaloalkynyl, hydroxy, Q-Cgalkoxy, Ci-Cghaloalkoxy, mercapto, Cp Cgalkylthio, CpCghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, CpCgalkylsulfonyl, d- Cghaloalkylsulfonyl, d-Cgalkylcarbonyl, Ci-Cgalkoxycarbonyl, aryl or aryl substituted by one to five R12 or heterocyclyl or heterocyclyl substituted by one to five R12;
each R11 is independently hydrogen, halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, C2- Cgalkenyl, C2-Cghaloalkenyl, C2-Cgalkynyl, C2-Cghaloalkynyl, hydroxy, Ci-Cgalkoxy, Ci-Cghaloalkoxy, mercapto, Ci-C8alkylthio, Ci-Cghaloalkylthio, Ci-Cgalkylsulfinyl, Ci-Cghaloalkylsulfinyl, Cr
Cgalkylsulfonyl, CpCghaloalkylsulfonyl, CpCgalkylcarbonyl, CpCgalkoxycarbonyl, aryl or aryl substituted by one to five R12, or heterocyclyl or heterocyclyl substituted by one to five R12;
each R12 is independently halogen, cyano, nitro, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy-, or Cr C4haloalkoxy-;
R is aryl or aryl substituted by one to five R , heterocyclyl or heterocyclyl substituted by one to five R 10.
each R is independently halogen, cyano, nitro, CpCgalkyl, Ci-Cghaloalkyl, Q-Cgalkoxy, Cr
Cghaloalkoxy or Q-Cgalkoxycarbonyl;
or a salt or N-oxide thereof.
2. A compound according to claim 1 wherein A1, A2 and A3 are independently C-H or nitrogen, wherein no more than two of A1, A2 and A3 are nitrogen, and A2 and A3 are not both nitrogen.
3. A compound according to claim 1 or claim 2, wherein R1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl.
4. A compound according to any one of claims 1 to 3, wherein R2 is group P
Figure imgf000080_0001
wherein X is N or C-R11.
5. A compound according to any one of claims 1 to 4, wherein R is hydrogen, halogen, cyano, Cr Qalkyl, Ci-C haloalkyl or C3-C6 cycloalkyl.
6. A compound according to any one of claims 1 to 5, wherein R is hydrogen, Ci-Cgalkyl, d- Cghaloalkyl, d-Cgalkoxy, Ci-Cghaloalkoxy, Ci-Cgalkylcarbonyl, CpCghaloalkylcarbonyl, d- Cgalkoxycarbonyl, or Ci-Cghaloalkoxycarbonyl.
7. A compound according to any one of claims 1 to 6, wherein R5 is hydrogen, cyano, carbonyl, thiocarbonyl, Ci-Cgalkylcarbonyl, Ci-Cnhaloalkylca d-
Figure imgf000081_0001
Ci-Ci2haloalkylaminocarbonyl, Ci-C^haloalkylaminothiocarbonyl, C2-C24 (total carbon number) dialkylaminocarbonyl, C2-C24 (total carbon number) dialkylaminothiocarbonyl, d- Ci2alkoxyaminocarbonyl,
Figure imgf000081_0002
Ci- Cghaloalkoxycarbonyl, Ci-Ci2alkoxythiocarbonyl,
Figure imgf000081_0003
Cp
Ci2thioalkoxycarbonyl,
Figure imgf000081_0004
C3- Ci2cycloalkylcarbonyl, C3-Ci2halocycloalkylcarbonyl, C2-Ci2alkenylcarbonyl, C2- Ci2haloalkenylcarbonyl, C2-Ci2 alkynylcarbonyl, C2-Ci2haloalkynylcarbonyl, C3-Ci2cycloalkyl-Ci- Ci2alkylcarbonyl, d-C^halocycloalkyl-Ci-Cnalkylcarbonyl, C2-Ci2alkylsulfenyl-Ci-Ci2alkylcarbonyl, Ci-Ci2haloalkylsulfenyl-Ci-Ci2alkylcarbonyl, Ci-C^alkylsulfinyl-Ci-C^alkylcarbonyl, Cr
Ci2haloalkylsulfinyl-C 1 -C i2alkylcarbonyl,
Figure imgf000081_0005
C 1 - Ci2haloalkylsulfonyl-Ci-Ci2alkylcarbonyl, Ci-C^alkylcarbonyl-Ci-Cnalkylcarbonyl, Q- Ci2haloalkylcarbonyl-Ci-Ci2alkylcarbonyl, C3-Ci2cycloalkylaminocarbonyl, - Ci2alkenylaminocarbonyl, C2-Ci2alkynylaminocarbonyl or C(=0)R13.
8. A compound according to any one of claims 1 to 6, wherein R5 is CpCgalkylcarbonyl, Cr Cghaloalkylcarbonyl, Ci-Ci2alkoxycarbonyl, C3-Cgcycloalkylcarbonyl, C3-Cghalocycloalkylcarbonyl, C3- Cgcycloalkyl-CH2-carbonyl, C3-Cghalocycloalkyl-CH2-carbonyl, Ci-Cgalkylsulfenyl-CH2-carbonyl, Cr Cghaloalkylsulfenyl-CH2-carbonyl, Ci-Cgalkylsulfinyl-CH2-carbonyl, Ci-Cghaloalkylsulfinyl-CH2- carbonyl, Ci-Cgalkylsulfonyl-CH2-carbonyl, or Ci-Cghaloalkylsulfonyl-CH2-carbonyl, Cr
Cgalkylaminocarbonyl, C3-Cgcycloalkylaminocarbonyl, or C(=0)R13 wherein R13 is phenyl or phenyl substituted by one to five R14, or pyridyl or pyridyl substituted by one to five R14.
9. A compound according to any one of claims 1 to 8, wherein X1 represents
-C(R6)(R6)-C(R6)(R6)- or -C(R6)(R6)-C(R6)(R6)-C(R6)(R6)-.
10. A compound according to claim 1 wherein
A1 is C-H, or nitrogen, A2 and A3 are independently C-H or nitrogen, wherein no more than two of A1, A2 and A3 are nitrogen, and A2 and A3 are not both nitrogen;
X1 represents -CH2-CH2- or -CH2-CH2-CH2-;
R1 is chlorodifluoromethyl, difluoromethyl or trifluoromethyl; R2 is group P
Figure imgf000082_0001
wherein X2 is N or C-R11;
R3 is hydrogen, methyl, ethyl or cyclopropyl;
R4 is hydrogen, Ci-C4alkyl or CrQhaloalkyl;
R5 is C(=0)-R15;
each R11 is independently hydrogen, bromo, chloro or trifluoromethyl providing that at least two R11 are not hydrogen;
R15 is CrC4alkyl, C C4haloalkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-Ci-C4alkyl,
C3.C6halocycloalkyl, Ci-C4alkoxy, Ci-C4alkoxy-Ci-C4alkyl, Ci-C4haloalkoxy-Ci-C4alkyl, C1-C4 alkylthio-Ci-C4alkyl, Ci-C4alkylsulfinyl-Ci-C4alkyl, Ci-C4alkylsulfonyl-Ci-C4alkyl, Ci-C4alkylamino, d- C4haloalkylamino, Cs-Cgcycloalkylamino, phenyl optionally substituted by halogen or pyridylmethyl.
11. A compound of formula Int-1
Figure imgf000082_0002
(Int-1)
1 2 3 1 1 2 3
wherein A , A , A X1, R , R", and RJ are as defined for cmopounds of fomula I as defined in any one of claims 1 to 10, or a salt of N-oxide thereof, or
a compound of formula Int-2
Figure imgf000083_0001
1 2 3 1 1 2 3 4 5
wherein A , A , A X1, R , R", R\ R and RJ are as defined for compounds of fomula I in any one of claims 1 to 10, and R is H, cyano, halogen, CpCgalkyl, Ci-C8alkylcarbonyl, arylsulfinyl wherein the aryl is optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy and Ci-C4haloalkoxy, arylsulfonyl wherein the aryl is optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Cr Qalkoxy and CrQhaloalkoxy, benzyl optionally substituted by one to five groups independently selected from halogen, cyano, Ci-C alkyl, Ci-C haloalkyl, Ci-C alkoxy and Ci-C haloalkoxy, or a salt of N-oxide thereof.
12. A method of controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 10.
13. An insecticidal, acaricidal, nematicidal or molluscicidal composition comprising an
insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 10.
14. An insecticidal, acaricidal, nematicidal or molluscicidal composition according to claim 13 comprising at least one additional compound having biological activity.
15. 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 formula (I) as defined in any one of claims 1 to 10, and compound 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, - oj - 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.
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WO2014206908A1 (en) * 2013-06-24 2014-12-31 Basf Se Isothiazoline compounds substituted with a carbobicyclic group
CN105473563A (en) * 2013-06-24 2016-04-06 梅里亚股份有限公司 Isothiazoline compounds substituted with a carbobicyclic group
US9420793B2 (en) 2015-01-16 2016-08-23 Avista Pharma Solutions Antiparasitic compounds
US9686991B2 (en) 2015-01-16 2017-06-27 Avista Pharma Solutions, Inc. Antiparasitic compounds
US9883674B2 (en) 2015-01-16 2018-02-06 Avista Pharma Solutions, Inc. Antiparasitic compounds
JP2018509463A (en) * 2015-01-16 2018-04-05 アビスタ ファーマ ソリューションズ，インコーポレーテッド Antiparasitic compounds
US10092001B2 (en) 2015-01-16 2018-10-09 Avista Pharma Solutions, Inc. Antiparasitic compounds
US10342234B2 (en) 2015-01-16 2019-07-09 Avista Pharma Solutions, Inc. Antiparasitic compounds
JP2020117505A (en) * 2015-01-16 2020-08-06 アビスタ ファーマ ソリューションズ，インコーポレーテッド Antiparasitic compounds
US10772331B2 (en) 2015-01-16 2020-09-15 Avista Pharma Solutions, Inc. Antiparasitic compounds
US10807992B2 (en) 2017-11-16 2020-10-20 Avista Pharma Solutions, Inc. Single enantiomer antiparasitic compounds
CN110845436A (en) * 2019-11-18 2020-02-28 合肥锦绣田园化工科技有限公司 Thiazolesulfone compound and preparation and application thereof

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