WO2012069601A1 - Substituted quinazolines as fungicides - Google Patents

Substituted quinazolines as fungicides Download PDF

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WO2012069601A1
WO2012069601A1 PCT/EP2011/070966 EP2011070966W WO2012069601A1 WO 2012069601 A1 WO2012069601 A1 WO 2012069601A1 EP 2011070966 W EP2011070966 W EP 2011070966W WO 2012069601 A1 WO2012069601 A1 WO 2012069601A1
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Clemens Lamberth
Laura Quaranta
Andrew Edmunds
Martin Pouliot
Stephan Trah
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Syngenta Participations Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—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
    • A01N43/74—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 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • 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
    • A01N43/74—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 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • 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
    • A01N43/82—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 three ring hetero atoms
    • 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
    • A01N43/88—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 six-membered rings with three ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero 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

Definitions

  • the present invention relates to novel quinazoline containing compounds, their use in compositions and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
  • Fungicides are compounds, of natural or synthetic origin, which act to protect plants against damage caused by fungi.
  • Current methods of agriculture rely heavily on the use of fungicides. In fact, some crops cannot be grown usefully without the use of fungicides.
  • Using fungicides allows a grower to increase the yield of the crop and consequently, increase the value of the crop. Numerous fungicidal agents have been developed. However, the treatment of fungal infestations continues to be a major problem. Furthermore, fungicide resistance has become a serious problem, rendering these agents ineffective for some agricultural uses. As such, a need exists for the development of new fungicidal compounds.
  • R 1 is hydrogen, halogen, cyano, Ci- 6 alkyl, C 3 - 6 cycloalkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy or Ci- 6 alkylthio;
  • R , R R R , R° and R' are, independently from each other, hydrogen, hydroxy, halogen, Ci- 6 alkyl, C 3 - 6 cycloalkyl or Ci- 6 alkoxy;
  • A is heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio or heteroarylalkynyl; or a salt or a N-oxide thereof.
  • substituents A, R , R , R , R , R and R are unsubstituted or substituted. When the substituents are unsubstituted then they are preferably substituted by the substituents given below, wherein the meaning of the
  • the invention covers all agronomically acceptable salts, isomers, structural isomers, stereoisomers, diastereoisomers, enantiomers, tautomers and N-oxides of those compounds.
  • the compounds of formula I may exist in different geometric or optical isomeric forms or in different tautomeric forms. One or more centres of chirality may be present, in which case compounds of the formula I may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of diastereomers.
  • This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. Also atropisomerism may occur as a result of a restricted rotation abaout a
  • Suitable salts of the compounds of formula I include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid.
  • organic carboxylic acids include haloacids such as trifluoroacetic acid.
  • N-oxides are oxidised forms of tertiary amines or oxidised forms of nitrogen containing heteroaromatic compounds. They are described in many books for example in "Heterocyclic N-oxides" by Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Florida, 1991.
  • alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, ⁇ -propyl, «-butyl, n- pentyl, «-hexyl, z ' so-propyl, «-butyl, sec-butyl, zso-butyl or tert-butyl.
  • Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned.
  • the alkenyl and alkynyl groups can be mono- or di-unsaturated.
  • the cycloalkyl groups are, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine more preferably chlorine or fluorine. This also applies, correspondingly, to halogen in combination with other meanings, such as halogenalkyl or halogenalkoxy.
  • Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms and comprise at least one halogen atom up to perhalogenated alkyle group.
  • Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, l, l-difluoro-2,2,2-trichloroethyl, 2,2,3, 3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy; preferably methoxy and ethoxy.
  • Halogenalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1, 1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2- difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
  • Thioalkyl is, for example, methylthio, ethylthio, propylthio, tert-butylthio, hexylthio.
  • Alkylamino is, for example, methylamino, ethylamino, propylamino, tert-butylamino, hexylamino as well as, for example dimethylamino, diethylamino, dipropylamino, ditert-butylamino, dihexylamino or trimethylamino, triethylamino, tripropylamino, tri tert-butylamino, trihexylamino or 2- to 3-fold substituted amines with different alkyl groups.
  • the preferred substituents of the substituted alkyl groups, the substituted cycloalkyl groups, the substituted alkenyl groups, the substituted alkynyl groups and the substituted alkoxy group in the compound of formula (I) are selected from the following substituents F, CI, Br, I, -OH, -CN, nitro, -Ci- 4 alkoxy, -C 1 -4 alkylthio, -
  • R 17 and R 1 1 8 0 are independently H, -Ci- 4 alkyl or substituted -Ci- 4 alkyl or combine with the interjacent nitrogen to form a five- or six-membered ring which may comprise one or two or three heteroatoms (one or two N, O or S atoms in addition to the interjacent nitrogen atom), in which case the heterocyclic ring is unsubstituted or the heterocyclic ring is substituted by one or two C 1 -4 alkyl groups, - C(0)H, -C(0)(Ci -4 alkyl), -C(0)(Ci -4 alkoxy), -C(0) H 2 , -C(0) H(Ci -4 alkyl), - C(0)N(Ci -4 alkyl)(Ci -4 alkyl), -OC(0) H(Ci -4 alkyl), -OC(0)N(Ci -4 alkyl)(Ci -4 alkyl), -HC(0)(Cii -4 al
  • the more preferred substituents of the substituted alkyl groups are selected from the following substituents -OH, CN, F, CI, Ci- 4 alkoxy, Ci- 4 alkylamino.
  • the alkyl groups are branched or linear.
  • the most preferred alkyl groups are methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl (2-methylpropyl), pentyl, 1-methylpentyl, 1- ethylpentyl, iso-pentyl (3-methylbutyl), hexyl, heptyl, octyl, or nonyl.
  • the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than two further substituents, more preferably the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than one further substituent, most preferred the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) are not further substituted.
  • “Heteroaryl” refers to aromatic ring systems comprising mono-, bi- or tricyclic systems wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member.
  • Heteroaryl may mean substituted or unsubstituted heteroaryl unless otherwise indicated and hence the heteroaryl moieties may be unsubstituted or substituted with one or more of the same or different substituents.
  • Representative examples of heteroaryl include, for example, benzimidazolyl,
  • benzotriazolyl benzoxazolyl, cinnolinyl, dibenzofuranyl, furyl, imidazolyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazinyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazinyl and triazolyl.
  • substituents for "hetreoaryl” groups may be selected from the list including aryl, cycloalkyl, cycloalkenyl and heterocyclic moiety containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure, halogen, alkyl, haloalkyl, cycloalkyl,
  • cycloalkylalkyl alkenyl, haloalkenyl, cycloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, cycloalkyloxy, haloalkenyloxy, haloalkynyloxy, alkylthio, haloalkylthio, alkyl carbonyl, haloalkylcarbonyl, cycloalkylcarbonyl,
  • Preferred substituents are aryl, cycloalkyl, cycloalkenyl and heterocyclic moiety containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure, Ci -4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3- s cycloalkyl, halo, Ci -4 haloalkyl, Ci -4 alkoxy, Ci -4 haloalkoxy, -C(0)(Ci -4 alkoxy), - C(0)(Ci -4 alkyl), -C(0)H, Ci -4 alkylthio, Ci -4 haloalkylthio nitro and cyano and are more preferably halogen (in particular, fluoro or chloro), cyano, alkyl (in particular, methyl and ethyl), haloalkyl (in particular, trifluoromethyl), alkoxy (in particular, methoxy or
  • Heteroarylalkyl means a radical -R a R b where R a is an alkylene group and R b is an unsubstituted or substituted heteroaryl group as defined above;
  • Heteroarylalkynyl means a radical -R a R b where R a is an alkynylene group as defined below and R b is an unsubstituted or substituted heteroaryl group as defined above.
  • Heteroaryloxy means a radical -OR, wherein R is an heteroaryl group as defined above.
  • Heteroarylthio means a radical -SR, where R is an heteroaryl group as defined above
  • the groups defined above when used alone or as part of a compound term may be unsubstituted or substituted by one or more substituents.
  • alkyl, alkoxy, haloalkyl, haloalkoxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio and heteroarylalkynyl groups may be unsubstituted or substituted.
  • these optional substituents are independently selected from halogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, haloalkenyl, cycloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, cycloalkyloxy, haloalkenyloxy, haloalkynyloxy, alkylthio, haloalkylthio,
  • cycloalkylthio alkyl carbonyl, haloalkylcarbonyl, cycloalkylcarbonyl,
  • Preferred substituents are alkyl, alkenyl, alkynyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy and cyano and are more preferably halogen (in particular, fluoro or chloro), cyano, alkyl (in particular, methyl and ethyl), haloalkyl (in particular, trifluoromethyl), alkoxy (in particular, methoxy or ethoxy),haloalkoxy, aryl, cycloalkyl, cycloalkenyl and heterocyclic moiety containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure.
  • the compounds of formula I may exist in different geometric or optical isomeric forms or in different tautomeric forms. One or more centres of chirality may be present, in which case compounds of the formula I may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of
  • Suitable salts of the compounds of formula I include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid.
  • organic carboxylic acids include haloacids such as trifluoroacetic acid.
  • the preferred alkyl groups and the preferred alkoxy groups are methyl, ethyl, propyl, methoxy and ethoxy groups. Methyl, ethyl and methoxy groups are very particularly preferred.
  • R 1 is hydrogen, halogen, cyano, Ci- 6 alkyl, C3- 6 cycloalkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy or Ci- 6 haloalkoxy; more preferably R 1 is hydrogen, halogen, Ci- 6 alkyl, Ci_ 6 haloalkyl, Ci- 6 alkoxy or Ci- 6 haloalkoxy; even more preferably R 1 is hydrogen, halogen, Ci- 6 alkyl, Ci- 6 haloalkyl or Ci- 6 alkoxy; most preferabley R 1 is hydrogen, halogen, Ci- 6 alkyl or Ci- 6 alkoxy;
  • R , R R R , R° and R' are, independently from each other, hydrogen, halogen, Ci_
  • R , R , R , R and R are, independently from each other, hydrogen, halogen or Ci- 6 alkoxy;
  • A is heteroaryl, heteroarylalkyl, heteroarylthio or heteroalkynyl, more preferably A is heteroaryl, heteroarylalkyl or heteroarylthio, even more preferably A is heteroaryl or heteroarylalkyl.
  • Most preferred optionally substituted heteroaryl moiety in the subtituents A are furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrazolyl, pyridyl, quinolinyl, pynmidinyl, benzooxazolyl, benzothiazolyl, indazolyl, benzo[l,2,5]oxadiazolyl, benzo[l,2,5]thiadiazolyl, or dibenzofuranyl and especially preferred optionally substituted substituents A are furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrazolyl, pyridyl, quinolinyl, pyrimidinyl, benzooxazolyl, benzothiazolyl, indazolyl, benzo[l,2,5]oxadiazolyl, benzo[l,2,5]thiadiazolyl, or dibenzofuranyl
  • Preferred compounds of formula I according to the invention are those wherein R 1 is hydrogen, halogen, cyano, Ci- 6 alkyl, C 3 - 6 cycloalkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy or Ci- 6 haloalkoxy;
  • R , R R R , R° and R' are, independently from each other, hydrogen, halogen, Ci_ 6 alkyl, C 3 - 6 cycloalkyl or Ci- 6 alkoxy;
  • A is heteroaryl, heteroarylalkyl, heteroarylthio or heteroalkynyl.
  • More preferred compounds of formula I according to the invention are those wherein R 1 is hydrogen, halogen, cyano, Ci- 6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy or Ci_
  • R , R , R , R , R and R are, independently from each other, hydrogen, halogen, Ci_ 6 alkyl or Ci- 6 alkoxy;
  • A is heteroaryl, heteroarylalkyl, heteroarylthio or heteroalkynyl. Even more preferred compounds of formula I according to the invention are those wherein
  • R 1 is hydrogen, halogen, Ci- 6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy or Ci- 6 haloalkoxy;
  • R , R R R , R° and R' are, independently from each other, hydrogen, halogen, Ci_ 6 alkyl or Ci-6alkoxy;
  • A is heteroaryl, heteroarylalkyl or heteroarylthio.
  • R 1 is hydrogen, halogen, Ci- 6 alkyl, Ci- 6 haloalkyl or Ci- 6 alkoxy;
  • R , R R R , R° and R' are, independently from each other, hydrogen, Ci- 6 alkyl or Ci-6alkoxy;
  • A is heteroaryl or heteroarylalkyl.
  • Especially preferred compounds of formula I according to the invention are those wherein
  • R 1 is hydrogen, halogen, Ci- 6 alkyl or Ci- 6 alkoxy
  • R , R R R , R° and R' are, independently from each other, hydrogen, Ci- 6 alkyl or Ci-6alkoxy;
  • A is heteroaryl or heteroarylalkyl.
  • the compounds of formula 1.1 wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I can be obtained by transformation of a compound of formula 1.2, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and Hal is halogen, preferably bromine or chlorine, with a reducing agent such as Bu 3 SnH and a palladium catalyst.
  • the compounds of formula II wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I can be obtained by transformation of a compound of formula 1.2, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, with a reduction agent such as hydrogen and a catalyst such as palladium on charcoal or raney-nickel, or with zinc and acetic acid.
  • the compounds of formula 1.2 wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, can be obtained by transformation of a compound of formula III, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I with a phosphorus oxyhalide, e.g. phosphorus oxychloride or phosphorus oxybromide, or a thionyl halide, e.g. thionyl chloride or thionyl bromide.
  • a phosphorus oxyhalide e.g. phosphorus oxychloride or phosphorus oxybromide
  • thionyl halide e.g. thionyl chloride or thionyl bromide.
  • the compounds of formula III, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein R 1 , R 2 and A are as defined for formula I with an anthranilic acid of formula V, wherein R 4 , R 5 , R 6 and R 7 are as defined for formula I and a base, such sodium hydride, sodium methylate, sodium ethylate or potassium methylate.
  • the compound of formula III wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I can be obtained by transformation of a compound of formula XII wherein R 1 , R 2 and A are as defined for formula I and R 8 is hydrogen or Ci-Cealkyl with an anthranilic amide of formula Va, wherein R 4 , R 5 , R 6 and R 7 are as defined for formula I in a two-step procedure using a coupling reagent such as DCC, BOP or TBTU followed by treatment with a base such as NaOH in an alcoholic solvent.
  • a coupling reagent such as DCC, BOP or TBTU
  • the anthranilic acid compounds of formula V are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the compounds of formula IV, wherein R 1 , R 2 and A are as defined for formula I can be obtained by transformation of a compound of formula VI, wherein R 1 , R 2 and A are as defined for formula I with a cyanide, such as sodium cyanide, potassium cyanide or trimethylsilylcyanide and a base, such as triethylamine, ethyldiisopropylamine or pyridine.
  • a cyanide such as sodium cyanide, potassium cyanide or trimethylsilylcyanide
  • a base such as triethylamine, ethyldiisopropylamine or pyridine.
  • the compounds of formula VI, wherein R 1 , R 2 and A are as defined for formula I can be obtained by transformation of a compound of formula VII, wherein R 1 , R 2 and A are as defined for formula I with an oxidatizing agent, such as meta- chloroperbenzoic acid, hydrogen peroxide or oxone.
  • an oxidatizing agent such as meta- chloroperbenzoic acid, hydrogen peroxide or oxone.
  • the mono- and disubstituted pyridines of formula VII are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the compounds of formula 1.1, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I can be obtained by transformation of a compound of formula VIII, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I with an oxidation agent, such as 2,3-dichloro-5,6-dicycano-p-benzoquinone, oxygen, man anese(IV) oxide or ammonium cerium(IV) nitrate.
  • an oxidation agent such as 2,3-dichloro-5,6-dicycano-p-benzoquinone, oxygen, man anese(IV) oxide or ammonium cerium(IV) nitrate.
  • the compounds of formula VIII, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I can be obtained by transformation of a compound of formula IX, wherein R 1 , R 2 and A are as defined for formula I with a compound of formula X, wherein R 4 , R 5 , R 6 and R 7 are as defined for formula I, and thionyl chloride and a base, such as triethylamine, ethyldiisopropylamine or pyridine.
  • the 2-aminobenzylamines of formula X are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the compounds of formula IX, wherein R 1 , R 2 and A are as defined for formula I can be obtained by transformation of a compound of formula XI, wherein R 1 , R 2 and A are as defined for formula I with N,N'-dicyclohexylcarbodiimide, dimethylsulfoxide and an acid, such as phosphoric acid, hydrochloric acid or sulfuric acid, or with manganese dioxide or 2,3-dichloro-5,6-dicycano-p-benzoquinone.
  • the compounds of formula XI, wherein R 1 , R 2 and A are as defined for formula I can be obtained by transformation of a compound of formula XII, wherein R 1 , R 2 and A are as defined for formula I and R 8 is hydrogen or Ci-Cealkyl, with an reducing agent, such as sodium borohydride, lithium aluminium hydride, lithium borohydride or diisobutylaluminum hydride.
  • an reducing agent such as sodium borohydride, lithium aluminium hydride, lithium borohydride or diisobutylaluminum hydride.
  • the compounds of formula XII wherein R 1 , R 2 and A are as defined for formula I and R 8 is hydrogen or Ci-Cealkyl, can be obtained by transformation of a compound of formula IV, wherein R 1 , R 2 and A are as defined for formula I with a base, such as sodium methoxide, sodium ethoxide, potassium methoxide or potassium ethoxide in an alcohol and subsequent treatment with an acid, such as hydrochloric acid or sulfuric acid.
  • a base such as sodium methoxide, sodium ethoxide, potassium methoxide or potassium ethoxide
  • an acid such as hydrochloric acid or sulfuric acid.
  • the compounds of formula 1.1 wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I can be obtained by transformation of a compound of formula XIII, wherein R 1 , R 2 and A are as defined for formula I, or a salt of it, with a benzaldehyde of formula XIV, wherein R 4 , R 5 , R 6 and R 7 are as defined for formula I and R 9 is a halogen, such as fluoro, chloro or bromo, or an amino group, and a base, such as sodium carbonate, sodium bicarbonate or potassium carbonate.
  • a halogen such as fluoro, chloro or bromo
  • a base such as sodium carbonate, sodium bicarbonate or potassium carbonate.
  • the 2-halobenzaldehydes of formula XIV are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the compounds of formula 1.3 wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and R 10 is Ci- 6 alkyl can be obtained by reaction of a compound of formula 1.2, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, with an alcohol R 10 -OH and a base, such as sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide.
  • the compounds of formula 1.4 wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and R is Ci- 6 alkyl can be obtained by alkylation of a compound of formula 1.2, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, with an organometallic species, such as methylmagnesium chloride, methylmagnesium bromide,
  • the compounds of formula IIw wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and R 10 is Ci- 6 alkyl can be obtained by alkylation of a compound of formula 1.1, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I, with an organometallic species, such as methylmagnesium chloride, methylmagnesium bromide or alkyllithium.
  • organometallic species such as methylmagnesium chloride, methylmagnesium bromide or alkyllithium.
  • the compounds of formula 1.4, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and R 10 is Ci- 6 alkyl can be obtained by transformation of a compound of formula IIw, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 and A are as defined for formula I and R 10 is Ci- 6 alkyl with an oxidating agent, such as 2,3-dichloro-5,6- dicycano-p-benzoquinone, oxygen, manganese(IV) oxide or ammonium cerium(IV) nitrate.
  • an oxidating agent such as 2,3-dichloro-5,6- dicycano-p-benzoquinone, oxygen, manganese(IV) oxide or ammonium cerium(IV) nitrate.
  • the compounds of formula I wherein R , R , R , R , R , R , R and A are as defined for formula I can be obtained by transformation of a compound of formula XV, wherein R 1 , R 2 and A are as defined for formula I and R 11 is In, MgCl, MgBr, ZnCl, ZnBr, SnR 10 3 or B(OR 8 ) 2 with a compound of formula XVI,
  • R R R , R° and R' are as defined for formula I, R is hydrogen or Ci- C 6 alkyl and R 12 is a halogen, preferably chloro, bromo or iodo or a sulfonic ester such as a mesylate or tosylate and a catalyst, such as tetrakistriphenylphosphine, palladium dichloride, [1, l-bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride.
  • a catalyst such as tetrakistriphenylphosphine, palladium dichloride, [1, l-bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride.
  • the metallo-substituted pyridines of formula XV and the 2-haloquinazolines of formula XVI are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the compounds of formula I wherein R , R , R , R , R , R , R and A are as defined for formula I can be obtained by transformation of a compound of formula XVII, wherein R 1 , R 2 and A are as defined for formula I and R 12 is a halogen, preferably chloro, bromo or iodo or a sulfonic ester such as a mesylate or tosylate with a compound of formula XVIII, wherein R 3 , R 4 , R 5 , R 6 and R 7 are as defined for formula I, R 11 is In, MgCl, MgBr, ZnCl, ZnBr, SnR 10 3 or B(OR 8 ) 2 and R* is hydrogen or Ci-C 6 alkyl and a catalyst, such as tetrakistriphenylphosphine, palladium di chloride, [1, l-bis(diphenylphosphino)ferrocene]d
  • the di- and tri- substituted pyridines of formula XVII and the 2-metallo-substituted quinazolines of formula XVIII are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the reactions to give compounds of formula I are advantageously carried out in aprotic inert organic solvents or in a mixture of aprotic inert organic solvents and water.
  • Such solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles such as acetonitrile or propionitrile, amides such as N,N-dimethylformamide, diethylformamide or N-methylpyrrolidinone.
  • the reaction temperatures are advantageously between -20°C and +120°C.
  • the reactions are slightly exothermic and, as a rule, they can be carried out at ambient temperature.
  • the mixture may be heated briefly to the boiling point of the reaction mixture.
  • the reaction times can also be shortened by adding a few drops of base as reaction catalyst.
  • Suitable bases are, in particular, tertiary amines such as trimethylamine, triethylamine, quinuclidine, l,4-diazabicyclo[2.2.2]octane, l,5-diazabicyclo[4.3.0]non-5-ene or 1,5-diazabicyclo- [5.4.0]undec-7-ene.
  • inorganic bases such as hydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g. sodium hydroxide or potassium hydroxide, carbonates, e.g. sodium carbonate and potassium carbonate, hydrogen carbonates, e.g. potassium hydrogen carbonate and sodium hydrogen carbonate, or phosphates, e.g. potassium phosphate, sodium phosphate, may also be used as bases.
  • the bases can be used as such or else with catalytic amounts of a phase-transfer catalyst, for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt.
  • the compounds of formula I and, where appropriate, the tautomers thereof, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
  • the compounds of formula I according to the invention have, for practical purposes, a very advantageous spectrum of activities for protecting useful plants against diseases that are caused by phytopathogenic microorganisams, such as fungi, bacteria or viruses.
  • the invention therefore also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I is applied as active ingredient to the plants, to parts thereof or the locus thereof.
  • the compounds of formula I according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants.
  • the compounds of formula I can be used to inhibit or destroy the diseases that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
  • compounds of formula I as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
  • the compounds of formula I according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.
  • the compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia,
  • Basidiomycetes e.g. Rhizoctonia, Hemileia, Puccinia. Additionally, they are also effective against the Ascomycetes classes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara). Furthermore, the novel compounds of formula I are effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp, Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus). The compounds of formula I are also effective against Asian soybean rust (Phakopsora pachyrhizi).
  • useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco
  • useful plants is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate- synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO
  • herbicides like bromoxynil or classes of herbicides
  • ALS inhibitors for example primisulfuron, prosulfuron and trifloxysulfuron
  • EPSPS (5-enol-pyrovyl-shikimate-3-phosphate- synthase) inhibitors
  • GS glutamine synthetase
  • protoporphyrinogen-oxidase inhibitors as a result of conventional methods of breeding or genetic engineering.
  • mutagenesis is Clearfield® summer rape (Canola).
  • crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®.
  • plant or “useful plants” as used herein includes seedlings, bushes and trees.
  • crops is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
  • Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as ⁇ -endotoxins, e.g. CrylAb, CrylAc, CrylF, CrylFa2, Cry2Ab, Cry3A, Cry3Bbl or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vipl, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp.
  • insecticidal proteins from Bacillus cereus or Bacillus popilliae
  • Bacillus thuringiensis such as ⁇ -endotoxins, e.g. CrylAb, CrylAc, CrylF, CrylFa2, Cry2Ab, Cry3A, Cry3Bbl or Cry9
  • Xenorhabdus spp. such as Photorhabdus luminescens, Xenorhabdus nematophilus
  • toxins produced by animals such as scorpion toxins, arachnid toxins, wasp toxins and other insect- specific neurotoxins
  • toxins produced by fungi such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins
  • agglutinins proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors
  • ribosome- inactivating proteins (RIP) such as ricin, maize-RIP, abrin, luffin, saporin or bryodin
  • steroid metabolism enzymes such as 3 -hydroxy steroidoxidase, ecdysteroid-UDP-glycosyl- transferase, cholesterol oxidases, e
  • ⁇ -endotoxins for example CrylAb, CrylAc, CrylF, CrylFa2, Cry2Ab, Cry3A, Cry3Bbl or Cry9C, or vegetative insecticidal proteins (Vip), for example Vipl, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced
  • Truncated toxins for example a truncated CrylAb
  • modified toxins one or more amino acids of the naturally occurring toxin are replaced.
  • non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
  • Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
  • the processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • Cryl- type deoxyribonucleic acids and their preparation are known, for example, from WO
  • the toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects.
  • insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
  • Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available.
  • YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bbl toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bbl toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a CrylFa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylAc toxin); Bollgard I® (cotton variety that expresses a CrylAc toxin); Bollgard II® (cotton variety that expresses a CrylAc and a Cry2Ab toxin
  • transgenic crops are:
  • MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150
  • MON 863 expresses a Cry3Bbl toxin and has resistance to certain Coleoptera insects.
  • NK603 MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810.
  • NK603 ⁇ 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 CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
  • Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).
  • Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds).
  • Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.
  • Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events).
  • seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
  • Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
  • output traits e.g. improved storage stability, higher nutritional value and improved flavour.
  • useful plants is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225).
  • PRPs pathogenesis-related proteins
  • Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191.
  • the methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • locus of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil.
  • An example for such a locus is a field, on which crop plants are growing.
  • plant propagation material is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material” is understood to denote seeds.
  • the compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.
  • the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
  • compounds of formula I and inert carriers are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances.
  • the methods of application such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.
  • compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
  • Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers.
  • Such carriers are for example described in WO 97/33890.
  • the compounds of formula I or compositions comprising a compound of formula I as acitve ingredient and an inert carrier, can be applied to the locus of the plant or plant to be treated, simultaneously or in succession with further compounds.
  • further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
  • a preferred method of applying a compound of formula I, or a composition, comprising a compound of formula I as acitve ingredient and an inert carrier is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen.
  • the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • the compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
  • a formulation i.e. a composition comprising the compound of formula I and, if desired, a solid or liquid adjuvant or, if desired as well, a further, other biocidally active ingredient, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
  • extenders for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
  • TX means "one compound selected from the group consisting of the compounds of formulae Tl .1.1 to Ti l .1.500 described in Tables 1 to 11 of the present invention, thus the abbreviation "TX' means at least one compound selected from the compounds Tl .1.1 to Ti l .1.500:
  • the compound of formula I (herein after abbreviated by the term "TX” thus means a compound encompassed by the compounds of formula I, or preferably the term “TX” refers to a compound selected from the Tables 1 to 12, A, B and C) 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 (insect, acarine, mollusc and nematode pesticide), fungicide, synergist, herbicide, safener or plant growth regulator where appropriate.
  • a pesticide insect, acarine, mollusc and nematode pesticide
  • fungicide fungicide
  • synergist synergist
  • herbicide herbicide
  • safener plant growth regulator
  • An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; provide a composition demonstrating better plant/crop tolerance by reducing phytotoxicity; provide a composition controlling insects in their different development stages; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the TX; or help to overcome or prevent the development of resistance to individual components.
  • the particular additional active ingredient will depend upon the intended utility of the composition.
  • Suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or
  • 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;
  • Carbamates including aryl carbamates
  • pirimicarb triazamate
  • cloethocarb carbofuran
  • furathiocarb furathiocarb
  • ethiofencarb aldicarb
  • thiofurox carbosulfan
  • bendiocarb fenobucarb
  • propoxur methomyl or oxamyl
  • Benzoyl ureas such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or chlorfluazuron;
  • e)Organic tin compounds such as cyhexatin, fenbutatin oxide or azocyclotin
  • f) Pyrazoles such as tebufenpyrad and fenpyroximate
  • Macrolides such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, or spinosad, spinetoram or
  • Organochlorine compounds such as endosulfan, benzene hexachloride, DDT, chlordane or dieldrin;
  • Amidines such as chlordimeform or amitraz
  • Fumigant agents such as chloropicrin, dichloropropane, methyl bromide or metam
  • Neonicotinoid compounds such as imidacloprid, thiacloprid, acetamiprid, clothianidin, nitenpyram, dinotefuran or thiamethoxam;
  • Diacylhydrazines such as tebufenozide, chromafenozide or methoxyfenozide
  • Diphenyl ethers such as diofenolan or pyriproxifen
  • 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
  • TX refers to a compound covered by the compounds of formula I or preferably the term “TX” refers to a compound selected from the Tables 1 to 12, A, B and C; and the following List shows specific examples of mixtures comprising thecomponent TX and the component (B):
  • an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX,
  • an acaricide selected from the group of substances consisting of l,l-bis(4-chloro- phenyl)-2-ethoxyethanol (IUPAC name) (910) + TX, 2,4-dichlorophenyl
  • benzenesulfonate (IUPAC/Chemical Abstracts name) (1059) + TX, 2-fluoro-N- methyl-N-l-naphthylacetamide (IUPAC name) (1295) + TX, 4-chlorophenyl phenyl sulfone (IUPAC name) (981) + TX, abamectin (1) + TX, acequinocyl (3) + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, alpha-cypermethrin (202) + TX, amidithion (870) + TX, amidoflumet [CCN] + TX, amidothioate (872) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, aramite (881)
  • phosphamidon (639) + TX, phoxim (642) + TX, pirimiphos-methyl (652) + TX, polychloroterpenes (traditional name) (1347) + TX, polynactins (alternative name) (653) + TX, proclonol (1350) + TX, profenofos (662) + TX, promacyl (1354) + TX, propargite (671) + TX, propetamphos (673) + TX, propoxur (678) + TX,
  • prothidathion (1360) + TX, prothoate (1362) + TX, pyrethrin I (696) + TX, pyrethrm II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, quinalphos (711) + TX, quintiofos (1381) + TX, R- 1492 (development code) (1382) + TX, RA-17
  • development code (development code) (1383) + TX, rotenone (722) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, sophamide (1402) + TX, spirodiclofen (738) + TX, spiromesifen (739) + TX, SSI- 121 (development code) (1404) + TX, sulfiram
  • an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (101 1) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX,
  • an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1 122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX,
  • a bactericide selected from the group of substances consisting of 1 -hydroxy- IH- pyridine-2-thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2- ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1105) + TX, dodicin (1112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX,
  • streptomycin (744) + TX, streptomycin sesqui sulfate (744) + TX, tecloftalam (766) + TX, and thiomersal (alternative name) [CCN] + TX,
  • a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Hopkins (scientific name) (5
  • Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, Hippodamia convergens (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491) + TX, Mamestra brassicae NPV (alternative name) (494) + TX, Metaphycus helvolus (alternative name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var.
  • Steinernema bibionis (alternative name) (742) + TX, Steinernema carpocapsae (alternative name) (742) + TX, Steinernema feltiae (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp.
  • a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfluron (alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa
  • an insect pheromone selected from the group of substances consisting of (£)-dec-5- en- 1 -yl acetate with (£)-dec-5-en- 1 -ol (IUPAC name) (222) + TX, (£)-tridec-4-en- 1 - yl acetate (IUPAC name) (829) + TX, (£)-6-methylhept-2-en-4-ol (IUPAC name) (541) + TX, (£,Z)-tetradeca-4,10-dien-l-yl acetate (IUPAC name) (779) + TX, (Z)- dodec-7-en-l-yl acetate (IUPAC name) (285) + TX, (Z)-hexadec-l l-enal (IUPAC name) (436) + TX, (Z)-hexadec-l 1-en-l-yl acetate (IUPAC name) (437) + TX, (Z hex
  • an insect repellent selected from the group of substances consisting of 2-(octylthio)- ethanol (IUPAC name) (591) + TX, butopyronoxyl (933) + TX,
  • an insecticide selected from the group of substances consisting of 1-dichloro-l- nitroethane (IUPAC/Chemical Abstracts name) (1058) + TX, l, l-dichloro-2,2-bis(4- ethylphenyl)ethane (IUPAC name) (1056), + TX, 1,2-dichloropropane
  • bioethanomethrin [CCN] + TX, biopermethrin (908) + TX, bioresmethrin (80) + TX, bis(2-chloroethyl) ether (IUPAC name) (909) + TX, bistrifluron (83) + TX, borax (86) + TX, brofenvalerate (alternative name) + TX, bromfenvinfos (914) + TX, bromocyclen (918) + TX, bromo-DDT (alternative name) [CCN] + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bufencarb (924) + TX, buprofezin (99) + TX, butacarb (926) + TX, butathiofos (927) + TX, butocarboxim (103) + TX, butonate (932) + TX, butoxycarboxim (104)
  • methoxyfenozide (535) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, methylchloroform (alternative name) [CCN] + TX, methylene chloride [CCN] + TX, metofluthrin [CCN] + TX, metolcarb (550) + TX, metoxadiazone (1288) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, mirex (1294) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naftalofos (alternative name) [CCN] + T
  • phosphorothioate (1074) + TX, ⁇ , ⁇ -diethyl O-6-methyl-2- propylpyrimidin-4-yl phosphorothioate (IUPAC name) (1075) + TX, ⁇ , ⁇ , ⁇ ', ⁇ '- tetrapropyl dithiopyrophosphate (IUPAC name) (1424) + TX, oleic acid (IUPAC name) (593) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydemeton-methyl (609) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp'-DDT (219) + TX, para-dichlorobenzene [CCN] + TX, parathion (615) + TX, parathion-methyl (616) + TX, penfluron (alternative name) [CCN] + TX, pen
  • polychloroterpenes (traditional name) (1347) + TX, potassium arsenite [CCN] + TX, potassium thiocyanate [CCN] + TX, prallethrin (655) + TX, precocene I (alternative name) [CCN] + TX, precocene II (alternative name) [CCN] + TX, precocene III (alternative name) [CCN] + TX, primidophos (1349) + TX, profenofos (662) + TX, profluthrin [CCN] + TX, promacyl (1354) + TX, promecarb (1355) + TX, propaphos (1356) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothiofos (686) + TX, prothoate (1362) + TX, protrifenbute [CCN
  • pyresmethnn (1367) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridalyl (700) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, pyriproxyfen (708) + TX, quassia (alternative name) [CCN] + TX, quinalphos (711) + TX, quinalphos-methyl (1376) + TX, quinothion (1380) + TX, quintiofos (1381) + TX, R-1492 (development code) (1382) + TX, rafoxanide (alternative name) [CCN] + TX, resmethrin (719) + TX, rot
  • a nematicide selected from the group of substances consisting of AKD-3088
  • a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,
  • a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar- ⁇ -methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX,
  • a rodenticide selected from the group of substances consisting of 2-isovalerylindan- 1,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (
  • an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX,
  • a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX,
  • a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX,
  • azaconazole 60207-31-0] + TX, bitertanol [70585-36-3] + TX, bromuconazole [116255-48-2] + TX, cyproconazole [94361-06-5] + TX, difenoconazole [119446-68-3] + TX, diniconazole [83657-24-3] + TX, epoxiconazole [106325-08-0] + TX, fenbuconazole [114369-43-6] + TX, fluquinconazole [136426-54-5] + TX, flusilazole [85509-19-9] + TX, flutriafol [76674-21-0] + TX, hexaconazole [79983-71-4] + TX, imazalil
  • the components (B) are known.
  • the references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number.
  • the above described mixing partners are known.
  • the active ingredients are included in "The Pesticide Manual” [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council]
  • they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound “abamectin” is described under entry number (1).
  • [CCN] is added hereinabove to the particular compound, the compound in question is included in the "Compendium of Pesticide Common Names", which is accessible on the internet [A.
  • component (B) in combination with component TX surprisingly and substantially may enhance the effectiveness of the latter against fungi, and vice versa. Additionally, the method of the invention is effective against a wider spectrum of such fungi that can be combated with the active ingredients of this method, when used solely.
  • the weight ratio of component TX to component (B) is from 2000 : 1 to 1 : 1000.
  • a non-limiting example for such weight ratios is compound of formula I :
  • compound of formula B (component (B)) is 10: 1.
  • the weight ratio of component TX to component (B) is preferably from 100 : 1 to 1 : 100; more preferably from 20 : 1 to 1 : 50.
  • the active ingredient mixture of component TX to component (B) comprises compounds of formula I and a further, other biocidally active ingredients or compositions or if desired, a solid or liquid adjuvant preferably in a mixing ratio of from 1000: 1 to 1 : 1000, especially from 50: 1 to 1 :50, more especially in a ratio of from 20: 1 to 1 :20, even more especially from 10: 1 to 1 : 10, very especially from 5: 1 and 1 :5, special preference being given to a ratio of from 2: 1 to 1 :2, and a ratio of from 4: 1 to 2: 1 being likewise preferred, above all in a ratio of 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
  • compositions wherein component TX and component (B) are present in the composition in amounts producing a synergistic effect.
  • This synergistic activity is apparent from the fact that the fungicidal activity of the composition comprising component TX and component (B) is greater than the sum of the fungicidal activities of component TX and of component (B).
  • This synergistic activity extends the range of action of component TX and component (B) in two ways.
  • synergism corresponds to a positive value for the difference of (O-E).
  • expected activity said difference (O-E) is zero.
  • a negative value of said difference (O-E) signals a loss of activity compared to the expected activity.
  • the compositions according to the invention can also have further surprising advantageous properties.
  • Such advantageous properties are: more advantageuos degradability; improved toxicological and/or ecotoxicological behaviour; or improved characteristics of the useful plants including: emergence, crop yields, more developed root system, tillering increase, increase in plant height, bigger leaf blade, less dead basal leaves, stronger tillers, greener leaf colour, less fertilizers needed, less seeds needed, more productive tillers, earlier flowering, early grain maturity, less plant verse (lodging), increased shoot growth, improved plant vigor, and early germination.
  • compositions according to the invention have a systemic action and can be used as foliar, soil and seed treatment fungicides.
  • compositions according to the invention it is possible to inhibit or destroy the phytopathogenic microorganisms which occur in plants or in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different useful plants, while at the same time the parts of plants which grow later are also protected from attack by
  • compositions according to the invention can be applied to the phytopathogenic microorganisms, the useful plants, the locus thereof, the propagation material thereof, storage goods or technical materials threatened by microorganism attack.
  • compositions according to the invention may be applied before or after infection of the useful plants, the propagation material thereof, storage goods or technical materials by the microorganisms.
  • a further aspect of the present invention is a method of controlling diseases on useful plants or on propagation material thereof caused by phytopathogens, which comprises applying to the useful plants, the locus thereof or propagation material thereof a composition according to the invention.
  • Preferred is a method, which comprises applying to the useful plants or to the locus thereof a composition according to the invention, more preferably to the useful plants.
  • a method which comprises applying to the propagation material of the useful plants a composition according to the invention.
  • composition stands for the various mixtures or combinations of components TX and (B), for example in a single “ready- mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days.
  • the order of applying the components TX and (B) is not essential for working the present invention.
  • compositions according to the invention may also comprise more than one of the active components (B), if, for example, a broadening of the spectrum of disease control is desired. For instance, it may be advantageous in the agricultural practice to combine two or three components (B) with component TX.
  • An example is a composition comprising a compound of formula (I), azoxystrobin and cyproconazole. Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from lOg to 1kg a.i./ha, most preferably from 20g to 600g a.i./ha.
  • convenient rates of application are from lOmg to lg of active substance per kg of seeds.
  • the rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.
  • the compounds of formula (I), or a pharmaceutical salt thereof, described above may also have an advantageous spectrum of activity for the treatment and/or prevention of microbial infection in an animal.
  • “Animal” can be any animal, for example, insect, mammal, reptile, fish, amphibian, preferably mammal, most preferably human.
  • Treatment means the use on an animal which has microbial infection in order to reduce or slow or stop the increase or spread of the infection, or to reduce the infection or to cure the infection.
  • prevention means the use on an animal which has no apparent signs of microbial infection in order to prevent any future infection, or to reduce or slow the increase or spread of any future infection.
  • a compound of formula (I) in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal.
  • a compound of formula (I) as a pharmaceutical agent.
  • a compound of formula (I) as an antimicrobial agent in the treatment of an animal.
  • a pharmaceutical agent for use in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal.
  • composition comprising as an active ingredient a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.
  • This composition can be used for the treatment and/or prevention of antimicrobial infection in an animal.
  • This pharmaceutical composition can be in a form suitable for oral administration, such as tablet, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions dispersible powders, dispersible granules, syrups and elixirs.
  • this pharmaceutical composition can be in a form suitable for topical application, such as a spray, a cream or lotion.
  • this pharmaceutical composition can be in a form suitable for parenteral administration, for example injection.
  • this pharmaceutical composition can be in inhalable form, such as an aerosol spray.
  • the compounds of formula (I) may be effective against various microbial species able to cause a microbial infection in an animal.
  • microbial species are those causing Aspergillosis such as Aspergillus fumigatus, A. flavus, A. terms, A. nidulans and niger, those causing Blastomycosis such as Blastomyces dermatitidis; those causing Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and C. lusitaniae; those causing Coccidioidomycosis such as Coccidioides immitis; those causing Cryptococcosis such as Cryptococcus
  • neoformans those causing Histoplasmosis such as Histoplasma capsulatum and those causing Zygomycosis such as Absidia corymbifera, Rhizomucor pusillus and Rhizopus arrhizus.
  • Fusarium Spp such as Fusarium oxysporum and Fusarium solani
  • Scedosporium Spp such as Scedosporium apiospermum and Scedosporium prolifwans.
  • Example 1 The preparation of 2-(3'-fluoro-[2,4']bipyridinyl-6-yl)-quinazoline (Compound T 1.1.176) a) Preparation of 2-(6-bromopyridin-2-yl)-l,2,3,4-tetrahydroquinazoline A solution of pyridine (5.1 g, 64 mmol) in 50 ml of dichloromethane is added to a solution of thionyl chloride (7.6 g, 64 mmol) in 50 ml of dichloromethane at 0 °C.
  • 2,3-Dichloro-5,6-dicycano-p-benzoquinone (121 g, 0.53 mol) is added to a suspension of 2-(6-bromopyridin-2-yl)-l,2,3,4-tetrahydroquinazoline (77 g, 0.26 mol) in 1450 ml of toluene.
  • the reaction mixture is stirred for 30 min at room temperature, basified with sodium hydroxide solution (5 M in water) and extracted with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure.
  • Example 2 This example illustrates the preparation of 2-[6-(6-chloro-pyridin-3- ylmethyl)-pyridin-2-yl]-quinazoline (Compound Tl .1.321)
  • Tetrakis(triphenylphosphin)palladium (231 mg, 0.2 mmol) is added and the mixture is stirred for 30 min at 65 °C. 4 ml of a 2-chloro-5-pyridylmethylzinc bromide solution (0.5 M in tetrahydrofurane) are added and the reaction mixture is heated to reflux for 2 h. Subsequently the mixture is cooled and 250 ml of a EDTA solution (12 % in water) are added and the mixture is stirred for further 16 h at room temperature, then diluted with 1 N aqueous sodium hydroxide solution and extracted with ethyl acetate.
  • a 2-chloro-5-pyridylmethylzinc bromide solution 0.5 M in tetrahydrofurane
  • Example 3 This example illustrates the preparation of 2-(6-Pyridin-2-ylethynyl- pyridin-2-yl)-quinazoline (Compound Tl .1.346)
  • a mixture of 2-(6-bromopyridin-2-yl)-quinazoline (200 mg, 0.70 mmol), 2- ethynylpyridine (225 mg, 1.75 mmol) and diisopropylamine (141 mg, 1.40 mmol) in dimethylformamide (4 ml) is degassed with argon for 5 min. Copper(I) iodide (13 mg, 0.07 mmol) and bis(triphenylphosphine)palladiumdichloride are added to the mixture.
  • the vial is sealed and heated under microwave conditions at 160°C. Subsequently the mixture is cooled and a EDTA solution (12 % in water) are added and the mixture is stirred for further 16 h at room temperature, then diluted with 1 N aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure.
  • Example 4 This example illustrates the preparation of 2-[6-(pyridin-2-yloxy)-pyridin- 2-yl]-quinazoline (Compound Tl .1.376)
  • Example 5 This example illustrates the preparation of 2-[6-(4-methyl-pyrimidin-2- ylsulfanyl)-pyridin-2-yl]-quinazoline (Compound Tl .1.476)
  • a mixture of 2-(6-bromopyridin-2-yl)-quinazoline (200 mg, 0.7 mmol), 2- mercapto-4-methylpyrimidine (125 mg, 0.77 mmol) and potassium carbonate (245 mg, 1.8 mmol) in 10 ml of ⁇ , ⁇ -dimethylformamide is heated under argon for 8 h at 110 °C. Subsequently the mixture is cooled, diluted with brine and extracted with ethyl acetate.
  • Table 1 This table discloses the 500 compounds T 1.1.1 to T 1.1.500 of formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A. l . 500 of Table A.
  • the specific compound Tl .1.23 is the compound of the formula Tl, in which each of the of the variables A, R 1 and R 2 has the specific meaning given in the line A.1.23 of the Table A and the compound Tl .1.23
  • Table 2 This table discloses the 500 compounds T2.1.1 to T2.1.500 of the formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • Table 5 This table discloses the 500 compounds T5.1.1 to T5.1.500 of the formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • Table 7 This table discloses the 500 compounds T7.1.1 to T7.1.500 of the formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • Table 8 This table discloses the 500 compounds T8.1.1 to T8.1.500 of the formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • Table 9 This table discloses the 500 compounds T9.1.1 to T9.1.500 of the formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • Table 10 This table discloses the 500 compounds TIO.1.1 to T10.1.500 of the formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • Table 11 This table discloses the 500 compounds Ti l .1.1 to Ti l .1.500 of the formula
  • each of the of the variables A, R 1 and R 2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
  • Table 12 shows selected m.p. data and selected LC/MS data for compounds of Tables 1 to 11. Throughout this description, temperatures are given in degrees Celsius and "m.p.” means melting point. LC/MS means Liquid Chromatography Mass
  • Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
  • Example F-2 Emulsifiable concentrate
  • Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
  • the novel compound is dissolved in dichloromethane, the solution is sprayed onto the carrier and the solvent is then removed by distillation under vacuum.
  • Example F7 Flowable concentrate for seed treatment
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by
  • microorganisms by spraying, pouring or immersion.
  • Tomato leaf disks cv. Baby were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 2 days after application.
  • the inoculated leaf disks were incubated at 23 °C / 21°C (day/night) and 80% rh under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check disk leaf disks (5 - 7 days after application).
  • Biological Example 2 fungicidal activity against Blumeria graminis f. sp. tritici (Erysiphe graminis f. sp. tritici) I wheat / leaf disc preventative (Powdery mildew on wheat)
  • Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated by shaking powdery mildew infected plants above the test plates 1 day after application.
  • the inoculated leaf disks were incubated at 20°C and 60% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate chamber and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check leaf segments (6 - 8 days after application).
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application.
  • DMSO fetal sulfate
  • Tl.1.7 Ti l l 1, Tl.1.16, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.31, Tl.1.32, Tl.1.36, Tl.1.37, Tl.1.42, Tl.1.49, Tl.1.54, Tl.1.61, Tl.1.66, Tl.1.67, Tl.1.71, Tl.1.104, Tl.1.107, Tl.1.109, Tl.1.114, Tl.1.121, Tl.1.122, Tl.1.124, Tl.1.126, Tl.1.131, Tl.1.132, Tl.1.136, Tl.1.137, Tl.1.139, Tl.1.142, Tl.1.144, Tl.1.154, Tl.1.159, Tl.1.161, Tl.1.167, Tl.1.169, Tl.1.172, Tl.1.179, Tl.1.184, Tl.1.196, Tl.1.244, Tl.1.257, Tl.1.266,
  • Mycelial fragments of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores iss added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
  • nutrient broth PDB potato dextrose broth
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was measured photometrically 3-4 days after application.
  • nutrient broth PDB potato dextrose broth
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
  • nutrient broth PDB potato dextrose broth
  • Biological Example 8 fungicidal activity against Mycosphaerella graminicola (Septoria tritici) I liquid culture (Septoria blotch)
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
  • nutrient broth PDB potato dextrose broth
  • Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 2 days after application.
  • the inoculated test leaf disks were incubated at 20°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5-7 days after application).
  • Tomato leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks were incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5-7 days after application).
  • Grape vine leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks were incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application).
  • T 1.1.29, T 1.1.49, T 1.1.54 and T 1.1.104 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
  • Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf segments were incubated at 19°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 - 9 days after application).
  • Biological Example 13 fungicidal activity against Pyrenophora teres I barley / leaf disc preventative (Net blotch) Barley leaf segments cv. Hasso were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segmens were inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments were incubated at 20°C and 65% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5-7 days after application).
  • Mycelia fragments of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format), the nutrient broth containing the fungal material was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application.
  • Tl.l.131, Tl.l.137, Tl.l.142, Tl.l.172, Tl.1.266, Tl.l.326, Tl.1.431, Tl.1.432, Tl.l.441 and T3.1.137 and from table 13 compound 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

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Abstract

Compounds of formula I (I) wherein the other substituents R1, R2, R3, R4, R5 and R6 are as defined in claim 1, and their use as microbicides.

Description

SUBSTITUTED QUINAZOLINES AS FUNGICIDES
The present invention relates to novel quinazoline containing compounds, their use in compositions and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
The incidence of serious microbial infections, particularly fungal infections, either systemic or topical, continues to increase for plants.
Fungicides are compounds, of natural or synthetic origin, which act to protect plants against damage caused by fungi. Current methods of agriculture rely heavily on the use of fungicides. In fact, some crops cannot be grown usefully without the use of fungicides. Using fungicides allows a grower to increase the yield of the crop and consequently, increase the value of the crop. Numerous fungicidal agents have been developed. However, the treatment of fungal infestations continues to be a major problem. Furthermore, fungicide resistance has become a serious problem, rendering these agents ineffective for some agricultural uses. As such, a need exists for the development of new fungicidal compounds.
Accordingly, the present invention provides a compound of formula I:
Figure imgf000002_0001
wherein: R1 is hydrogen, halogen, cyano, Ci-6alkyl, C3-6cycloalkyl, Ci-6haloalkyl, Ci-6alkoxy, Ci-6haloalkoxy or Ci-6alkylthio;
2 3 4 5 6 1
R , R R R , R° and R' are, independently from each other, hydrogen, hydroxy, halogen, Ci-6alkyl, C3-6cycloalkyl or Ci-6alkoxy;
A is heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio or heteroarylalkynyl; or a salt or a N-oxide thereof.
1 2 3 4 5 6 1
Unless otherwise stated, the substituents A, R , R , R , R , R , R and R are unsubstituted or substituted. When the substituents are unsubstituted then they are preferably substituted by the substituents given below, wherein the meaning of the
1 2 3 4 5 6 1
substiuents for the substituents A, R , R , R , R , R , R and R is given directly with the meaning of the substituents A, R1, R2, R3, R4, R5, R6 and R7.
The invention covers all agronomically acceptable salts, isomers, structural isomers, stereoisomers, diastereoisomers, enantiomers, tautomers and N-oxides of those compounds. The compounds of formula I may exist in different geometric or optical isomeric forms or in different tautomeric forms. One or more centres of chirality may be present, in which case compounds of the formula I may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of diastereomers. There may be double bonds present in the molecule, such as C=C or C=N bonds, in which case compounds of formula I may exist as single isomers or mixtures of isomers. Centres of tautomerisation may be present. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. Also atropisomerism may occur as a result of a restricted rotation abaout a single bond.
Suitable salts of the compounds of formula I include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid. Other examples of organic carboxylic acids include haloacids such as trifluoroacetic acid. N-oxides are oxidised forms of tertiary amines or oxidised forms of nitrogen containing heteroaromatic compounds. They are described in many books for example in "Heterocyclic N-oxides" by Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Florida, 1991.
The alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, ^-propyl, «-butyl, n- pentyl, «-hexyl, z'so-propyl, «-butyl, sec-butyl, zso-butyl or tert-butyl. Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned. The alkenyl and alkynyl groups can be mono- or di-unsaturated. The cycloalkyl groups are, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine more preferably chlorine or fluorine. This also applies, correspondingly, to halogen in combination with other meanings, such as halogenalkyl or halogenalkoxy. Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms and comprise at least one halogen atom up to perhalogenated alkyle group. Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, l, l-difluoro-2,2,2-trichloroethyl, 2,2,3, 3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl. Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy; preferably methoxy and ethoxy. Halogenalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1, 1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2- difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy. Thioalkyl is, for example, methylthio, ethylthio, propylthio, tert-butylthio, hexylthio. Alkylamino is, for example, methylamino, ethylamino, propylamino, tert-butylamino, hexylamino as well as, for example dimethylamino, diethylamino, dipropylamino, ditert-butylamino, dihexylamino or trimethylamino, triethylamino, tripropylamino, tri tert-butylamino, trihexylamino or 2- to 3-fold substituted amines with different alkyl groups. The preferred substituents of the substituted alkyl groups, the substituted cycloalkyl groups, the substituted alkenyl groups, the substituted alkynyl groups and the substituted alkoxy group in the compound of formula (I) are selected from the following substituents F, CI, Br, I, -OH, -CN, nitro, -Ci-4alkoxy, -C1-4 alkylthio, -
17R18 where R 17 and R 1180 are independently H, -Ci-4alkyl or substituted -Ci-4alkyl or combine with the interjacent nitrogen to form a five- or six-membered ring which may comprise one or two or three heteroatoms (one or two N, O or S atoms in addition to the interjacent nitrogen atom), in which case the heterocyclic ring is unsubstituted or the heterocyclic ring is substituted by one or two C1-4 alkyl groups, - C(0)H, -C(0)(Ci-4 alkyl), -C(0)(Ci-4 alkoxy), -C(0) H2, -C(0) H(Ci-4 alkyl), - C(0)N(Ci-4 alkyl)(Ci-4 alkyl), -OC(0) H(Ci-4 alkyl), -OC(0)N(Ci-4 alkyl)(Ci-4 alkyl), - HC(0)(Ci-4 alkyl),- HC(0)(Ci-4 alkoxy), -N(Ci-4 alkyl )C(0)(Ci-4 alkyl), -N(Ci-4 alkyl )C(0)(Ci-4 alkoxy), -OC(O) (CM alkyl ), -OC(0)(Ci-4 alkoxy), -Si(C1-4 alkyl)3, -Si(Ci_4 alkoxy)3, aryl, aryloxy, -(Ci-s - perhaloalkyl) , arylCi-4alkynyl, -Ci_ 6alkynyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, aryl groups are either substituted or unsubstituted, preferably these substituents of the substituted groups bear only one further substituent, more preferably are these substituents of the substituted groups not further substituted.
The more preferred substituents of the substituted alkyl groups are selected from the following substituents -OH, CN, F, CI, Ci-4alkoxy, Ci-4alkylamino. The alkyl groups are branched or linear. The most preferred alkyl groups are methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl (2-methylpropyl), pentyl, 1-methylpentyl, 1- ethylpentyl, iso-pentyl (3-methylbutyl), hexyl, heptyl, octyl, or nonyl.
Preferably the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than two further substituents, more preferably the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than one further substituent, most preferred the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) are not further substituted. "Heteroaryl" refers to aromatic ring systems comprising mono-, bi- or tricyclic systems wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member. The term "Heteroaryl" may mean substituted or unsubstituted heteroaryl unless otherwise indicated and hence the heteroaryl moieties may be unsubstituted or substituted with one or more of the same or different substituents. Representative examples of heteroaryl include, for example, benzimidazolyl,
benzo[l,2,5]thiadiazolyl, benzofuranyl, benzothiazolyl, benzothiophenyl,
benzotriazolyl, benzoxazolyl, cinnolinyl, dibenzofuranyl, furyl, imidazolyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazinyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazinyl and triazolyl.
Suitably, substituents for "hetreoaryl" groups may be selected from the list including aryl, cycloalkyl, cycloalkenyl and heterocyclic moiety containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure, halogen, alkyl, haloalkyl, cycloalkyl,
cycloalkylalkyl, alkenyl, haloalkenyl, cycloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, cycloalkyloxy, haloalkenyloxy, haloalkynyloxy, alkylthio, haloalkylthio, cycloalkylthio, alkyl carbonyl, haloalkylcarbonyl, cycloalkylcarbonyl,
alkenyl carbonyl, alkynylcarbonyl, formyl, alkoxyalkyl, cyano, nitro, hydroxy, mercapto, amino, alkylamino, dialkylamino, -C(0)(Ci-4 alkoxy), -C(0)NH2, - C(0) H(Ci-4 alkyl), -C(0)N(Ci-4 alkyl)(CM alkyl), -OC(0) H(Ci-4 alkyl), - OC(0)N(Ci-4 alkyl)(Ci-4 alkyl) ,- HC(0)(Ci-4 alkyl),- HC(0)(Ci-4 alkoxy), -N(Ci. 4 alkyl )C(0)(Ci-4alkyl), -N(Ci-4 alkyl )C(0)(Ci-4 alkoxy), -OC(O) (Ci-4 alkyl ), - OC(0)(Ci-4 alkoxy), -Si(C1-4 alkyl)3, -Si(C1-4 alkoxy)3, and aryloxy. Preferred substituents are aryl, cycloalkyl, cycloalkenyl and heterocyclic moiety containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-s cycloalkyl, halo, Ci-4 haloalkyl, Ci-4 alkoxy, Ci-4 haloalkoxy, -C(0)(Ci-4 alkoxy), - C(0)(Ci-4 alkyl), -C(0)H, Ci-4 alkylthio, Ci-4 haloalkylthio nitro and cyano and are more preferably halogen (in particular, fluoro or chloro), cyano, alkyl (in particular, methyl and ethyl), haloalkyl (in particular, trifluoromethyl), alkoxy (in particular, methoxy or ethoxy), haloalkoxy, methylthio, halomethylthio, -C(0)(methoxy), formyl and acetyl.
"Heteroarylalkyl" means a radical -RaRb where Ra is an alkylene group and Rb is an unsubstituted or substituted heteroaryl group as defined above;
"Heteroarylalkynyl" means a radical -RaRb where Ra is an alkynylene group as defined below and Rb is an unsubstituted or substituted heteroaryl group as defined above. "Heteroaryloxy" means a radical -OR, wherein R is an heteroaryl group as defined above. "Heteroarylthio" means a radical -SR, where R is an heteroaryl group as defined above
Preferably the groups defined above when used alone or as part of a compound term (e.g. alkyl when used alone or as part of, for example, haloalkyl) may be unsubstituted or substituted by one or more substituents. In particular, alkyl, alkoxy, haloalkyl, haloalkoxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio and heteroarylalkynyl groups may be unsubstituted or substituted.
Suitably, these optional substituents (if not indicated otherwise) are independently selected from halogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, haloalkenyl, cycloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, cycloalkyloxy, haloalkenyloxy, haloalkynyloxy, alkylthio, haloalkylthio,
cycloalkylthio, alkyl carbonyl, haloalkylcarbonyl, cycloalkylcarbonyl,
alkenyl carbonyl, alkynylcarbonyl, alkoxyalkyl, cyano, nitro, hydroxy, mercapto, amino, alkylamino, dialkylamino, aryl, cycloalkyl, cycloalkenyl and heterocyclic moiety containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure. Preferred substituents are alkyl, alkenyl, alkynyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy and cyano and are more preferably halogen (in particular, fluoro or chloro), cyano, alkyl (in particular, methyl and ethyl), haloalkyl (in particular, trifluoromethyl), alkoxy (in particular, methoxy or ethoxy),haloalkoxy, aryl, cycloalkyl, cycloalkenyl and heterocyclic moiety containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure.. The compounds of formula I may exist in different geometric or optical isomeric forms or in different tautomeric forms. One or more centres of chirality may be present, in which case compounds of the formula I may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of
diastereomers. There may be double bonds present in the molecule, such as C=C or C=N bonds, in which case compounds of formula I may exist as single isomers or mixtures of isomers. Centres of tautomerisation may be present. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. Also atropisomerism may occur as a result of arestricted rotation abaout a single bond.
Suitable salts of the compounds of formula I include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid. Other examples of organic carboxylic acids include haloacids such as trifluoroacetic acid.
In the preferred compounds of the formula (I) the preferred alkyl groups and the preferred alkoxy groups are methyl, ethyl, propyl, methoxy and ethoxy groups. Methyl, ethyl and methoxy groups are very particularly preferred.
In particularly preferred embodiments of the invention, the preferred groups
1 2 3 4 5 6 1
for A, R , R , R R R , R° and R' in any combination thereof, are as set out below. Preferably R1 is hydrogen, halogen, cyano, Ci-6alkyl, C3-6cycloalkyl, Ci-6haloalkyl, Ci-6alkoxy or Ci-6haloalkoxy; more preferably R1 is hydrogen, halogen, Ci-6alkyl, Ci_ 6haloalkyl, Ci-6alkoxy or Ci-6haloalkoxy; even more preferably R1 is hydrogen, halogen, Ci-6alkyl, Ci-6haloalkyl or Ci-6alkoxy; most preferabley R1 is hydrogen, halogen, Ci-6alkyl or Ci-6alkoxy;
2 3 4 5 6 1
R , R R R , R° and R' are, independently from each other, hydrogen, halogen, Ci_
2 3 4 5 6 1
6alkyl, C3-6cycloalkyl, or Ci-6alkoxy; preferably R , R , R , R , R and R are, independently from each other, hydrogen, halogen or Ci-6alkoxy;
Preferably A is heteroaryl, heteroarylalkyl, heteroarylthio or heteroalkynyl, more preferably A is heteroaryl, heteroarylalkyl or heteroarylthio, even more preferably A is heteroaryl or heteroarylalkyl. Most preferred optionally substituted heteroaryl moiety in the subtituents A are furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrazolyl, pyridyl, quinolinyl, pynmidinyl, benzooxazolyl, benzothiazolyl, indazolyl, benzo[l,2,5]oxadiazolyl, benzo[l,2,5]thiadiazolyl, or dibenzofuranyl and especially preferred optionally substituted substituents A are furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrazolyl, pyridyl, quinolinyl, pyrimidinyl, benzooxazolyl, benzothiazolyl, indazolyl, benzo[l,2,5]oxadiazolyl, benzo[l,2,5]thiadiazolyl, or dibenzofuranyl
Preferred compounds of formula I according to the invention are those wherein R1 is hydrogen, halogen, cyano, Ci-6alkyl, C3-6cycloalkyl, Ci-6haloalkyl, Ci-6alkoxy or Ci-6haloalkoxy;
2 3 4 5 6 1
R , R R R , R° and R' are, independently from each other, hydrogen, halogen, Ci_ 6alkyl, C3-6cycloalkyl or Ci-6alkoxy; and
A is heteroaryl, heteroarylalkyl, heteroarylthio or heteroalkynyl.
More preferred compounds of formula I according to the invention are those wherein R1 is hydrogen, halogen, cyano, Ci-6alkyl, Ci-6haloalkyl, Ci-6alkoxy or Ci_
6haloalkoxy;
2 3 4 5 6 1
R , R , R , R , R and R are, independently from each other, hydrogen, halogen, Ci_ 6alkyl or Ci-6alkoxy; and
A is heteroaryl, heteroarylalkyl, heteroarylthio or heteroalkynyl. Even more preferred compounds of formula I according to the invention are those wherein
R1 is hydrogen, halogen, Ci-6alkyl, Ci-6haloalkyl, Ci-6alkoxy or Ci-6haloalkoxy;
2 3 4 5 6 1
R , R R R , R° and R' are, independently from each other, hydrogen, halogen, Ci_ 6alkyl or Ci-6alkoxy; and
A is heteroaryl, heteroarylalkyl or heteroarylthio.
Most preferred compounds of formula I according to the invention are those wherein R1 is hydrogen, halogen, Ci-6alkyl, Ci-6haloalkyl or Ci-6alkoxy;
2 3 4 5 6 1
R , R R R , R° and R' are, independently from each other, hydrogen, Ci-6alkyl or Ci-6alkoxy; and
A is heteroaryl or heteroarylalkyl. Especially preferred compounds of formula I according to the invention are those wherein
R1 is hydrogen, halogen, Ci-6alkyl or Ci-6alkoxy;
2 3 4 5 6 1
R , R R R , R° and R' are, independently from each other, hydrogen, Ci-6alkyl or Ci-6alkoxy; and
A is heteroaryl or heteroarylalkyl.
Compounds of formula (I) can be made as shown in the following schemes. The compounds of formula 1.1, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula II, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I with an oxidation agent, such as 2,3-dichloro-5,6-dicycano-p-benzoquinone, oxygen, manganese(IV) oxide or ammonium cerium(IV) nitrate.
Figure imgf000011_0001
The compounds of formula 1.1, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula 1.2, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and Hal is halogen, preferably bromine or chlorine, with a reducing agent such as Bu3SnH and a palladium catalyst.
Figure imgf000011_0002
The compounds of formula II, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula 1.2, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, with a reduction agent such as hydrogen and a catalyst such as palladium on charcoal or raney-nickel, or with zinc and acetic acid.
Figure imgf000011_0003
The compounds of formula 1.2, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, can be obtained by transformation of a compound of formula III, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I with a phosphorus oxyhalide, e.g. phosphorus oxychloride or phosphorus oxybromide, or a thionyl halide, e.g. thionyl chloride or thionyl bromide.
Figure imgf000012_0001
The compounds of formula III, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein R1, R2 and A are as defined for formula I with an anthranilic acid of formula V, wherein R4, R5, R6 and R7 are as defined for formula I and a base, such sodium hydride, sodium methylate, sodium ethylate or potassium methylate.
Figure imgf000012_0002
Alternatively, the compound of formula III wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula XII wherein R1, R2 and A are as defined for formula I and R8 is hydrogen or Ci-Cealkyl with an anthranilic amide of formula Va, wherein R4, R5, R6 and R7 are as defined for formula I in a two-step procedure using a coupling reagent such as DCC, BOP or TBTU followed by treatment with a base such as NaOH in an alcoholic solvent.
Figure imgf000013_0001
The anthranilic acid compounds of formula V are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
The compounds of formula IV, wherein R1, R2 and A are as defined for formula I can be obtained by transformation of a compound of formula VI, wherein R1, R2 and A are as defined for formula I with a cyanide, such as sodium cyanide, potassium cyanide or trimethylsilylcyanide and a base, such as triethylamine, ethyldiisopropylamine or pyridine.
Figure imgf000013_0002
The compounds of formula VI, wherein R1, R2 and A are as defined for formula I can be obtained by transformation of a compound of formula VII, wherein R1, R2 and A are as defined for formula I with an oxidatizing agent, such as meta- chloroperbenzoic acid, hydrogen peroxide or oxone.
Figure imgf000013_0003
The mono- and disubstituted pyridines of formula VII are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar. Alternatively, the compounds of formula 1.1, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula VIII, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I with an oxidation agent, such as 2,3-dichloro-5,6-dicycano-p-benzoquinone, oxygen, man anese(IV) oxide or ammonium cerium(IV) nitrate.
Figure imgf000014_0001
(VIII) (1.1)
The compounds of formula VIII, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula IX, wherein R1, R2 and A are as defined for formula I with a compound of formula X, wherein R4, R5, R6 and R7 are as defined for formula I, and thionyl chloride and a base, such as triethylamine, ethyldiisopropylamine or pyridine.
Figure imgf000014_0002
The 2-aminobenzylamines of formula X are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar. The compounds of formula IX, wherein R1, R2 and A are as defined for formula I can be obtained by transformation of a compound of formula XI, wherein R1, R2 and A are as defined for formula I with N,N'-dicyclohexylcarbodiimide, dimethylsulfoxide and an acid, such as phosphoric acid, hydrochloric acid or sulfuric acid, or with manganese dioxide or 2,3-dichloro-5,6-dicycano-p-benzoquinone.
DCC,
DMSO,
Figure imgf000015_0001
The compounds of formula XI, wherein R1, R2 and A are as defined for formula I can be obtained by transformation of a compound of formula XII, wherein R1, R2 and A are as defined for formula I and R8 is hydrogen or Ci-Cealkyl, with an reducing agent, such as sodium borohydride, lithium aluminium hydride, lithium borohydride or diisobutylaluminum hydride.
Figure imgf000015_0002
The compounds of formula XII, wherein R1, R2 and A are as defined for formula I and R8 is hydrogen or Ci-Cealkyl, can be obtained by transformation of a compound of formula IV, wherein R1, R2 and A are as defined for formula I with a base, such as sodium methoxide, sodium ethoxide, potassium methoxide or potassium ethoxide in an alcohol and subsequent treatment with an acid, such as hydrochloric acid or sulfuric acid.
Figure imgf000016_0001
Alternatively the compounds of formula 1.1, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I can be obtained by transformation of a compound of formula XIII, wherein R1, R2 and A are as defined for formula I, or a salt of it, with a benzaldehyde of formula XIV, wherein R4, R5, R6 and R7 are as defined for formula I and R9 is a halogen, such as fluoro, chloro or bromo, or an amino group, and a base, such as sodium carbonate, sodium bicarbonate or potassium carbonate.
Figure imgf000016_0002
The 2-halobenzaldehydes of formula XIV are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
The compounds of formula XIII, wherein R1, R2 and A are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein R1, R2 and A are as defined for formula I with ammonia.
Figure imgf000016_0003
The compounds of formula 1.3, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and R10 is Ci-6alkyl can be obtained by reaction of a compound of formula 1.2, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, with an alcohol R10-OH and a base, such as sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide.
Figure imgf000017_0001
The compounds of formula 1.4, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and R is Ci-6alkyl can be obtained by alkylation of a compound of formula 1.2, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and Hal is halogen, preferably chlorine or bromine, with an organometallic species, such as methylmagnesium chloride, methylmagnesium bromide,
trimethylaluminum or R10B(OR8)2 or trimethylboroxine.
Figure imgf000017_0002
Alternatively, the compounds of formula IIw, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and R10 is Ci-6alkyl can be obtained by alkylation of a compound of formula 1.1, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I, with an organometallic species, such as methylmagnesium chloride, methylmagnesium bromide or alkyllithium.
Figure imgf000018_0001
The compounds of formula 1.4, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and R10 is Ci-6alkyl can be obtained by transformation of a compound of formula IIw, wherein R1, R2, R4, R5, R6, R7 and A are as defined for formula I and R10 is Ci-6alkyl with an oxidating agent, such as 2,3-dichloro-5,6- dicycano-p-benzoquinone, oxygen, manganese(IV) oxide or ammonium cerium(IV) nitrate.
Figure imgf000018_0002
1 2 3 4 5 6 7
Alternatively the compounds of formula I, wherein R , R , R , R , R , R , R and A are as defined for formula I can be obtained by transformation of a compound of formula XV, wherein R1, R2 and A are as defined for formula I and R11 is In, MgCl, MgBr, ZnCl, ZnBr, SnR10 3 or B(OR8)2 with a compound of formula XVI,
3 4 5 6 7 8
wherein R R R , R° and R' are as defined for formula I, R is hydrogen or Ci- C6alkyl and R12 is a halogen, preferably chloro, bromo or iodo or a sulfonic ester such as a mesylate or tosylate and a catalyst, such as tetrakistriphenylphosphine, palladium dichloride, [1, l-bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride.
Figure imgf000019_0001
(XV)
(XVI) (I)
The metallo-substituted pyridines of formula XV and the 2-haloquinazolines of formula XVI are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
1 2 3 4 5 6 7
Alternatively the compounds of formula I, wherein R , R , R , R , R , R , R and A are as defined for formula I can be obtained by transformation of a compound of formula XVII, wherein R1, R2 and A are as defined for formula I and R12 is a halogen, preferably chloro, bromo or iodo or a sulfonic ester such as a mesylate or tosylate with a compound of formula XVIII, wherein R3, R4, R5, R6 and R7 are as defined for formula I, R11 is In, MgCl, MgBr, ZnCl, ZnBr, SnR10 3 or B(OR8)2 and R* is hydrogen or Ci-C6alkyl and a catalyst, such as tetrakistriphenylphosphine, palladium di chloride, [1, l-bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride.
Figure imgf000019_0002
(XVII) (XVI II)
The di- and tri- substituted pyridines of formula XVII and the 2-metallo-substituted quinazolines of formula XVIII are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar. The reactions to give compounds of formula I are advantageously carried out in aprotic inert organic solvents or in a mixture of aprotic inert organic solvents and water. Such solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles such as acetonitrile or propionitrile, amides such as N,N-dimethylformamide, diethylformamide or N-methylpyrrolidinone. The reaction temperatures are advantageously between -20°C and +120°C. In general, the reactions are slightly exothermic and, as a rule, they can be carried out at ambient temperature. To shorten the reaction time, or else to start the reaction, the mixture may be heated briefly to the boiling point of the reaction mixture. The reaction times can also be shortened by adding a few drops of base as reaction catalyst. Suitable bases are, in particular, tertiary amines such as trimethylamine, triethylamine, quinuclidine, l,4-diazabicyclo[2.2.2]octane, l,5-diazabicyclo[4.3.0]non-5-ene or 1,5-diazabicyclo- [5.4.0]undec-7-ene. However, inorganic bases such as hydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g. sodium hydroxide or potassium hydroxide, carbonates, e.g. sodium carbonate and potassium carbonate, hydrogen carbonates, e.g. potassium hydrogen carbonate and sodium hydrogen carbonate, or phosphates, e.g. potassium phosphate, sodium phosphate, may also be used as bases. The bases can be used as such or else with catalytic amounts of a phase-transfer catalyst, for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt.
The compounds of formula I and, where appropriate, the tautomers thereof, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
It has now been found that the compounds of formula I according to the invention have, for practical purposes, a very advantageous spectrum of activities for protecting useful plants against diseases that are caused by phytopathogenic microorganisams, such as fungi, bacteria or viruses. The invention therefore also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I is applied as active ingredient to the plants, to parts thereof or the locus thereof. The compounds of formula I according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants. The compounds of formula I can be used to inhibit or destroy the diseases that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
It is also possible to use compounds of formula I as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
Furthermore, the compounds of formula I according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.
The compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia,
Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria) and
Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara). Furthermore, the novel compounds of formula I are effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp, Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus). The compounds of formula I are also effective against Asian soybean rust (Phakopsora pachyrhizi).
Within the scope of the invention, useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.
The term "useful plants" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate- synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO
(protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding
(mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®.
The term "plant" or "useful plants" as used herein includes seedlings, bushes and trees. The term "crops" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as δ-endotoxins, e.g. CrylAb, CrylAc, CrylF, CrylFa2, Cry2Ab, Cry3A, Cry3Bbl or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vipl, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect- specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome- inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3 -hydroxy steroidoxidase, ecdysteroid-UDP-glycosyl- transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases. In the context of the present invention there are to be understood by δ-endotoxins, for example CrylAb, CrylAc, CrylF, CrylFa2, Cry2Ab, Cry3A, Cry3Bbl or Cry9C, or vegetative insecticidal proteins (Vip), for example Vipl, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced
recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated CrylAb, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073. The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl- type deoxyribonucleic acids and their preparation are known, for example, from WO
95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available.
Examples of such plants are: YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bbl toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bbl toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a CrylFa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylAc toxin); Bollgard I® (cotton variety that expresses a CrylAc toxin); Bollgard II® (cotton variety that expresses a CrylAc and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a CrylAb toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); NatureGard® , Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Btl 1 corn borer (CB) trait) and Protecta®.
Further examples of such transgenic crops are:
1. Btll Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR 96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated CrylAb toxin. Btl 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Btl76 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR 96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer {Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CrylAb toxin. Btl76 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150
Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bbl toxin and has resistance to certain Coleoptera insects.
5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-l 160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein CrylF for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603 MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 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 CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.
Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
The term "locus" of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.
The term "plant propagation material" is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.
The compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.
Therefore the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
To this end compounds of formula I and inert carriers are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects. Suitable carriers and adjuvants (auxiliaries) can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890. The compounds of formula I or compositions, comprising a compound of formula I as acitve ingredient and an inert carrier, can be applied to the locus of the plant or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
A preferred method of applying a compound of formula I, or a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, i.e. a composition comprising the compound of formula I and, if desired, a solid or liquid adjuvant or, if desired as well, a further, other biocidally active ingredient, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active compounds (surfactants). The following mixtures of the compounds of TX with a further active ingredient (B) are preferred (the abbreviation "TX" means "one compound selected from the group consisting of the compounds of formulae Tl .1.1 to Ti l .1.500 described in Tables 1 to 11 of the present invention, thus the abbreviation "TX' means at least one compound selected from the compounds Tl .1.1 to Ti l .1.500:
The compound of formula I (herein after abbreviated by the term "TX" thus means a compound encompassed by the compounds of formula I, or preferably the term "TX" refers to a compound selected from the Tables 1 to 12, A, B and C) 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 (insect, acarine, mollusc and nematode pesticide), fungicide, synergist, herbicide, safener or plant growth regulator where appropriate. The activity of the compositions according to the invention may thereby be broadened considerably and may have surprising advantages which can also be described, in a wider sense, as synergistic activity. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; provide a composition demonstrating better plant/crop tolerance by reducing phytotoxicity; provide a composition controlling insects in their different development stages; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the TX; or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition. Examples of suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or
5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl-
3-(2-oxothiolan-3-ylidenemethyl)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;
c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl;
d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or chlorfluazuron;
e)Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin; f) Pyrazoles, such as tebufenpyrad and fenpyroximate;
g) Macrolides, such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, or spinosad, spinetoram or
azadirachtin;
h) Hormones or pheromones;
i) Organochlorine compounds such as endosulfan, benzene hexachloride, DDT, chlordane or dieldrin;
j) Amidines, such as chlordimeform or amitraz;
k) Fumigant agents, such as chloropicrin, dichloropropane, methyl bromide or metam; 1) Neonicotinoid compounds such as imidacloprid, thiacloprid, acetamiprid, clothianidin, nitenpyram, dinotefuran or thiamethoxam;
m) Diacylhydrazines, such as tebufenozide, chromafenozide or methoxyfenozide; n) Diphenyl ethers, such as diofenolan or pyriproxifen;
o) Indoxacarb;
p) Chlorfenapyr;
q) Pymetrozine or pyrifluquinazon;
r) Spirotetramat, spirodiclofen or spiromesifen;
s) Flubendiamide, chloranthraliniprole, or cyanthraniliprole;
t) Cyenopyrafen or cyflumetofen; or
u) Sulfoxaflor.
In addition to the major chemical classes of pesticide listed above, other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition. For instance, selective insecticides for particular crops, for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed. Alternatively insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron). The following mixtures of the compounds of formula I with active ingredients are preferred, wherein, preferably, the term "TX" refers to a compound covered by the compounds of formula I or preferably the term "TX" refers to a compound selected from the Tables 1 to 12, A, B and C; and the following List shows specific examples of mixtures comprising thecomponent TX and the component (B):
an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX,
an acaricide selected from the group of substances consisting of l,l-bis(4-chloro- phenyl)-2-ethoxyethanol (IUPAC name) (910) + TX, 2,4-dichlorophenyl
benzenesulfonate (IUPAC/Chemical Abstracts name) (1059) + TX, 2-fluoro-N- methyl-N-l-naphthylacetamide (IUPAC name) (1295) + TX, 4-chlorophenyl phenyl sulfone (IUPAC name) (981) + TX, abamectin (1) + TX, acequinocyl (3) + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, alpha-cypermethrin (202) + TX, amidithion (870) + TX, amidoflumet [CCN] + TX, amidothioate (872) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, aramite (881) + TX, arsenous oxide (882) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azobenzene (IUPAC name) (888) + TX, azocyclotin (46) + TX, azothoate (889) + TX, benomyl (62) + TX, benoxafos (alternative name) [CCN] + TX, benzoximate (71) + TX, benzyl benzoate (IUPAC name) [CCN] + TX, bifenazate (74) + TX, bifenthrin (76) + TX, binapacryl (907) + TX, brofenvalerate (alternative name) + TX, bromocyclen (918) + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bromopropylate (94) + TX, buprofezin (99) + TX, butocarboxim (103) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, calcium poly sulfide (IUPAC name) (111) + TX, camphechlor (941) + TX, carbanolate (943) + TX, carbaryl (115) + TX, carbofuran (118) + TX, carbophenothion (947) + TX, CGA 50'439 (development code) (125) + TX, chino- methionat (126) + TX, chlorbenside (959) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorfenapyr (130) + TX, chlorfenethol (968) + TX, chlorfenson (970) + TX, chlorfensulphide (971) + TX, chlorfenvinphos (131) + TX, chlorobenzilate (975) + TX, chloromebuform (977) + TX, chloromethiuron (978) + TX, chloropropylate (983) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, clofentezine (158) + TX, closantel (alternative name) [CCN] + TX, coumaphos (174) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos (1010) + TX, cufraneb (1013) + TX, cyanthoate (1020) + TX, cyflumetofen (CAS Reg. No. : 400882-07-7) + TX, cyhalothrin (196) + TX, cyhexatin (199) + TX, cypermethrin (201) + TX, DCPM (1032) + TX, DDT (219) + TX, demephion (1037) + TX, demephion-0 (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton-0 (1038) + TX, demeton-O-methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulphon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diazinon (227) + TX, dichlofluanid (230) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicofol (242) + TX, dicrotophos (243) + TX, dienochlor (1071) + TX, dimefox (1081) + TX, dimethoate (262) + TX, dinactin (alternative name) (653) + TX, dinex (1089) + TX, dinex-diclexine (1089) + TX, dinobuton (269) + TX, dinocap (270) + TX, dinocap-4 [CCN] + TX, dinocap-6 [CCN] + TX, dinocton (1090) + TX, dinopenton (1092) + TX, dinosulfon (1097) + TX, dinoterbon (1098) + TX, dioxathion (1102) + TX, diphenyl sulfone (IUPAC name) (1103) + TX, disulfiram (alternative name) [CCN] + TX, disulfoton (278) + TX, DNOC (282) + TX, dofenapyn (1113) + TX, doramectin (alternative name) [CCN] + TX, endosulfan (294) + TX, endothion (1121) + TX, EPN (297) + TX, eprinomectin (alternative name) [CCN] + TX, ethion (309) + TX, ethoate-methyl (1134) + TX, etoxazole (320) + TX, etrimfos (1142) + TX, fenazaflor (1147) + TX, fenazaquin (328) + TX, fenbutatin oxide (330) + TX, fenothiocarb (337) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fenpyroximate (345) + TX, fenson (1157) + TX, fentrifanil (1161) + TX, fenvalerate (349) + TX, fipronil (354) + TX, fluacrypyrim (360) + TX, fluazuron (1166) + TX, flubenzimine (1167) + TX, fluey cloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1 169) + TX, flufenoxuron (370) + TX, flumethrin (372) + TX, fluorbenside (1174) + TX, fluvalinate (1184) + TX, FMC 1137 (development code) (1185) + TX, formetanate (405) + TX, formetanate hydrochloride (405) + TX, formothion (1192) + TX, formparanate (1193) + TX, gamma-HCH (430) + TX, glyodin (1205) + TX, halfenprox (424) + TX, heptenophos (432) + TX, hexadecyl cyclopropanecarboxylate (IUPAC/Chemical Abstracts name) (1216) + TX, hexythiazox (441) + TX, iodomethane (IUPAC name) (542) + TX, isocarbophos (alternative name) (473) + TX, isopropyl O-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, lindane (430) + TX, lufenuron (490) + TX, malathion (492) + TX, malonoben (1254) + TX, mecarbam (502) + TX, mephosfolan (1261) + TX, mesulfen (alternative name) [CCN] + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methidathion (529) + TX, methiocarb (530) + TX, methomyl (531) + TX, methyl bromide (537) + TX, metolcarb (550) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naled (567) + TX, NC-184 (compound code) + TX, NC-512 (compound code) + TX, nifluridide (1309) + TX, nikkomycins (alternative name) [CCN] + TX, nitrilacarb (1313) + TX, nitrilacarb 1 : 1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp'-DDT (219) + TX, parathion (615) + TX, permethrin (626) + TX, petroleum oils (alternative name) (628) + TX, phenkapton (1330) + TX, phenthoate (631) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX,
phosphamidon (639) + TX, phoxim (642) + TX, pirimiphos-methyl (652) + TX, polychloroterpenes (traditional name) (1347) + TX, polynactins (alternative name) (653) + TX, proclonol (1350) + TX, profenofos (662) + TX, promacyl (1354) + TX, propargite (671) + TX, propetamphos (673) + TX, propoxur (678) + TX,
prothidathion (1360) + TX, prothoate (1362) + TX, pyrethrin I (696) + TX, pyrethrm II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, quinalphos (711) + TX, quintiofos (1381) + TX, R- 1492 (development code) (1382) + TX, RA-17
(development code) (1383) + TX, rotenone (722) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, sophamide (1402) + TX, spirodiclofen (738) + TX, spiromesifen (739) + TX, SSI- 121 (development code) (1404) + TX, sulfiram
(alternative name) [CCN] + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulphur (754) + TX, SZI-121 (development code) (757) + TX, tau-fluvalinate (398) + TX, tebufenpyrad (763) + TX, TEPP (1417) + TX, terbam (alternative name) + TX, tetrachlorvinphos (777) + TX, tetradifon (786) + TX, tetranactin (alternative name) (653) + TX, tetrasul (1425) + TX, thiafenox (alternative name) + TX, thiocarboxime (1431) + TX, thiofanox (800) + TX, thiometon (801) + TX, thioquinox (1436) + TX, thuringiensin (alternative name) [CCN] + TX, triamiphos (1441) + TX, triarathene (1443) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trifenofos (1455) + TX, trinactin (alternative name) (653) + TX, vamidothion (847) + TX, vaniliprole [CCN] and YI-5302 (compound code) + TX, an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX,
an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (101 1) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX,
an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1 122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX,
a bactericide selected from the group of substances consisting of 1 -hydroxy- IH- pyridine-2-thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2- ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1105) + TX, dodicin (1112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX,
kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308) + TX, nitrapyrin (580) + TX, octhilinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (611) + TX, potassium hydroxy quinoline sulfate (446) + TX, probenazole (658) + TX,
streptomycin (744) + TX, streptomycin sesqui sulfate (744) + TX, tecloftalam (766) + TX, and thiomersal (alternative name) [CCN] + TX,
a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51) + TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51) + TX, Bacillus thuringiensis subsp. tenebrionis (scientific name) (51) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii (alternative name) (54) + TX, Chrysoperla cornea (alternative name) (151) + TX, Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV (alternative name) (191) + TX, Dacnusa sibirica
(alternative name) (212) + TX, Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternative name) (300) + TX, Helicoverpa zea NPV (alternative name) (431) + TX,
Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, Hippodamia convergens (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491) + TX, Mamestra brassicae NPV (alternative name) (494) + TX, Metaphycus helvolus (alternative name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var. anisopliae (scientific name) (523) + TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575) + TX, Orius spp. (alternative name) (596) + TX, Paecilomyces fumosoroseus (alternative name) (613) + TX, Phytoseiulus persimilis (alternative name) (644) + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741) + TX,
Steinernema bibionis (alternative name) (742) + TX, Steinernema carpocapsae (alternative name) (742) + TX, Steinernema feltiae (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp. (alternative name) (826) + TX, Typhlodromus occidentalis (alternative name) (844) and Verticillium lecanii (alternative name) (848) + TX, a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537) + TX,
a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfluron (alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa
(alternative name) [CCN] + TX, tretamine (alternative name) [CCN] and uredepa (alternative name) [CCN] + TX,
an insect pheromone selected from the group of substances consisting of (£)-dec-5- en- 1 -yl acetate with (£)-dec-5-en- 1 -ol (IUPAC name) (222) + TX, (£)-tridec-4-en- 1 - yl acetate (IUPAC name) (829) + TX, (£)-6-methylhept-2-en-4-ol (IUPAC name) (541) + TX, (£,Z)-tetradeca-4,10-dien-l-yl acetate (IUPAC name) (779) + TX, (Z)- dodec-7-en-l-yl acetate (IUPAC name) (285) + TX, (Z)-hexadec-l l-enal (IUPAC name) (436) + TX, (Z)-hexadec-l 1-en-l-yl acetate (IUPAC name) (437) + TX, (Z hexadec-13-en-l 1-yn-l-yl acetate (IUPAC name) (438) + TX, (Z)-icos-13-en-10-one (IUPAC name) (448) + TX, (Z)-tetradec-7-en-l-al (IUPAC name) (782) + TX, (Z)- tetradec-9-en-l-ol (IUPAC name) (783) + TX, (Z)-tetradec-9-en-l-yl acetate (IUPAC name) (784) + TX, (7£,9Z)-dodeca-7,9-dien-l-yl acetate (IUPAC name) (283) + TX, (9Z, 1 l£)-tetradeca-9, l l-dien-l-yl acetate (IUPAC name) (780) + TX, (9Z, 12E)- tetradeca-9, 12-dien-l-yl acetate (IUPAC name) (781) + TX, 14-methyloctadec-l-ene (IUPAC name) (545) + TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (IUPAC name) (544) + TX, alpha- multistriatin (alternative name) [CCN] + TX, brevicomin (alternative name) [CCN] + TX, codlelure (alternative name) [CCN] + TX, codlemone (alternative name) (167) + TX, cuelure (alternative name) (179) + TX, disparlure (277) + TX, dodec-8-en-l-yl acetate (IUPAC name) (286) + TX, dodec-9- en-l-yl acetate (IUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-l-yl acetate (IUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4- methyloctanoate (IUPAC name) (317) + TX, eugenol (alternative name) [CCN] + TX, frontalin (alternative name) [CCN] + TX, gossyplure (alternative name) (420) + TX, grandlure (421) + TX, grandlure I (alternative name) (421) + TX, grandlure II (alternative name) (421) + TX, grandlure III (alternative name) (421) + TX, grandlure IV (alternative name) (421) + TX, hexalure [CCN] + TX, ipsdienol (alternative name) [CCN] + TX, ipsenol (alternative name) [CCN] + TX, japonilure (alternative name) (481) + TX, lineatin (alternative name) [CCN] + TX, litlure (alternative name) [CCN] + TX, looplure (alternative name) [CCN] + TX, medlure [CCN] + TX, megatomoic acid (alternative name) [CCN] + TX, methyl eugenol (alternative name) (540) + TX, muscalure (563) + TX, octadeca-2, 13-dien-l-yl acetate (IUPAC name) (588) + TX, octadeca-3, 13-dien-l-yl acetate (IUPAC name) (589) + TX, orfralure (alternative name) [CCN] + TX, oryctalure (alternative name) (317) + TX, ostramone (alternative name) [CCN] + TX, siglure [CCN] + TX, sordidin (alternative name) (736) + TX, sulcatol (alternative name) [CCN] + TX, tetradec-l l-en-l-yl acetate (IUPAC name) (785) + TX, trimedlure (839) + TX, trimedlure A (alternative name) (839) + TX, trimedlure Bi (alternative name) (839) + TX, trimedlure B2 (alternative name) (839) + TX, trimedlure C (alternative name) (839) and trunc-call (alternative name) [CCN] + TX,
an insect repellent selected from the group of substances consisting of 2-(octylthio)- ethanol (IUPAC name) (591) + TX, butopyronoxyl (933) + TX,
butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin
[CCN] + TX,
an insecticide selected from the group of substances consisting of 1-dichloro-l- nitroethane (IUPAC/Chemical Abstracts name) (1058) + TX, l, l-dichloro-2,2-bis(4- ethylphenyl)ethane (IUPAC name) (1056), + TX, 1,2-dichloropropane
(IUPAC/Chemical Abstracts name) (1062) + TX, 1,2-dichloropropane with 1,3- dichloropropene (IUPAC name) (1063) + TX, l-bromo-2-chloroethane
(IUPAC/Chemical Abstracts name) (916) + TX, 2,2,2-trichloro-l-(3,4-dichloro- phenyl)ethyl acetate (IUPAC name) (1451) + TX, 2,2-dichlorovinyl 2- ethylsulphinylethyl methyl phosphate (IUPAC name) (1066) + TX, 2-(l,3-dithiolan- 2-yl)phenyl dimethylcarbamate (IUPAC/ Chemical Abstracts name) (1109) + TX, 2- (2-butoxyethoxy)ethyl thiocyanate (IUPAC/Chemical Abstracts name) (935) + TX, 2- (4,5-dimethyl-l,3-dioxolan-2-yl)phenyl methylcarbamate (IUPAC/ Chemical
Abstracts name) (1084) + TX, 2-(4-chloro-3,5-xylyloxy)ethanol (IUPAC name) (986) + TX, 2-chlorovinyl diethyl phosphate (IUPAC name) (984) + TX, 2-imidazolidone (IUPAC name) (1225) + TX, 2-isovalerylindan-l,3-dione (IUPAC name) (1246) + TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate (IUPAC name) (1284) + TX, 2-thiocyanatoethyl laurate (IUPAC name) (1433) + TX, 3-bromo-l-chloroprop-l- ene (IUPAC name) (917) + TX, 3-methyl-l-phenylpyrazol-5-yl dimethylcarbamate (IUPAC name) (1283) + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate (IUPAC name) (1285) + TX, 5,5-dimethyl-3-oxocyclohex-l-enyl dimethylcarbamate (IUPAC name) (1085) + TX, abamectin (1) + TX, acephate (2) + TX, acetamiprid (4) + TX, acethion (alternative name) [CCN] + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, acrylonitrile (IUPAC name) (861) + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, aldrin (864) + TX, allethrin (17) + TX, allosamidin (alternative name) [CCN] + TX, allyxycarb (866) + TX, alpha-cypermethrin (202) + TX, alpha-ecdysone (alternative name) [CCN] + TX, aluminium phosphide (640) + TX, amidithion (870) + TX, amidothioate (872) + TX, aminocarb (873) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, anabasine (877) + TX, athidathion (883) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azadirachtin (alternative name) (41) + TX, azamethiphos (42) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azothoate (889) + TX, Bacillus thuringiensis delta endotoxins (alternative name) (52) + TX, barium hexafluorosilicate (alternative name) [CCN] + TX, barium polysulfide
(IUPAC/Chemical Abstracts name) (892) + TX, barthrin [CCN] + TX, Bayer 22/190 (development code) (893) + TX, Bayer 22408 (development code) (894) + TX, bendiocarb (58) + TX, benfuracarb (60) + TX, bensultap (66) + TX, beta-cyfluthrin (194) + TX, beta-cypermethrin (203) + TX, bifenthrin (76) + TX, bioallethrin (78) + TX, bioallethrin ^-cyclopentenyl isomer (alternative name) (79) + TX,
bioethanomethrin [CCN] + TX, biopermethrin (908) + TX, bioresmethrin (80) + TX, bis(2-chloroethyl) ether (IUPAC name) (909) + TX, bistrifluron (83) + TX, borax (86) + TX, brofenvalerate (alternative name) + TX, bromfenvinfos (914) + TX, bromocyclen (918) + TX, bromo-DDT (alternative name) [CCN] + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bufencarb (924) + TX, buprofezin (99) + TX, butacarb (926) + TX, butathiofos (927) + TX, butocarboxim (103) + TX, butonate (932) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, calcium arsenate [CCN] + TX, calcium cyanide (444) + TX, calcium polysulfide (IUPAC name) (111) + TX, camphechlor (941) + TX, carbanolate (943) + TX, carbaryl (115) + TX, carbofuran (118) + TX, carbon disulfide (IUPAC/Chemical Abstracts name) (945) + TX, carbon tetrachloride
(IUPAC name) (946) + TX, carbophenothion (947) + TX, carbosulfan (119) + TX, cartap (123) + TX, cartap hydrochloride (123) + TX, cevadine (alternative name) (725) + TX, chlorbicyclen (960) + TX, chlordane (128) + TX, chlordecone (963) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorethoxyfos (129) + TX, chlorfenapyr (130) + TX, chlorfenvinphos (131) + TX, chlorfluazuron (132) + TX, chlormephos (136) + TX, chloroform [CCN] + TX, chloropicrin (141) + TX, chlorphoxim (989) + TX, chlorprazophos (990) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, chromafenozide (150) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, cis-resmethrin (alternative name) + TX, cismethrin (80) + TX, clocythrin (alternative name) + TX, cloethocarb (999) + TX, closantel (alternative name) [CCN] + TX, clothianidin (165) + TX, copper acetoarsenite [CCN] + TX, copper arsenate [CCN] + TX, copper oleate [CCN] + TX, coumaphos (174) + TX, coumithoate (1006) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos (1010) + TX, crufomate (1011) + TX, cryolite (alternative name) (177) + TX, CS 708 (development code) (1012) + TX, cyanofenphos (1019) + TX, cyanophos (184) + TX, cyanthoate (1020) + TX, cyclethrin [CCN] + TX, cycloprothrin (188) + TX, cyfluthrin (193) + TX, cyhalothrin (196) + TX, cypermethrin (201) + TX, cyphenothrin (206) + TX, cyromazine (209) + TX, cythioate (alternative name) [CCN] + TX, <i-limonene (alternative name) [CCN] + TX, <f-tetramethrin (alternative name) (788) + TX, DAEP (1031) + TX, dazomet (216) + TX, DDT (219) + TX, decarbofuran (1034) + TX, deltamethrin (223) + TX, demephion (1037) + TX, demephion-0 (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton-0 (1038) + TX, demeton-O-methyl (224) + TX, demeton- S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulphon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diamidafos (1044) + TX, diazinon (227) + TX, dicapthon (1050) + TX, dichlofenthion (1051) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicresyl (alternative name) [CCN] + TX, dicrotophos (243) + TX, dicyclanil (244) + TX, dieldrin (1070) + TX, diethyl 5-methylpyrazol-3-yl phosphate (IUPAC name) (1076) + TX, diflubenzuron (250) + TX, dilor (alternative name) [CCN] + TX, dimefluthrin [CCN] + TX, dimefox (1081) + TX, dimetan (1085) + TX, dimethoate (262) + TX, dimethrin (1083) + TX, dimethylvinphos (265) + TX, dimetilan (1086) + TX, dinex (1089) + TX, dinex-diclexine (1089) + TX, dinoprop (1093) + TX, dinosam (1094) + TX, dinoseb (1095) + TX, dinotefuran (271) + TX, diofenolan (1099) + TX, dioxabenzofos (1100) + TX, dioxacarb (1101) + TX, dioxathion (1102) + TX, disulfoton (278) + TX, dithicrofos (1108) + TX, DNOC (282) + TX, doramectin (alternative name) [CCN] + TX, DSP (1115) + TX, ecdysterone (alternative name) [CCN] + TX, EI 1642 (development code) (1118) + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, EMPC (1120) + TX, empenthrin (292) + TX, endosulfan (294) + TX, endothion (1121) + TX, endrin (1122) + TX, EPBP (1123) + TX, EPN (297) + TX, epofenonane (1124) + TX, eprinomectin (alternative name) [CCN] + TX, esfenvalerate (302) + TX, etaphos (alternative name) [CCN] + TX, ethiofencarb (308) + TX, ethion (309) + TX, ethiprole (310) + TX, ethoate-methyl (1134) + TX, ethoprophos (312) + TX, ethyl formate (IUPAC name) [CCN] + TX, ethyl-DDD (alternative name) (1056) + TX, ethylene dibromide (316) + TX, ethylene dichloride (chemical name) (1136) + TX, ethylene oxide [CCN] + TX, etofenprox (319) + TX, etrimfos (1142) + TX, EXD (1143) + TX, famphur (323) + TX, fenamiphos (326) + TX, fenazaflor (1147) + TX, fenchlorphos (1148) + TX, fenethacarb (1149) + TX, fenfluthrin (1150) + TX, fenitrothion (335) + TX, fenobucarb (336) + TX, fenoxacrim (1153) + TX, fenoxycarb (340) + TX, fenpirithrin (1155) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fensulfothion (1158) + TX, fenthion (346) + TX, fenthion- ethyl [CCN] + TX, fenvalerate (349) + TX, fipronil (354) + TX, flonicamid (358) + TX, flubendiamide (CAS. Reg. No.: 272451-65-7) + TX, flucofuron (1168) + TX, fluey cloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1169) + TX, flufenerim [CCN] + TX, flufenoxuron (370) + TX, flufenprox (1171) + TX, flumethrin (372) + TX, fluvalinate (1184) + TX, FMC 1137 (development code) (1185) + TX, fonofos (1191) + TX, formetanate (405) + TX, formetanate
hydrochloride (405) + TX, formothion (1192) + TX, formparanate (1193) + TX, fosmethilan (1194) + TX, fospirate (1195) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furathiocarb (412) + TX, furethrin (1200) + TX, gamma-cyhalothrin (197) + TX, gamma-HCH (430) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, GY-81 (development code) (423) + TX, halfenprox (424) + TX, halofenozide (425) + TX, HCH (430) + TX, HEOD (1070) + TX, heptachlor (1211) + TX, heptenophos (432) + TX, heterophos [CCN] + TX, hexaflumuron (439) + TX, HHDN (864) + TX, hydramethylnon (443) + TX, hydrogen cyanide (444) + TX, hydroprene (445) + TX, hyquincarb (1223) + TX, imidacloprid (458) + TX, imiprothrin (460) + TX, indoxacarb (465) + TX, iodomethane (IUPAC name) (542) + TX, IPSP (1229) + TX, isazofos (1231) + TX, isobenzan (1232) + TX, isocarbophos (alternative name) (473) + TX, isodrin (1235) + TX, isofenphos (1236) + TX, isolane (1237) + TX, isoprocarb (472) + TX, isopropyl 0-(methoxyaminothiophosphoiyl)salicylate (IUPAC name) (473) + TX, isoprothiolane (474) + TX, isothioate (1244) + TX, isoxathion (480) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, juvenile hormone I (alternative name) [CCN] + TX, juvenile hormone II (alternative name) [CCN] + TX, juvenile hormone III (alternative name) [CCN] + TX, kelevan (1249) + TX, kinoprene (484) + TX, lambda-cyhalothrin (198) + TX, lead arsenate [CCN] + TX, lepimectin (CCN) + TX, leptophos (1250) + TX, lindane (430) + TX, lirimfos (1251) + TX, lufenuron (490) + TX, lythidathion (1253) + TX, w-cumenyl methylcarbamate (IUPAC name) (1014) + TX, magnesium phosphide (IUPAC name) (640) + TX, malathion (492) + TX, malonoben (1254) + TX, mazidox (1255) + TX, mecarbam (502) + TX, mecarphon (1258) + TX, menazon (1260) + TX, mephosfolan (1261) + TX, mercurous chloride (513) + TX, mesulfenfos (1263) + TX, metaflumizone (CCN) + TX, metam (519) + TX, metam-potassium (alternative name) (519) + TX, metam- sodium (519) + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methanesulphonyl fluoride (IUPAC/Chemical Abstracts name) (1268) + TX, methidathion (529) + TX, methiocarb (530) + TX, methocrotophos (1273) + TX, methomyl (531) + TX, methoprene (532) + TX, methoquin-butyl (1276) + TX, methothrin (alternative name) (533) + TX, methoxychlor (534) + TX,
methoxyfenozide (535) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, methylchloroform (alternative name) [CCN] + TX, methylene chloride [CCN] + TX, metofluthrin [CCN] + TX, metolcarb (550) + TX, metoxadiazone (1288) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, mirex (1294) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naftalofos (alternative name) [CCN] + TX, naled (567) + TX, naphthalene (IUPAC/Chemical Abstracts name) (1303) + TX, NC-170 (development code) (1306) + TX, NC-184 (compound code) + TX, nicotine (578) + TX, nicotine sulfate (578) + TX, nifluridide (1309) + TX, nitenpyram (579) + TX, nithiazine (1311) + TX, nitrilacarb (1313) + TX, nitrilacarb 1 : 1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, nornicotine (traditional name) (1319) + TX, novaluron (585) + TX, noviflumuron (586) + TX, O-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate (IUPAC name) (1057) + TX, Ο,Ο-diethyl O-4-methyl-2-oxo-2H-chromen-7-yl
phosphorothioate (IUPAC name) (1074) + TX, Ο,Ο-diethyl O-6-methyl-2- propylpyrimidin-4-yl phosphorothioate (IUPAC name) (1075) + TX, Ο,Ο,Ο',Ο'- tetrapropyl dithiopyrophosphate (IUPAC name) (1424) + TX, oleic acid (IUPAC name) (593) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydemeton-methyl (609) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp'-DDT (219) + TX, para-dichlorobenzene [CCN] + TX, parathion (615) + TX, parathion-methyl (616) + TX, penfluron (alternative name) [CCN] + TX, pentachlorophenol (623) + TX, pentachlorophenyl laurate (IUPAC name) (623) + TX, permethrin (626) + TX, petroleum oils (alternative name) (628) + TX, PH 60-38 (development code) (1328) + TX, phenkapton (1330) + TX, phenothrin (630) + TX, phenthoate (631) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX, phosnichlor (1339) + TX, phosphamidon (639) + TX, phosphine (IUPAC name) (640) + TX, phoxim (642) + TX, phoxim-methyl (1340) + TX, pirimetaphos (1344) + TX, pirimicarb (651) + TX, pirimiphos-ethyl (1345) + TX, pirimiphos-methyl (652) + TX, polychlorodicyclopentadiene isomers (IUPAC name) (1346) + TX,
polychloroterpenes (traditional name) (1347) + TX, potassium arsenite [CCN] + TX, potassium thiocyanate [CCN] + TX, prallethrin (655) + TX, precocene I (alternative name) [CCN] + TX, precocene II (alternative name) [CCN] + TX, precocene III (alternative name) [CCN] + TX, primidophos (1349) + TX, profenofos (662) + TX, profluthrin [CCN] + TX, promacyl (1354) + TX, promecarb (1355) + TX, propaphos (1356) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothiofos (686) + TX, prothoate (1362) + TX, protrifenbute [CCN] + TX, pymetrozine (688) + TX, pyraclofos (689) + TX, pyrazophos (693) + TX,
pyresmethnn (1367) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridalyl (700) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, pyriproxyfen (708) + TX, quassia (alternative name) [CCN] + TX, quinalphos (711) + TX, quinalphos-methyl (1376) + TX, quinothion (1380) + TX, quintiofos (1381) + TX, R-1492 (development code) (1382) + TX, rafoxanide (alternative name) [CCN] + TX, resmethrin (719) + TX, rotenone (722) + TX, RU 15525 (development code) (723) + TX, RU 25475 (development code) (1386) + TX, ryania (alternative name) (1387) + TX, ryanodine (traditional name) (1387) + TX, sabadilla (alternative name) (725) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, SI-0205 (compound code) + TX, SI-0404 (compound code) + TX, SI-0405 (compound code) + TX, silafluofen (728) + TX, SN 72129 (development code) (1397) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoride (IUPAC/Chemical Abstracts name) (1399) + TX, sodium hexafluorosilicate (1400) + TX, sodium pentachlorophenoxide (623) + TX, sodium selenate (IUPAC name) (1401) + TX, sodium thiocyanate [CCN] + TX, sophamide (1402) + TX, spinosad (737) + TX, spiromesifen (739) + TX, spirotetrmat (CCN) + TX, sulcofuron (746) + TX, sulcofuron-sodium (746) + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulphonyl fluoride (756) + TX, sulprofos (1408) + TX, tar oils (alternative name) (758) + TX, tau-fluvalinate (398) + TX, tazimcarb (1412) + TX, TDE (1414) + TX, tebufenozide (762) + TX, tebufenpyrad (763) + TX, tebupirimfos (764) + TX, teflubenzuron (768) + TX, tefluthrin (769) + TX, temephos (770) + TX, TEPP (1417) + TX, terallethrin (1418) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachloroethane [CCN] + TX, tetrachlorvinphos (777) + TX, tetramethrin (787) + TX, theta-cypermethrin (204) + TX, thiacloprid (791) + TX, thiafenox (alternative name) + TX, thiamethoxam (792) + TX, thicrofos (1428) + TX, thiocarboxime (1431) + TX, thiocyclam (798) + TX, thiocyclam hydrogen oxalate (798) + TX, thiodicarb (799) + TX, thiofanox (800) + TX, thiometon (801 ) + TX, thionazin (1434) + TX, thiosultap (803) + TX, thiosultap-sodium (803) + TX, thuringiensin (alternative name) [CCN] + TX, tolfenpyrad (809) + TX, tralomethrin (812) + TX, transfluthrin (813) + TX, transpermethrin (1440) + TX, triamiphos (1441) + TX, triazamate (818) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trichlormetaphos-3 (alternative name) [CCN] + TX, trichloronat (1452) + TX, trifenofos (1455) + TX, triflumuron (835) + TX, trimethacarb (840) + TX, triprene (1459) + TX, vamidothion (847) + TX, vaniliprole [CCN] + TX, veratridine (alternative name) (725) + TX, veratrine (alternative name) (725) + TX, XMC (853) + TX, xylylcarb (854) + TX, YI-5302 (compound code) + TX, zeta-cypermethrin (205) + TX, zetamethrin (alternative name) + TX, zinc phosphide (640) + TX, zolaprofos (1469) and ZXI 8901 (development code) (858) + TX, cyantraniliprole [736994-63-19] + TX, chlorantraniliprole [500008-45-7] + TX, cyenopyrafen [560121-52-0] + TX, cyflumetofen [400882-07-7] + TX,
pyrifluquinazon [337458-27-2] + TX, spinetoram [187166-40-1 + 187166-15-0] + TX, spirotetramat [203313-25-1] + TX, sulfoxaflor [946578-00-3] + TX, flufiprole [704886-18-0] + TX, meperfluthrin [915288-13-0] + TX, tetramethylfluthrin [84937- 88-2] + TX, a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium
pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, trifenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, pyriprole [394730-71-3] + TX,
a nematicide selected from the group of substances consisting of AKD-3088
(compound code) + TX, l,2-dibromo-3-chloropropane (IUPAC/Chemical Abstracts name) (1045) + TX, 1,2-dichloropropane (IUPAC/ Chemical Abstracts name) (1062) + TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063) + TX, 1,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1, 1-dioxide (IUPAC/Chemical Abstracts name) (1065) + TX, 3-(4-chlorophenyl)-5- methylrhodanine (IUPAC name) (980) + TX, 5-methyl-6-thioxo-l,3,5-thiadiazinan-3- ylacetic acid (IUPAC name) (1286) + TX, 6-isopentenylaminopurine (alternative name) (210) + TX, abamectin (1) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, AZ 60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cloethocarb (999) + TX, cytokinins (alternative name) (210) + TX, dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, diamidafos (1044) + TX, dichlofenthion (1051) + TX, dicliphos (alternative name) + TX, dimethoate (262) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ethoprophos (312) + TX, ethylene dibromide (316) + TX, fenamiphos (326) + TX, fenpyrad (alternative name) + TX, fensulfothion ( 1158) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furfural (alternative name) [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (IUPAC name) (542) + TX, isamidofos (1230) + TX, isazofos (1231) + TX, ivermectin (alternative name) [CCN] + TX, kinetin (alternative name) (210) + TX, mecarphon (1258) + TX, metam (519) + TX, metam-potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, Myrothecium verrucaria composition (alternative name) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidon (639) + TX, phosphocarb [CCN] + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachlorothiophene (IUPAC/ Chemical Abstracts name) (1422) + TX, thiafenox (alternative name) + TX, thionazin (1434) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, xylenols [CCN] + TX, YI-5302 (compound code) and zeatin (alternative name) (210) + TX, fluensulfone [318290-98-1] + TX,
a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,
a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-^-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX,
a rodenticide selected from the group of substances consisting of 2-isovalerylindan- 1,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (1005) + TX, coumatetralyl (175) + TX, crimidine (1009) + TX, difenacoum (246) + TX, difethialone (249) + TX, diphacinone (273) + TX, ergocalciferol (301) + TX, flocoumafen (357) + TX, fluoroacetamide (379) + TX, flupropadine (1183) + TX, flupropadine hydrochloride (1183) + TX, gamma-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (IUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (IUPAC name) (640) + TX, methyl bromide (537) + TX, norbormide (1318) + TX, phosacetim (1336) + TX, phosphine (IUPAC name) (640) + TX, phosphorus [CCN] + TX, pindone (1341) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371) + TX, scilliroside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoroacetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851) and zinc phosphide (640) + TX, a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)- ethyl piperonylate (IUPAC name) (934) + TX, 5-(l,3-benzodioxol-5-yl)-3- hexylcyclohex-2-enone (IUPAC name) (903) + TX, farnesol with nerolidol
(alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX,
an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX,
a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX,
a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX,
and biologically active compounds selected from the group consisting of azaconazole (60207-31-0] + TX, bitertanol [70585-36-3] + TX, bromuconazole [116255-48-2] + TX, cyproconazole [94361-06-5] + TX, difenoconazole [119446-68-3] + TX, diniconazole [83657-24-3] + TX, epoxiconazole [106325-08-0] + TX, fenbuconazole [114369-43-6] + TX, fluquinconazole [136426-54-5] + TX, flusilazole [85509-19-9] + TX, flutriafol [76674-21-0] + TX, hexaconazole [79983-71-4] + TX, imazalil
[35554-44-0] + TX, imibenconazole [86598-92-7] + TX, ipconazole [125225-28-7] + TX, metconazole [125116-23-6] + TX, myclobutanil [88671-89-0] + TX, pefurazoate [101903-30-4] + TX, penconazole [66246-88-6] + TX, prothioconazole [178928-70- 6] + TX, pyrifenox [88283-41-4] + TX, prochloraz [67747-09-5] + TX, propiconazole [60207-90-1] + TX, simeconazole [149508-90-7] + TX, tebuconazole [107534-96-3] + TX, tetraconazole [112281-77-3] + TX, triadimefon [43121-43-3] + TX, triadime- nol [55219-65-3] + TX, triflumizole [99387-89-0] + TX, triticonazole [131983-72-7] + TX, ancymidol [12771-68-5] + TX, fenarimol [60168-88-9] + TX, nuarimol
[63284-71-9] + TX, bupirimate [41483-43-6] + TX, dimethirimol [5221-53-4] + TX, ethirimol [23947-60-6] + TX, dodemorph [1593-77-7] + TX, fenpropidine [67306-00- 7] + TX, fenpropimorph [67564-91-4] + TX, spiroxamine [118134-30-8] + TX, tridemorph [81412-43-3] + TX, cyprodinil [121552-61-2] + TX, mepanipyrim
[110235-47-7] + TX, pyrimethanil [53112-28-0] + TX, fenpiclonil [74738-17-3] + TX, fludioxonil [131341-86-1] + TX, benalaxyl [71626-11-4] + TX, furalaxyl
[57646-30-7] + TX, metalaxyl [57837-19-1] + TX, R-metalaxyl [70630-17-0] + TX, ofurace [58810-48-3] + TX, oxadixyl [77732-09-3] + TX, benomyl [17804-35-2] + TX, carbendazim [10605-21-7] + TX, debacarb [62732-91-6] + TX, fuberidazole [3878-19-1] + TX, thiabendazole [148-79-8] + TX, chlozolinate [84332-86-5] + TX, dichlozoline [24201-58-9] + TX, iprodione [36734-19-7] + TX, myclozoline [54864- 61-8] + TX, procymidone [32809-16-8] + TX, vinclozoline [50471-44-8] + TX, boscalid [188425-85-6] + TX, carboxin [5234-68-4] + TX, fenfuram [24691-80-3] + TX, flutolanil [66332-96-5] + TX, mepronil [55814-41-0] + TX, oxycarboxin [5259- 88-1] + TX, penthiopyrad [183675-82-3] + TX, thifluzamide [130000-40-7] + TX, guazatine [108173-90-6] + TX, dodine [2439-10-3] [112-65-2] (free base) + TX, iminoctadine [13516-27-3] + TX, azoxystrobin [131860-33-8] + TX, dimoxystrobin [149961-52-4] + TX, enestrobunn {Proc. BCPC, Int. Congr., Glasgow, 2003, 1, 93 } + TX, fluoxastrobin [361377-29-9] + TX, kresoxim-methyl [143390-89-0] + TX, metominostrobin [133408-50-1] + TX, trifloxystrobin [141517-21-7] + TX, orysastrobin [248593-16-0] + TX, picoxystrobin [117428-22-5] + TX, pyraclostrobin [175013-18-0] + TX, ferbam [14484-64-1] + TX, mancozeb [8018-01-7] + TX, maneb [12427-38-2] + TX, metiram [9006-42-2] + TX, propineb [12071-83-9] + TX, thiram [137-26-8] + TX, zineb [12122-67-7] + TX, ziram [137-30-4] + TX, captafol [2425-06-1] + TX, captan [133-06-2] + TX, dichlofluanid [1085-98-9] + TX, fluoroimide [41205-21-4] + TX, folpet [133-07-3 ] + TX, tolylfluanid [731-27-1] + TX, bordeaux mixture [8011-63-0] + TX, copperhydroxid [20427-59-2] + TX, copperoxychlorid [1332-40-7] + TX, coppersulfat [7758-98-7] + TX, copperoxid [1317-39-1] + TX, mancopper [53988-93-5] + TX, oxine-copper [10380-28-6] + TX, dinocap [131-72-6] + TX, nitrothal-isopropyl [10552-74-6] + TX, edifenphos [17109- 49-8] + TX, iprobenphos [26087-47-8] + TX, isoprothiolane [50512-35-1] + TX, phosdiphen [36519-00-3] + TX, pyrazophos [13457-18-6] + TX, tolclofos-methyl [57018-04-9] + TX, acibenzolar-S-methyl [135158-54-2] + TX, anilazine [101-05-3] + TX, benthiavalicarb [413615-35-7] + TX, blasticidin-S [2079-00-7] + TX, chinomethionat [2439-01-2] + TX, chloroneb [2675-77-6] + TX, chlorothalonil
[1897-45-6] + TX, cyflufenamid [180409-60-3] + TX, cymoxanil [57966-95-7] + TX, dichlone [117-80-6] + TX, diclocymet [139920-32-4] + TX, diclomezine
[62865-36-5] + TX, dicloran [99-30-9] + TX, diethofencarb [87130-20-9] + TX, dimethomorph [110488-70-5] + TX, SYP-LI90 (Flumorph) [211867-47-9] + TX, dithianon [3347-22-6] + TX, ethaboxam [162650-77-3] + TX, etridiazole [2593-15- 9] + TX, famoxadone [131807-57-3] + TX, fenamidone [161326-34-7] + TX, fenoxanil [115852-48-7] + TX, fentin [668-34-8] + TX, ferimzone [89269-64-7] + TX, fluazinam [79622-59-6] + TX, fluopicolide [239110-15-7] + TX, flusulfamide
[106917-52-6] + TX, fenhexamid [126833-17-8] + TX, fosetyl-aluminium [39148-24- 8] + TX, hymexazol [10004-44-1] + TX, iprovalicarb [140923-17-7] + TX, IKF-916 (Cyazofamid) [120116-88-3] + TX, kasugamycin [6980-18-3] + TX, methasulfocarb [66952-49-6] + TX, metrafenone [220899-03-6] + TX, pencycuron [66063-05-6] + TX, phthalide [27355-22-2] + TX, polyoxins [11113-80-7] + TX, probenazole
[27605-76-1] + TX, propamocarb [25606-41-1] + TX, proquinazid [189278-12-4] + TX, pyroquilon [57369-32-1] + TX, quinoxyfen [124495-18-7] + TX, quintozene [82- 68-8] + TX, sulphur [7704-34-9] + TX, tiadinil [223580-51-6] + TX, triazoxide
[72459-58-6] + TX, tricyclazole [41814-78-2] + TX, triforine [26644-46-2] + TX, validamycin [37248-47-8] + TX, zoxamide (RH7281) [156052-68-5] + TX, mandipropamid [374726-62-2] + TX, isopyrazam [881685-58-1] + TX, sedaxane [874967-67-6] + TX, 3 -difluorom ethyl- 1 -methyl- lH-pyrazole-4-carboxylic acid (9- dichloromethylene-l,2,3,4-tetrahydro-l,4-methano-naphthalen-5-yl)-amide (dislosed in WO 2007/048556) + TX, 3-difluoromethyl-l-methyl-lH-pyrazole-4-carboxylic acid [2-(2,4-dichlorophenyl)-2-methoxy-l-methyl-ethyl]-amide (disclosed in WO 2008/148570) + TX, l-[4-[4-[(5S)5-(2,6-difluorophenyl)-4,5-dihydro-l,2-oxazol-3- yl]-l,3-thiazol-2-yl]piperidin-l-yl]-2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l- yl]ethanone + TX, l-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-l,2-oxazol-3-yl]-l,3- thiazol-2-yl]piperidin- 1 -yl] -2- [5 -methyl-3 -(trifluoromethyl)- 1 H-pyrazol- 1 - yljethanone [1003318-67-9], both disclosed in WO 2010/123791, WO 2008/013925, WO 2008/013622 and WO 2011/051243 page 20) +TX, S)-[3-(4-Chloro-2-fluoro- phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y l]-pyridin-3-yl-methanol + TX, 3-(4- Chloro-2-fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y l]-pyridin-3-yl- methanol + TX, 3-difluoromethyl-l-methyl-lH-pyrazole-4-carboxylic acid (3',4',5'- trifluoro-biphenyl-2-yl)-amide (disclosed in WO 2006/087343) + TX, 3- (difluoromethyl)-N-methoxy- 1 -methyl-N-[ 1 -methyl-2-(2,4,6-trichlorophenyl)ethyl]- lH-Pyrazole-4-carboxamide + TX, 4-[(55)-5-(3,5-dichlorophenyl)-5-
(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzamide + TX, 4- [(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N- (thietan-3-yl)benzamide + TX, 4-[(5,S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)- 4H-isoxazol-3-yl]-2-methyl-N-(cis-l-oxo-thietan-3-yl)benzamide + TX, 4-[(5R)-5- (3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(cis-l-oxo- thietan-3-yl)benzamide + TX, 4-[(5,S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H- isoxazol-3-yl]-2-methyl-N-(trans-l-oxo-thietan-3-yl)benzamide
4-[(5R)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N- (trans-l-oxo-thietan-3-yl)benzamide + TX, 4-[(5(S)-5-(3,5-dichlorophenyl)-5- (trifluoromethyl)-4H-isoxazol-3-yl]-N-(l, l-dioxothietan-3-yl)-2-methyl-benzamide + TX, 4- [(5R)-5 -(3 , 5 -dichlorophenyl)-5 -(trifluoromethyl)-4H-i soxazol-3 -yl] -N-( 1 , 1 - dioxothietan-3-yl)-2-methyl-benzamide + TX, 4-[(5,S)-5-(3,5-dichlorophenyl)-5- (trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2- trifluoroethylamino)ethyl]benzamide + TX, 4-[(5R)-5-(3,5-dichlorophenyl)-5- (trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2- trifluoroethylamino)ethyl]benzamide + TX.
The components (B) are known. The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound "abamectin" is described under entry number (1). Where "[CCN]" is added hereinabove to the particular compound, the compound in question is included in the "Compendium of Pesticide Common Names", which is accessible on the internet [A. Wood; Compendium of Pesticide Common Names, Copyright © 1995-2004]; for example, the compound "acetoprole" is described under the internet address http://www.alanwood.net/pesticides/ or preferably one of the further pesticides listed below. It has been found that the use of component (B) in combination with component TX surprisingly and substantially may enhance the effectiveness of the latter against fungi, and vice versa. Additionally, the method of the invention is effective against a wider spectrum of such fungi that can be combated with the active ingredients of this method, when used solely.
In general, the weight ratio of component TX to component (B) is from 2000 : 1 to 1 : 1000. A non-limiting example for such weight ratios is compound of formula I :
compound of formula B (component (B)) is 10: 1. The weight ratio of component TX to component (B) is preferably from 100 : 1 to 1 : 100; more preferably from 20 : 1 to 1 : 50.
The active ingredient mixture of component TX to component (B) comprises compounds of formula I and a further, other biocidally active ingredients or compositions or if desired, a solid or liquid adjuvant preferably in a mixing ratio of from 1000: 1 to 1 : 1000, especially from 50: 1 to 1 :50, more especially in a ratio of from 20: 1 to 1 :20, even more especially from 10: 1 to 1 : 10, very especially from 5: 1 and 1 :5, special preference being given to a ratio of from 2: 1 to 1 :2, and a ratio of from 4: 1 to 2: 1 being likewise preferred, above all in a ratio of 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.
It has been found, surprisingly, that certain weight ratios of component TX to component (B) are able to give rise to synergistic activity. Therefore, a further aspect of the invention are compositions, wherein component TX and component (B) are present in the composition in amounts producing a synergistic effect. This synergistic activity is apparent from the fact that the fungicidal activity of the composition comprising component TX and component (B) is greater than the sum of the fungicidal activities of component TX and of component (B). This synergistic activity extends the range of action of component TX and component (B) in two ways. Firstly, the rates of application of component TX and component (B) are lowered whilst the action remains equally good, meaning that the active ingredient mixture still achieves a high degree of phytopathogen control even where the two individual components have become totally ineffective in such a low application rate range. Secondly, there is a substantial broadening of the spectrum of phytopathogens that can be controlled.
A synergistic effect exists whenever the action of an active ingredient combination is greater than the sum of the actions of the individual components. The action to be expected E for a given active ingredient combination obeys the so-called COLBY formula and can be calculated as follows (COLBY, S.R. "Calculating synergistic and antagonistic responses of herbicide combination". Weeds, Vol. 15, pages 20-22;
1967):
ppm = milligrams of active ingredient (= a.i.) per liter of spray mixture
X = % action by active ingredient A) using p ppm of active ingredient
Y = % action by active ingredient B) using q ppm of active ingredient.
According to COLBY, the expected (additive) action of active ingredients A)+B)
X · Y
using p+q ppm of active ingredient is E = X + Y -
If the action actually observed (O) is greater than the expected action (E), then the action of the combination is super-additive, i.e. there is a synergistic effect. In mathematical terms, synergism corresponds to a positive value for the difference of (O-E). In the case of purely complementary addition of activities (expected activity), said difference (O-E) is zero. A negative value of said difference (O-E) signals a loss of activity compared to the expected activity. However, besides the actual synergistic action with respect to fungicidal activity, the compositions according to the invention can also have further surprising advantageous properties. Examples of such advantageous properties that may be mentioned are: more advantageuos degradability; improved toxicological and/or ecotoxicological behaviour; or improved characteristics of the useful plants including: emergence, crop yields, more developed root system, tillering increase, increase in plant height, bigger leaf blade, less dead basal leaves, stronger tillers, greener leaf colour, less fertilizers needed, less seeds needed, more productive tillers, earlier flowering, early grain maturity, less plant verse (lodging), increased shoot growth, improved plant vigor, and early germination.
Some compositions according to the invention have a systemic action and can be used as foliar, soil and seed treatment fungicides.
With the compositions according to the invention it is possible to inhibit or destroy the phytopathogenic microorganisms which occur in plants or in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different useful plants, while at the same time the parts of plants which grow later are also protected from attack by
phytopathogenic microorganisms. The compositions according to the invention can be applied to the phytopathogenic microorganisms, the useful plants, the locus thereof, the propagation material thereof, storage goods or technical materials threatened by microorganism attack.
The compositions according to the invention may be applied before or after infection of the useful plants, the propagation material thereof, storage goods or technical materials by the microorganisms. A further aspect of the present invention is a method of controlling diseases on useful plants or on propagation material thereof caused by phytopathogens, which comprises applying to the useful plants, the locus thereof or propagation material thereof a composition according to the invention. Preferred is a method, which comprises applying to the useful plants or to the locus thereof a composition according to the invention, more preferably to the useful plants. Further preferred is a method, which comprises applying to the propagation material of the useful plants a composition according to the invention. Throughout this document the expression "composition" stands for the various mixtures or combinations of components TX and (B), for example in a single "ready- mix" form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix", and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the components TX and (B) is not essential for working the present invention.
The compositions according to the invention may also comprise more than one of the active components (B), if, for example, a broadening of the spectrum of disease control is desired. For instance, it may be advantageous in the agricultural practice to combine two or three components (B) with component TX. An example is a composition comprising a compound of formula (I), azoxystrobin and cyproconazole. Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from lOg to 1kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as seed drenching agent, convenient rates of application are from lOmg to lg of active substance per kg of seeds. The rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits. The compounds of formula (I), or a pharmaceutical salt thereof, described above may also have an advantageous spectrum of activity for the treatment and/or prevention of microbial infection in an animal. "Animal" can be any animal, for example, insect, mammal, reptile, fish, amphibian, preferably mammal, most preferably human.
"Treatment" means the use on an animal which has microbial infection in order to reduce or slow or stop the increase or spread of the infection, or to reduce the infection or to cure the infection. "Prevention" means the use on an animal which has no apparent signs of microbial infection in order to prevent any future infection, or to reduce or slow the increase or spread of any future infection.
According to the present invention there is provided the use of a compound of formula (I) in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal. There is also provided the use of a compound of formula (I) as a pharmaceutical agent. There is also provided the use of a compound of formula (I) as an antimicrobial agent in the treatment of an animal. According to the present invention there is also provided a pharmaceutical
composition comprising as an active ingredient a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. This composition can be used for the treatment and/or prevention of antimicrobial infection in an animal. This pharmaceutical composition can be in a form suitable for oral administration, such as tablet, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions dispersible powders, dispersible granules, syrups and elixirs. Alternatively this pharmaceutical composition can be in a form suitable for topical application, such as a spray, a cream or lotion. Alternatively this pharmaceutical composition can be in a form suitable for parenteral administration, for example injection. Alternatively this pharmaceutical composition can be in inhalable form, such as an aerosol spray.
The compounds of formula (I) may be effective against various microbial species able to cause a microbial infection in an animal. Examples of such microbial species are those causing Aspergillosis such as Aspergillus fumigatus, A. flavus, A. terms, A. nidulans and niger, those causing Blastomycosis such as Blastomyces dermatitidis; those causing Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and C. lusitaniae; those causing Coccidioidomycosis such as Coccidioides immitis; those causing Cryptococcosis such as Cryptococcus
neoformans; those causing Histoplasmosis such as Histoplasma capsulatum and those causing Zygomycosis such as Absidia corymbifera, Rhizomucor pusillus and Rhizopus arrhizus. Further examples are Fusarium Spp such as Fusarium oxysporum and Fusarium solani and Scedosporium Spp such as Scedosporium apiospermum and Scedosporium prolifwans. Still further examples are Microsporum Spp, Trichophyton Spp, Epidermophyton Spp, Mucor Spp, Sporothorix Spp, Phialophora Spp,
Cladosporium Spp, Petriellidium spp, Paracoccidioides Spp and Histoplasma Spp.
The following non-limiting examples illustrate the above-described invention in greater detail without limiting it.
EXAMPLES
Example 1 : The preparation of 2-(3'-fluoro-[2,4']bipyridinyl-6-yl)-quinazoline (Compound T 1.1.176) a) Preparation of 2-(6-bromopyridin-2-yl)-l,2,3,4-tetrahydroquinazoline A solution of pyridine (5.1 g, 64 mmol) in 50 ml of dichloromethane is added to a solution of thionyl chloride (7.6 g, 64 mmol) in 50 ml of dichloromethane at 0 °C. The mixture is stirred for 15 min at 0 °C, then 6-bromopyridine-2-carboxaldehyde (10 g, 54 mmol) is added slowly at 0 °C. The resulting mixture is stirred for 1 h at room temperature, then a solution of 2-aminobenzylamine (7.2 g, 59 mmol) in 50 ml of dichloromethane is added dropwise. The reaction mixture is stirred for 1 h at room temperature, then diluted with 50 ml of a sodium acetate solution (8.8 g in water), basified with sodium hydroxide solution (2 M in water) and extracted with
dichloromethane. The organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The remainder is purified by chromatography on silica gel, using a mixture of cyclohexane / ethyl acetate 2 : 1 as eluent to obtain 2- (6-bromopyridin-2-yl)-l,2,3,4-tetrahydroquinazoline. 1H- MR (CDC13): δ = 4.02 (d, 1H), 4.27 (d, 1H), 5.01 (bs, 1H), 5.23 (s, 1H), 6.68 - 6.76 (m, 2H), 6.93 (d, 1H), 7.07 (t, 1H), 7.44 (d, 1H), 7.58 - 7.63 (m, 2H). MS: m/z = 291 (M+l). b) Preparation of 2-(6-bromopyridin-2-yl)-quinazoline
2,3-Dichloro-5,6-dicycano-p-benzoquinone (121 g, 0.53 mol) is added to a suspension of 2-(6-bromopyridin-2-yl)-l,2,3,4-tetrahydroquinazoline (77 g, 0.26 mol) in 1450 ml of toluene. The reaction mixture is stirred for 30 min at room temperature, basified with sodium hydroxide solution (5 M in water) and extracted with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The remainder is purified by chromatography on silica gel, using a mixture of cyclohexane / ethyl acetate / dichloromethane 2 : 1 : 1 as eluent to obtain 2-(6-bromopyridin-2-yl)-quinazoline. 1H- MR (CDC13): δ = 7.63 (d, 1H), 7.69 - 7.78 (m, 2H), 7.93 - 8.01 (m, 2H), 8.20 (d, 1H), 8.64 (d, 2H), 9.59 (s, 1H). MS: m/z = 287 (M+l). c) In a sealed tube under argon atmosphere, to a solution of 2-(6-bromopyridin- 2-yl)-quinazoline (150 mg, 0.52 mmol) in dimethoxyethane (8 ml) 3-fluoro-4-pridine boronic acid is added followed by a 3M aq solution of sodium carbonate (0.7 ml). The mixture is degassed for 5 min, then (diphenylphosphinoferrocenyl)palladium dichloride, dicloromethane complex (43 mg, 0.05 mmol) is added. The tube is sealed and the mixture is stirred at 100°C for 16 hours. Subsequently, the mixture is cooled and poured into water, then extracted with ethyl acetate and washed with 2M solution of sodium hydroxyde. The collected organic fractions were washed with a 10% sol of ammonia, with brine, dried over anhydrous sodium sulphate, filtered and evaporated to dryness. The remainder is purified by flash chromatography on silica gel, using a gradient of cyclohexane / ethyl acetate 100 : 1 to 1 : 100 as eluent to obtain 2-(3'- fluoro-[2,4']bipyridinyl-6-yl)-quinazoline (Compound Tl .1.176). 1H- MR (CDC13): δ = 7.72 (t, 1H), 7.94 - 8.08 (m, 4H), 8.20 - 8.30 (m, 2H), 8.55-8.62 (m, 2H), 8.74 (dd, 1H), 9.62 (s, 1H) MS: m/z = 303 (M+l). according to the same procedure, starting from 2-(6-bromo-5-methylpyridin-2-yl)- quinazoline (150 mg, 0.52 mmol) and 2-methoxy- 5 -pyridine boronic acid after purification 2-(6'-methoxy-3-methyl-[2,3']bipyridinyl-6-yl)-quinazoline was obtained (Compound Tl .1.137). 1H- MR (CDC13): δ = 2.50 (s, 3H), 4.02 (s, 3H), 6.89 (d, 1H), 7.65 (t, 1H), 7.80 (d, 1H), 7.91 - 8.02 (m, 3H), 8.20 (d, 1H), 8.47 (d, 1H), 8.55 (d, 1H), 9.61 (s, 1H) MS: m/z = 329 (M+l).
Example 2: This example illustrates the preparation of 2-[6-(6-chloro-pyridin-3- ylmethyl)-pyridin-2-yl]-quinazoline (Compound Tl .1.321)
A solution of 2-(6-bromopyridin-2-yl)-quinazoline (572 mg, 2.0 mmol) in 15 ml of tetrahydrofurane is degassed with argon for 10 min.
Tetrakis(triphenylphosphin)palladium (231 mg, 0.2 mmol) is added and the mixture is stirred for 30 min at 65 °C. 4 ml of a 2-chloro-5-pyridylmethylzinc bromide solution (0.5 M in tetrahydrofurane) are added and the reaction mixture is heated to reflux for 2 h. Subsequently the mixture is cooled and 250 ml of a EDTA solution (12 % in water) are added and the mixture is stirred for further 16 h at room temperature, then diluted with 1 N aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The remainder is purified by chromatography on silica gel, using a mixture of cyclohexane / ethyl acetate 2 : 3 as eluent to obtain 2-[6-(6-chloro- pyridin-3-ylmethyl)-pyridin-2-yl]-quinazoline (Compound Tl .1.321). 1H- MR (CDC13): δ = 4.34 (s, 2H), 7.09 (d, 1H), 7.20 (d, 1H), 7.58 - 7.66 (m, 2H), 7.78 (t, 1H), 7.87 - 7.93 (m, 2H), 8.13 (d, 1H), 8.35 (s, 1H), 8.48 (d, 1H), 9.57 (s, 1H). MS: m/z = 333 (M+l).
Example 3 : This example illustrates the preparation of 2-(6-Pyridin-2-ylethynyl- pyridin-2-yl)-quinazoline (Compound Tl .1.346) A mixture of 2-(6-bromopyridin-2-yl)-quinazoline (200 mg, 0.70 mmol), 2- ethynylpyridine (225 mg, 1.75 mmol) and diisopropylamine (141 mg, 1.40 mmol) in dimethylformamide (4 ml) is degassed with argon for 5 min. Copper(I) iodide (13 mg, 0.07 mmol) and bis(triphenylphosphine)palladiumdichloride are added to the mixture. The vial is sealed and heated under microwave conditions at 160°C. Subsequently the mixture is cooled and a EDTA solution (12 % in water) are added and the mixture is stirred for further 16 h at room temperature, then diluted with 1 N aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The remainder is purified by flash chromatography on silica gelusing a gradient of cyclohexane / ethyl acetate 100 : 1 to 1 : 100 as eluent to obtain 2-(6-Pyridin-2- ylethynyl-pyridin-2-yl)-quinazoline (Compound Tl .1.346). 1H- MR (CDC13): δ = 7.28-7.32 (m, 2H), 7.65 - 7.75 (m, 2H), 7.79 (d, 1H), 7.90 - 8.04 (m, 3H), 8.24 (d, 1H), 8.65 (d, 1H), 8.69 (d, 1H), 9.56 (s, 1H). MS: m/z = 309 (M+l).
Example 4: This example illustrates the preparation of 2-[6-(pyridin-2-yloxy)-pyridin- 2-yl]-quinazoline (Compound Tl .1.376)
To a mixture of 2-(6-bromopyridin-2-yl)-quinazoline (200 mg, 0.70 mmol), 2- hydroxypyridine (83 mg, 0.70 mmol), copper(I) bromide (20 mg, 0.14 mmol) and cesium carbonate (570 mg, 1.75 mmol) in degassed dimethylformamide (2 ml)
2,2,6,6-tetramethyl-3,5-heptandion (103 mg, 0.56 mmol) was added under argon, at room temperature. The vial was sealed and stirred at 135°C during 2 hours.
Subsequently, the mixture is cooled and poured into water, then extracted with ethyl acetate and washed with 1M solution of sodium hydroxyde. The collected organic fractions were washed with brine, dried over anhydrous sodium sulphate, filtered and evaporated to dryness. The remainder is purified by flah chromatography on silica gel, using a gradient of cyclohexane / ethyl acetate 100 : 1 to 1 : 100 as eluent to obtain 2- [6-(pyridin-2-yloxy)-pyridin-2-yl]-quinazoline (Compound Tl .1.376). 1H- MR (CDC13): δ = 7.05 (dd, 1H), 7.15 (d, 1H), 7.28 (d, 1H), 7.67 (t, 1H), 7.74 (m, 1H), 7.90-8.02 (m, 3H), 8.18-8.23 (m, 2H), 8.57 (d, 1H), 9.58 (s, 1H) MS: m/z = 301 (M+l). Example 5 : This example illustrates the preparation of 2-[6-(4-methyl-pyrimidin-2- ylsulfanyl)-pyridin-2-yl]-quinazoline (Compound Tl .1.476) A mixture of 2-(6-bromopyridin-2-yl)-quinazoline (200 mg, 0.7 mmol), 2- mercapto-4-methylpyrimidine (125 mg, 0.77 mmol) and potassium carbonate (245 mg, 1.8 mmol) in 10 ml of Ν,Ν-dimethylformamide is heated unter argon for 8 h at 110 °C. Subsequently the mixture is cooled, diluted with brine and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and evaporated under reduced pressure. The remainder is purified by chromatography on silica gel, using a mixture of cyclohexane / ethyl acetate 1 : 1 as eluent to obtain 2-[6-(4-methyl- pyrimidin-2-ylsulfanyl)-pyridin-2-yl]-quinazoline (Compound Tl .1.476). 1H- MR (CDC13): δ = 2.47 (s, 3H), 6.88 (d, 1H), 7.69 (t, 2H), 7.91 - 8.04 (m, 4H), 8.20 (d, 1H), 8.36 (s, 1H), 8.65 (d, 1H), 9.58 (s, 1H). MS: m/z = 332 (M+l).
Table A below defines chemical designations for the substituents Ri, R2 and R3 for the compounds of formula I:
Figure imgf000060_0001
Table A: chemical designations for substituents A, R1 and R2 of the compound of formula I:
Line A R1 R2
Figure imgf000060_0002
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Line A R1 R2
Figure imgf000064_0001
Figure imgf000065_0001
Figure imgf000066_0001
Figure imgf000067_0001
Figure imgf000068_0001
Figure imgf000069_0001
Line A R1 R2
Figure imgf000070_0001
Figure imgf000071_0001
Line A R1 R2
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000075_0001
Figure imgf000076_0001
Line A R1 R2
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
Figure imgf000083_0001
Figure imgf000084_0001
Figure imgf000085_0001
Line A R1 R2
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
Figure imgf000089_0001
Line A R1 R2
Figure imgf000090_0001
Figure imgf000091_0001
Line A R1 R2
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Line A R1 R2
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
Table 1: This table discloses the 500 compounds T 1.1.1 to T 1.1.500 of formula
Figure imgf000105_0001
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A. l . 500 of Table A. For example, the specific compound Tl .1.23 is the compound of the formula Tl, in which each of the of the variables A, R1 and R2 has the specific meaning given in the line A.1.23 of the Table A and the compound Tl .1.23
has therefore the following Formula:
Figure imgf000105_0002
According to the same system, also all of the other 500 specific compounds disclosed in the Table 1 as well as all of the specific compounds disclosed in the Tables 2 to 11 are specified analogously.
Table 2: This table discloses the 500 compounds T2.1.1 to T2.1.500 of the formula
(T2),
Figure imgf000105_0003
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A. Table 3 : This table disc .500 of the formula
Figure imgf000106_0001
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
Table 4: This table discl T4.1.500 of the formula
Figure imgf000106_0002
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
Table 5 : This table discloses the 500 compounds T5.1.1 to T5.1.500 of the formula
Figure imgf000107_0001
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
Table 6: This table of the formula
Figure imgf000107_0002
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
Table 7: This table discloses the 500 compounds T7.1.1 to T7.1.500 of the formula
Figure imgf000107_0003
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A. Table 8: This table discloses the 500 compounds T8.1.1 to T8.1.500 of the formula
Figure imgf000108_0001
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
Table 9: This table discloses the 500 compounds T9.1.1 to T9.1.500 of the formula
Figure imgf000108_0002
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
Table 10: This table discloses the 500 compounds TIO.1.1 to T10.1.500 of the formula
Figure imgf000108_0003
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A. Table 11 : This table discloses the 500 compounds Ti l .1.1 to Ti l .1.500 of the formula
Figure imgf000109_0001
in which, for each of these 500 specific compounds, each of the of the variables A, R1 and R2 has the specific meaning given in the corresponding line, appropriately selected from the 500 lines A.1.1 to A.1.500 of the Table A.
Table 12 shows selected m.p. data and selected LC/MS data for compounds of Tables 1 to 11. Throughout this description, temperatures are given in degrees Celsius and "m.p." means melting point. LC/MS means Liquid Chromatography Mass
Spectroscopy and the description of the apparatus and the method is: (HP 1100 HPLC from Agilent, Phenomenex Gemini CI 8, 3 μπι (= 3 micro meter) particle size, 110 Angstrom, 30 x 3 mm column, 1.7mL/min., 60 °C, H20 + 0.05% HCOOH (95%) / CH3CN/MeOH 4: 1 + 0.04% HCOOH (5%) - 2 min. - CH3CN/MeOH 4: 1 + 0.04% HCOOH (5%) - 0.8 min., ZQ Mass Spectrometer from Waters, ionization method: electrospray (ESI), Polarity: positive ions, Capillary (kV) 3.00, Cone (V) 30.00, Extractor (V) 2.00, Source Temperature (°C) 100, Desolvation Temperature (°C) 250, Cone Gas Flow (L/Hr) 50, Desolvation Gas Flow (L/Hr) 400)). Table 12: Melting point and LC/MS data for compounds of Tables 1 to 11 :
Compound No. Melting point (°C) LC MS
Tl .1.7 Rt=0.73 min; MS: m/z=288.27 (M+l)
Tl .1.9 Rt=1.37 min; MS: m/z=304.31 (M+l)
Tl .1.11 Rt=0.74 min; MS: m/z=316.19 (M+l)
Tl .1.16 Rt=0.97 min; MS: m/z=323.65 (M+l)
Tl .1.17 Rt=1.01 min; MS: m/z=338.26 (M+l) Compound No. Melting point (°C) LCMS
Tl.1.22 Rt=0.88 min; MS: m/z=304.25 (M+1)
Tl.1.26 Rt=1.29 min; MS: m/z=290.1 (M+1)
Tl.1.29 Rt=1.48 min; MS: m/z=320.27 (M+1)
Tl.1.31 Rt=0.78 min; MS: m/z=318.15 (M+1)
Tl.1.32 Rt=0.78 min; MS: m/z=332.22 (M+1)
Tl.1.36 Rt=0.77 min; MS: m/z=318.13 (M+1)
Tl.1.37 Rt=0.75 min; MS: m/z=332.19 (M+1)
Tl.1.42 Rt=0.84 min; MS: m/z=346.23 (M+1)
Tl.1.49 Rt=1.5 min; MS: m/z=334.31 (M+1)
Tl.1.54 Rt=1.54 min; MS: m/z=334.3 (M+1)
Tl.1.56 Rt=1.01 min; MS: m/z=340.16 (M+1)
Tl.1.57 Rt=1.08 min; MS: m/z=354.23 (M+1)
Tl.1.61 Rt=1.03 min; MS: m/z=340.14 (M+1)
Tl.1.66 Rt=0.45 min; MS: m/z=282.22 (M+1)
Tl.1.67 Rt=0.48 min; MS: m/z=302.29 (M+1)
Tl.1.71 Rt=0.64 min; MS: m/z=360.2 (M+1)
Tl.1.72 Rt=0.73 min; MS: m/z=388.32 (M+1)
Tl.1.84 Rt=1.18 min; MS: m/z=340.32 (M+1)
Tl.1.87 Rt=0.75 min; MS: m/z=324.27 (M+1)
Tl.1.101 Rt=0.77 min; MS: m/z=285.16 (M+1)
Tl.1.104 Rt=0.85 min; MS: m/z=315.3 (M+1)
Tl.1.107 Rt=0.79 min; MS: m/z=333.23 (M+1)
Tl.1.109 Rt=1.44 min; MS: m/z=349.29 (M+1)
Tl.1.114 Rt=1.46 min; MS: m/z=361.31 (M+1)
Tl.1.119 Rt=1.54 min; MS: m/z=363.3 (M+1)
Tl.1.121 Rt=1.08 min; MS: m/z=315.28 (M+1)
Tl.1.122 Rt=1.34 min; MS: m/z=329.11 (M+1)
Tl.1.124 Rt=1.25 min; MS: m/z=345.33 (M+1)
Tl.1.126 Rt=1.16 min; MS: m/z=319.06 (M+1)
Tl.1.127 Rt=1.39 min; MS: m/z=333.07 (M+1) Compound No. Melting point (°C) LCMS
Tl.1.131 Rt=1.15 min; MS: m/z=345.46 (M+1)
Tl.1.132 Rt=1.46 min; MS: m/z=359.1 (M+1)
Tl.1.136 Rt=1.21 min; MS: m/z=315.12 (M+1)
Tl.1.137 Rt=1.39 min; MS: m/z=329.11 (M+1)
Tl.1.139 Rt=1.37 min; MS: m/z=345.36 (M+1)
Tl.1.142 Rt=0.79 min; MS: m/z=333.23 (M+1)
Tl.1.144 Rt=1.44 min; MS: m/z=349.27 (M+1)
Tl.1.154 Rt=1.24 min; MS: m/z=333.3 (M+1)
Tl.1.159 Rt=1.22 min; MS: m/z=365.33 (M+1)
Tl.1.161 Rt=0.9 min; MS: m/z=369.17 (M+1)
Tl.1.162 Rt=0.93 min; MS: m/z=383.24 (M+1)
Tl.1.167 Rt=0.27 min; MS: m/z=299.29 (M+1)
Tl.1.169 Rt=0.85 min; MS: m/z=315.3 (M+1)
Tl.1.172 Rt=0.74 min; MS: m/z=317.27 (M+1)
Tl.1.176 145 - 150 °C
Tl.1.179 Rt=1.21 min; MS: m/z=333.3 (M+1)
Tl.1.184 Rt=1.45 min; MS: m/z=349.28 (M+1)
Tl.1.189 Rt=0.87 min; MS: m/z=329.34 (M+1)
Tl.1.192 Rt=0.49 min; MS: m/z=300.27 (M+1)
Tl.1.196 Rt=0.82 min; MS: m/z=380.15 (M+1)
Tl.1.204 Rt=1.45 min; MS: m/z=362.32 (M+1)
Tl.1.244 Rt=1.38 min; MS: m/z=368.35 (M+1)
Tl.1.249 Rt=1.59 min; MS: m/z=356.32 (M+1)
Tl.1.256 Rt=1.13 min; MS: m/z=374.19 (M+1)
Tl.1.257 Rt=1.09 min; MS: m/z=388.27 (M+1)
Tl.1.261 Rt=1.19 min; MS: m/z=390.19 (M+1)
Tl.1.262 Rt=1.16 min; MS: m/z=404.28 (M+1)
Tl.1.266 Rt=0.89 min; MS: m/z=335.11 (M+1)
Tl.1.267 Rt=1.06 min; MS: m/z=349.1 (M+1)
Tl.1.269 Rt=1.19 min; MS: m/z=365.45 (M+1) Compound No. Melting point (°C) LC MS
Tl.1.274 Rt=1.03 min; MS: m/z=365.35 (M+l)
Tl.1.284 Rt=0.94 min; MS: m/z=365.35 (M+l)
Tl.1.286 Rt=1.82 min; MS: m/z=346.31 (M+l)
Tl.1.322 171 - 174 °C
Tl.l . 326 Rt=1.58 min; MS: m/z=329 (M+l)
Tl.1.346 68 - 71 °C
Tl.1.347 Rt=1.36 min; MS: m/z=323.18 (M+l)
Tl.1.371 162 - 163 °C
Tl.1.376 141 - 142 °C
Tl.1.432 157 - 159 °C
T.l.1.441 143 - 146 °C
Tl.1.446 170 - 172 °C
Tl.1.472 174 - 177 °C
Tl.1.476 133 - 134 °C
Tl.1.477 138 - 140 °C
T3.1.137 133 - 137 °C
Table 13: Melting point and LC/MS data for further compounds
Figure imgf000112_0001
Formulation examples for compounds of formula I: Example F-2.1 to F-2.2: Emulsifiable concentrates
Components F-2.1 F-2.2 Compound of Tables 1-11 25% 50%
calciumdodecylbenzenesulfonate 5% 6%
castoroilpolyethyleneglycolether
(36mol ethyl enoxyunits) 5% - tributylphenolpolyethyleneglycolether
(3 Omol ethyl enoxyunits) -
- 20%
xylenemixture 65% 20%
Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
Example F-2: Emulsifiable concentrate
Figure imgf000113_0001
Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
Examples F-3.1 to F-3.4: Solutions
Components F- F- F- F-
3.1 3.2 3.3 3.4
Compound of Tables 1-11 80% 10% 5% 95% propylene glycol monomethyl ether 20% - - - polyethylene glycol - 70% - -
(relative molecular mass: 400 atomic mass units) N-methylpyrrolid-2-one - 20% - - epoxidised coconut oil - - 1% 5% benzin (boiling range: 160-190°) - - 94% -
The solutions are suitable for use in the form of
microdrops.
Examples F-4.1 to F-4.4: Granulates
Figure imgf000114_0001
The novel compound is dissolved in dichloromethane, the solution is sprayed onto the carrier and the solvent is then removed by distillation under vacuum.
Examples F-5.1 and F-5.2: Dusts
Figure imgf000114_0002
Ready for use dusts are obtained by intimately mixing all components.
Examples F-6.1 to F-6.3 : Wettable powders
Components F-6.1 F-6.2 F-6.3
Compound of Tables 1-11 25% 50% 75%
sodium lignin sulfonate 5% 5% - sodium lauryl sulfate 3% - 5%
sodium diisobutylnaphthalene sulfonate 6% 10% - octylphenolpolyethylene glycol ether 2%
(7 to 8 mol ethylenoxy units) highly dispersed silicic acid 5% 10% 10%
kaolin 62% 27% -
All components are mixed and the mixture is thoroughly ground in a suitable mill to give wettable powders which can be diluted with water to suspensions of any desired concentration. Example F7: Flowable concentrate for seed treatment
Figure imgf000115_0001
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by
microorganisms, by spraying, pouring or immersion.
Biological examples:
Biological Example 1 : fungicidal activity against Alternaria solani I tomato / leaf disc (early blight)
Tomato leaf disks cv. Baby were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf disks were incubated at 23 °C / 21°C (day/night) and 80% rh under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check disk leaf disks (5 - 7 days after application).
Compounds Tl .1.49, Tl .1.54, Tl .1.131, Tl .1.244, Tl .1.266 and T3.1.137 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 2: fungicidal activity against Blumeria graminis f. sp. tritici (Erysiphe graminis f. sp. tritici) I wheat / leaf disc preventative (Powdery mildew on wheat)
Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated by shaking powdery mildew infected plants above the test plates 1 day after application. The inoculated leaf disks were incubated at 20°C and 60% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate chamber and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check leaf segments (6 - 8 days after application).
Compounds Tl .1.22, Tl .1.26, Tl .1.29, Tl .1.49, Tl .1.54, Tl .1.72, Tl .1.107,
Tl .1.121, Tl .1.124, Tl .1.126, Tl .1.131, Tl .1.132, Tl .1.136, Tl .1.137, Tl .1.139, Tl .1.159, Tl .1.172, Tl .1.244, Tl .1.266, Tl .1.267, Tl .1.322, Tl . l . 326, Tl .1.376, T 1.1.432,1, Tl . l .432, Tl . l .44, T 1.1.476 and T3.1.137 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 3 : fungicidal activity against Botryotinia f ckeliana (Botrytis cinerea) I liquid culture (Grey mould)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application. Compounds Tl.1.7, Ti l l 1, Tl.1.16, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.31, Tl.1.32, Tl.1.36, Tl.1.37, Tl.1.42, Tl.1.49, Tl.1.54, Tl.1.61, Tl.1.66, Tl.1.67, Tl.1.71, Tl.1.104, Tl.1.107, Tl.1.109, Tl.1.114, Tl.1.121, Tl.1.122, Tl.1.124, Tl.1.126, Tl.1.131, Tl.1.132, Tl.1.136, Tl.1.137, Tl.1.139, Tl.1.142, Tl.1.144, Tl.1.154, Tl.1.159, Tl.1.161, Tl.1.167, Tl.1.169, Tl.1.172, Tl.1.179, Tl.1.184, Tl.1.196, Tl.1.244, Tl.1.257, Tl.1.266, Tl.1.267, Tl.1.322, Tl.l.326, Tl.1.346, Tl.1.347, Tl.1.376, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446, Tl.1.472, Tl.1.476, Tl.1.477 and T3.1.137 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 4: fungicidal activity against Gaeumannomyces graminis I liquid culture (Take-all of cereals)
Mycelial fragments of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores iss added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
Compounds Tl.1.7, Tl.1.9, Tl.1.16, Tl.l.17, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.31, Tl.1.32, Tl.1.36, Tl.1.37, Tl.1.42, Tl.l.57, Tl.1.61, Tl.1.67, Tl.1.71, Tl.l.107, Tl.l.121, Tl.l.122, Tl.l.126, Tl.l.131, Tl.l.132, Tl.l.136, Tl.l.137, Tl.l.139, Tl.l.142, Tl.l.161, Tl.l.162, Tl.l.167, Tl.l.172, Tl.l.192, Tl.l.196, Tl.1.256, Tl.1.257, Tl.1.261, Tl.1.266, Tl.1.267, Tl.1.286, Tl.1.322, Tl.l.326, Tl.l.346, Tl.l.347, Tl.1.376, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446, Tl.1.472, Tl.1.476, Tl.l.477 and T3.1.137 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 5: fungicidal activity against Glomerella lagenarium
(Colletotrichum lagenarium) I liquid culture (Anthracnose)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was measured photometrically 3-4 days after application.
Compounds Tl.1.7, Tl.1.9, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.32, Tl.1.49, Tl.1.54, Tl.1.61, Tl.1.71, Tl.1.72, Tl.1.104, Tl.1.107, Tl.1.109, Tl.1.114, Tl.1.119, Tl.1.121, Tl.1.122, Tl.1.124, Tl.1.131, Tl.1.132, Tl.1.137, Tl.1.139, Tl.1.144, Tl.1.154, Tl.1.159, Tl.1.161, Tl.1.162, Tl.1.167, Tl.1.172, Tl.1.184, Tl.1.196, Tl.1.204, Tl.1.244, Tl.1.249, Tl.1.262, Tl.1.274, Tl.1.284, Tl.l.326, Tl.1.347, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446, Tl.1.476, Tl.1.477 and T3.1.137 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 6: fungicidal activity against Monographella nivalis
(Microdochium nivale) / liquid culture (foot rot cereals)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
Compounds Tl.1.7, Tl.1.9, Tl.l.17, Tl.1.22, Tl.1.26, Tl.1.29, Tl.l.31, Tl.1.32, Tl.l.36, Tl.1.37, Tl.1.42, Tl.1.49, Tl.1.61, Tl.l.107, Tl.l.109, Tl.l.119, Tl.l.121, Tl.l.131, Tl.l.132, Tl.l.136, Tl.l.137, Tl.l.154, Tl.l.161, Tl.l.172, Tl.1.244, Tl.1.267, Tl.1.322, Tl.l.326, Tl.l.346, Tl.1.347, Tl.l.376, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446, Tl.1.476 and T3.1.137 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological Example 7: fungicidal activity against Mycosphaerella arachidis
(Cercospora arachidicola) I liquid culture (early leaf spot) Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
Compounds Tl.1.7, Tl.1.17, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.32, Tl.1.36, Tl.1.37, Tl.1.42, Tl.1.49, Tl.1.54, Tl.1.61, Tl.1.67, Tl.1.71, Tl.1.107, Tl.1.109, Tl.1.114, Tl.1.119, Tl.1.121, Tl.1.124, Tl.1.126, Tl.1.127. Tl.1.131, Tl.1.132, Tl.1.136, Tl.1.137, Tl.1.139, Tl.1.142, Tl.1.144, Tl.1.154, Tl.1.159, Tl.1.161, Tl.1.162, Tl.1.167, Tl.1.172, Tl.1.184, Tl.1.196, Tl.1.244, Tl.1.257, Tl.1.262, Tl.1.266, Tl.1.286, Tl.1.322, Tl.l.326, Tl.1.346, Tl.1.347, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446, Tl.1.472, Tl.1.476, Tl.1.477 and T3.1.137 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 8: fungicidal activity against Mycosphaerella graminicola (Septoria tritici) I liquid culture (Septoria blotch)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
Compounds Tl.1.7, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.32, Tl.1.36, Tl.1.37, Tl.1.49, Tl.1.54, Tl.1.61, Tl.1.71, Tl.l.107, Tl.l.109, Tl.l.114, Tl.l.121, Tl.l.124,
Tl.l.126, Tl.l.131, Tl.l.132, Tl.l.136, Tl.l.137, Tl.l.139, Tl.l.144, Tl.l.154, Tl.l.159, Tl.l.161, Tl.l.172, Tl.1.244, Tl.1.257, Tl.1.262, Tl.1.322, Tl.l.326, Tl.l.346, Tl.l.347, Tl.l.376, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446, Tl.1.476 and T3.1.137 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological Example 9: fungicidal activity against Phaeosphaeria nodorum (Septoria nodorum) / wheat / leaf disc preventative (Glume blotch)
Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 2 days after application. The inoculated test leaf disks were incubated at 20°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5-7 days after application). Compounds Tl.l.7, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.32, Tl.l.37, Tl.1.49, Tl.1.54, Tl.l.61, Tl.1.71, Tl.l.72, Tl.l.107, Tl.l.109, Tl.l.114, Tl.l.119, Tl.l.121, Tl.l.124, T.l.1.131, Tl.l.132, Tl.l.137, Tl.l.139, Tl.l.142, Tl.l.144, Tl.l.161, Tl.l.172, Tl.l.176, Tl.l.196, Tl.1.244, Tl.1.257, Tl.1.261, Tl.1.266, Tl.1.274, T.l.1.322, Tl.l.326, Tl.l.376, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446 and Tl.1.476 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 10: fungicidal activity against Phytophthora infestans I tomato / leaf disc preventative (late blight)
Tomato leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks were incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5-7 days after application).
Compounds Tl.l .49, Tl .1.54 and Tl .1.124 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological Example 11 : fungicidal activity against Plasmopara viticola I grape / leaf disc preventative (late blight)
Grape vine leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks were incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application).
Compounds T 1.1.29, T 1.1.49, T 1.1.54 and T 1.1.104 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 12: fungicidal activity against Puccinia recondita f. sp. tritici I wheat / leaf disc preventative (Brown rust)
Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 - 9 days after application).
Compounds Tl .1.22, Tl .1.26, Tl .1.49, Tl .1.54, Tl .1.61, Tl .1.67, Tl .1.107,
Tl .1.114, Tl .1.121, Tl .1.124, Tl .1.131, Tl .1.132, Tl .1.137, Tl .1.244, Tl .1.322, Tl . l . 326, Tl .1.376, Tl .1.431, Tl .1.432, Tl .1.441 and Tl .1.476 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 13 : fungicidal activity against Pyrenophora teres I barley / leaf disc preventative (Net blotch) Barley leaf segments cv. Hasso were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segmens were inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments were incubated at 20°C and 65% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5-7 days after application).
Compounds Tl.1.7, Tl.1.22, Tl.1.26, Tl.1.29, Tl.1.32, Tl.1.37, Tl.1.49, Tl.1.54, Tl.1.61, Tl.1.71, Tl.1.107, Tl.1.114, Tl.1.121, Tl.1.124, Tl.1.126, Tl.1.131, Tl.1.132, Tl.1.136, Tl.1.137, Tl.1.139, Tl.1.144, Tl.1.167, Tl.1.172, Tl.1.184, Tl.1.189, Tl.1.196, Tl.1.244, Tl.1.266, Tl.1.267, Tl.1.322, Tl.l.326, Tl.1.346, Tl.1.376, Tl.1.431, Tl.1.432, Tl.1.441, Tl.1.446, T1.1.476T1.1.477 and T3.1.137 and from table 13 compounds 1 and 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological Example 14: fungicidal activity against Thanatephorus cucumeris
(Rhizoctonia solani) I liquid culture (foot rot, damping-off)
Mycelia fragments of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format), the nutrient broth containing the fungal material was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application. Compounds Tl.1.7, Tl.1.26, Tl.1.32, Tl.1.61, Tl.l.107, Tl.l.121, Tl.l.126,
Tl.l.131, Tl.l.137, Tl.l.142, Tl.l.172, Tl.1.266, Tl.l.326, Tl.1.431, Tl.1.432, Tl.l.441 and T3.1.137 and from table 13 compound 2 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

Claims

Claims
1. A compound of formula I
Figure imgf000123_0001
wherein:
R1 is hydrogen, halogen, cyano, Ci-6alkyl, C3-6cycloalkyl, Ci-6haloalkyl, Ci-6alkoxy,
Ci-6haloalkoxy or Ci-6alkylthio;
R 2 , R 5 , R 6° and R 1' are, independently from each other, hydrogen, hydroxy, halogen, Ci-6alkyl, C3-6cycloalkyl or Ci-6alkoxy;
A is heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio or heteroarylalkynyl; or a salt or a N-oxide thereof.
2. A compound of formula I according to claim 1, wherein
R1 is hydrogen, halogen, cyano, Ci-6alkyl, C3-6cycloalkyl, Ci-6haloalkyl, Ci-6alkoxy or Ci-6haloalkoxy;
R 2 , R 5 , R 6° and R 1' are, independently from each other, hydrogen, halogen, Ci_ 6alkyl, C3-6cycloalkyl or Ci-6alkoxy; and
A is heteroaryl, heteroarylalkyl, heteroarylthio or heteroalkynyl.
3. A compound of formula I according to claim 2, wherein
R1 is hydrogen, halogen, Ci-6alkyl, Ci-6haloalkyl, Ci-6alkoxy or Ci-6haloalkoxy;
R 2 , R 5 , R 6° and R 1' are, independently from each other, hydrogen, halogen, Ci_ 6alkyl or Ci-6alkoxy; and
A is heteroaryl, heteroarylalkyl or heteroarylthio.
4. A compound of formula I according to claim 3, wherein
R1 is hydrogen, halogen, Ci-6alkyl, Ci-6haloalkyl or Ci-6alkoxy;
R 2 , R 5 , R 6° and R1' are, independently from each other, hydrogen, Ci-6alkyl or Ci-6alkoxy; and
A is heteroaryl or heteroarylalkyl.
5. A compound of formula I according to claim 4, wherein
R1 is hydrogen, halogen, Ci-6alkyl or Ci-6alkoxy;
R 2 , R 5 , R 6° and R1' are, independently from each other, hydrogen, Ci-6alkyl or Ci-6alkoxy; and
A is heteroaryl or heteroarylalkyl.
6. A method of controlling or preventing infestation of useful plants by
phytopathogenic microorganisms, wherein a compound of formula I according to claim 1 or a composition, comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
7. A composition for controlling and protecting against phytopathogenic
microorganisms, comprising a compound of formula I according to claim 1 and at least one auxiliary.
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Citations (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0353191A2 (en) 1988-07-29 1990-01-31 Ciba-Geigy Ag DNA sequences encoding polypeptides having beta-1,3-glucanase activity
EP0367474A1 (en) 1988-11-01 1990-05-09 Mycogen Corporation Novel bacillus thuringiensis isolate denoted b.t. ps81gg, active against lepidopteran pests, and a gene encoding a lepidopteran-active toxin
EP0374753A2 (en) 1988-12-19 1990-06-27 American Cyanamid Company Insecticidal toxines, genes coding therefor, antibodies binding them, transgenic plant cells and plants expressing these toxines
EP0392225A2 (en) 1989-03-24 1990-10-17 Ciba-Geigy Ag Disease-resistant transgenic plants
WO1990013651A1 (en) 1989-05-09 1990-11-15 Imperial Chemical Industries Plc Bacterial genes
EP0401979A2 (en) 1989-05-18 1990-12-12 Mycogen Corporation Novel bacillus thuringiensis isolates active against lepidopteran pests, and genes encoding novel lepidopteran-active toxins
EP0427529A1 (en) 1989-11-07 1991-05-15 Pioneer Hi-Bred International, Inc. Larvicidal lectins and plant insect resistance based thereon
EP0451878A1 (en) 1985-01-18 1991-10-16 Plant Genetic Systems, N.V. Modifying plants by genetic engineering to combat or control insects
WO1993007278A1 (en) 1991-10-04 1993-04-15 Ciba-Geigy Ag Synthetic dna sequence having enhanced insecticidal activity in maize
WO1995033818A2 (en) 1994-06-08 1995-12-14 Ciba-Geigy Ag Genes for the synthesis of antipathogenic substances
WO1995034656A1 (en) 1994-06-10 1995-12-21 Ciba-Geigy Ag Novel bacillus thuringiensis genes coding toxins active against lepidopteran pests
WO1997033890A1 (en) 1996-03-11 1997-09-18 Novartis Ag Pyrimidin-4-one derivatives as pesticide
WO2002015701A2 (en) 2000-08-25 2002-02-28 Syngenta Participations Ag Bacillus thuringiensis crystal protein hybrids
WO2003018810A2 (en) 2001-08-31 2003-03-06 Syngenta Participations Ag Modified cry3a toxins and nucleic acid sequences coding therefor
WO2003052073A2 (en) 2001-12-17 2003-06-26 Syngenta Participations Ag Novel corn event
WO2006010570A1 (en) * 2004-07-23 2006-02-02 Basf Aktiengesellschaft 2-(pyridin-2-yl)-pyrimidines and their use for controlling pathogenic fungi
WO2006087343A1 (en) 2005-02-16 2006-08-24 Basf Aktiengesellschaft Pyrazole carboxylic acid anilides, method for the production thereof and agents containing them for controlling pathogenic fungi
WO2007048556A1 (en) 2005-10-25 2007-05-03 Syngenta Participations Ag Heterocyclic amide derivatives useful as microbiocides
WO2008013925A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008148570A1 (en) 2007-06-08 2008-12-11 Syngenta Participations Ag Pyrazole carboxylic acid amides useful as microbiocides
WO2010123791A1 (en) 2009-04-22 2010-10-28 E. I. Du Pont De Nemours And Company Solid forms of an azocyclic amide
WO2010136475A1 (en) * 2009-05-29 2010-12-02 Syngenta Participations Ag Substituted quinazolines as fungicides
WO2011051243A1 (en) 2009-10-29 2011-05-05 Bayer Cropscience Ag Active compound combinations

Patent Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0451878A1 (en) 1985-01-18 1991-10-16 Plant Genetic Systems, N.V. Modifying plants by genetic engineering to combat or control insects
EP0353191A2 (en) 1988-07-29 1990-01-31 Ciba-Geigy Ag DNA sequences encoding polypeptides having beta-1,3-glucanase activity
EP0367474A1 (en) 1988-11-01 1990-05-09 Mycogen Corporation Novel bacillus thuringiensis isolate denoted b.t. ps81gg, active against lepidopteran pests, and a gene encoding a lepidopteran-active toxin
EP0374753A2 (en) 1988-12-19 1990-06-27 American Cyanamid Company Insecticidal toxines, genes coding therefor, antibodies binding them, transgenic plant cells and plants expressing these toxines
EP0392225A2 (en) 1989-03-24 1990-10-17 Ciba-Geigy Ag Disease-resistant transgenic plants
WO1990013651A1 (en) 1989-05-09 1990-11-15 Imperial Chemical Industries Plc Bacterial genes
EP0401979A2 (en) 1989-05-18 1990-12-12 Mycogen Corporation Novel bacillus thuringiensis isolates active against lepidopteran pests, and genes encoding novel lepidopteran-active toxins
EP0427529A1 (en) 1989-11-07 1991-05-15 Pioneer Hi-Bred International, Inc. Larvicidal lectins and plant insect resistance based thereon
WO1993007278A1 (en) 1991-10-04 1993-04-15 Ciba-Geigy Ag Synthetic dna sequence having enhanced insecticidal activity in maize
WO1995033818A2 (en) 1994-06-08 1995-12-14 Ciba-Geigy Ag Genes for the synthesis of antipathogenic substances
WO1995034656A1 (en) 1994-06-10 1995-12-21 Ciba-Geigy Ag Novel bacillus thuringiensis genes coding toxins active against lepidopteran pests
WO1997033890A1 (en) 1996-03-11 1997-09-18 Novartis Ag Pyrimidin-4-one derivatives as pesticide
WO2002015701A2 (en) 2000-08-25 2002-02-28 Syngenta Participations Ag Bacillus thuringiensis crystal protein hybrids
WO2003018810A2 (en) 2001-08-31 2003-03-06 Syngenta Participations Ag Modified cry3a toxins and nucleic acid sequences coding therefor
WO2003052073A2 (en) 2001-12-17 2003-06-26 Syngenta Participations Ag Novel corn event
WO2006010570A1 (en) * 2004-07-23 2006-02-02 Basf Aktiengesellschaft 2-(pyridin-2-yl)-pyrimidines and their use for controlling pathogenic fungi
WO2006087343A1 (en) 2005-02-16 2006-08-24 Basf Aktiengesellschaft Pyrazole carboxylic acid anilides, method for the production thereof and agents containing them for controlling pathogenic fungi
WO2007048556A1 (en) 2005-10-25 2007-05-03 Syngenta Participations Ag Heterocyclic amide derivatives useful as microbiocides
WO2008013925A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008148570A1 (en) 2007-06-08 2008-12-11 Syngenta Participations Ag Pyrazole carboxylic acid amides useful as microbiocides
WO2010123791A1 (en) 2009-04-22 2010-10-28 E. I. Du Pont De Nemours And Company Solid forms of an azocyclic amide
WO2010136475A1 (en) * 2009-05-29 2010-12-02 Syngenta Participations Ag Substituted quinazolines as fungicides
WO2011051243A1 (en) 2009-10-29 2011-05-05 Bayer Cropscience Ag Active compound combinations

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANGELO ALBINI; SILVIO PIETRA: "Heterocyclic N-oxides", 1991, CRC PRESS
COLBY, S.R.: "Calculating synergistic and antagonistic responses of herbicide combination", WEEDS, vol. 15, 1967, pages 20 - 22, XP001112961

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019112408A (en) * 2013-03-15 2019-07-11 ダウ アグロサイエンシィズ エルエルシー 4-amino-6-(heterocyclic)picolinates and 6-amino-2-(heterocyclic)pyrimidine-4-carboxylates and their use as herbicides
CN104447518A (en) * 2014-12-06 2015-03-25 哈尔滨工业大学 Synthesis method for flexible dipyridine derivative 6-bromine-2-pyridine methylenepyridine
CN104628632A (en) * 2015-03-03 2015-05-20 哈尔滨工业大学 Pyridine derivative [2,2'-dipyridyl]-6-yl(6-methoxy pyridine-2-yl)ketone and synthesis method thereof
CN104672128A (en) * 2015-03-03 2015-06-03 哈尔滨工业大学 Flexible bipyridine derivative 6-methoxy-2-pyridine methylene pyridine and synthetic method thereof
CN104860878A (en) * 2015-06-10 2015-08-26 哈尔滨工业大学 Pyridine derivative pyridine-2,6-disubstituted bis(6-methoxyl pyridine-2-yl) ketone and synthesis method thereof
CN104860877A (en) * 2015-06-10 2015-08-26 哈尔滨工业大学 Pyridine derivative 6-methoxyl-6'-[(6-methoxypyridine-2-yl)methyl]-2,2'-pyridine and synthesis method thereof

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