WO2012117021A2 - Nouveaux éthers d'oxime microbiocides - Google Patents

Nouveaux éthers d'oxime microbiocides Download PDF

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WO2012117021A2
WO2012117021A2 PCT/EP2012/053444 EP2012053444W WO2012117021A2 WO 2012117021 A2 WO2012117021 A2 WO 2012117021A2 EP 2012053444 W EP2012053444 W EP 2012053444W WO 2012117021 A2 WO2012117021 A2 WO 2012117021A2
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alkyl
halogen
alkoxy
phenyl
formula
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PCT/EP2012/053444
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WO2012117021A3 (fr
Inventor
Stephan Trah
Kurt Nebel
Martin Pouliot
Laura Quaranta
Daniel Stierli
Werner Zambach
Andrea Bortolato
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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
    • C07D401/14—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
    • 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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2

Definitions

  • the present invention relates to novel microbiocidally active, in particular fungicidally active, oxime derivatives. It further relates to intermediates used in the preparation of these compounds, to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
  • Fungicidally active bisoximes are described in WO08074418 and WO12001040.
  • the present invention accordingly relates to oxime derivatives of formula (I)
  • D 1 represents N or C-Y 1 ;
  • D 2 represents N or C-Y 2 ;
  • D 3 represents N or C-Y 5 ;
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, halogen, CN,
  • each R 1 independently of one another represents hydrogen, d-C 8 alkyl, C 3 -C 8 cycloalkyi, C 3 -C 8 alkenyl, C 3 -C 8 alkynyl, Ci-C 4 alkylsulphonyl, phenyl, benzyl or a 5- or 6-membered heterocycle containing one to three heteroatoms independently selected from O, S and N, providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, wherein the alkyl, cycloalkyi, alkenyl, alkynyl, phenyl, benzyl and heterocycle are optionally substituted by one or more groups
  • halogen independently selected from halogen, CN, NH 2 , N0 2 , OH, d-C 4 alkyl, Ci-C 4 -haloalkyl, Ci-C 4 alkoxy, Ci-C 4 haloalkoxy, Ci-C 4 -alkyl-Ci-C 4 -alkoxy and Ci-C 4 -alkoxy-Ci-C 4 -alkyl;
  • each R 2 independently of one another represents hydrogen, d-C 8 alkyl, C 3 -C 8 cycloalkyi, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, phenyl, benzyl or pyridyl, wherein the alkyl, cycloalkyi, alkenyl, alkynyl, phenyl, benzyl and pyridyl are optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, d-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and d-C 4 haloalkoxy;
  • each R 3 independently of one another represents hydrogen, OH, Ci-C 8 alkyl, Ci-C 8 alkoxy, Ci-C 8 -alkoxy-Ci-C 4 -alkyl, C 3 -C 8 alkenyl, C 3 -C 8 alkynyl, or COR 2 , wherein the alkyl, alkoxy, alkenyl and alkynyl are optionally substituted by one or more halogen;
  • radicals R 3 wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • cycle formed is optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, d-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy; G 1 and G 2 independently of one another represent -C(R R 5 )-;
  • G 3 represents -C(R R 5 )-, O, N(R 6 ) or S;
  • each R 4 and R 5 independently of one another represent hydrogen, halogen, d-C 4 alkyl, Ci-C 4 haloalkyi, Ci-C 4 alkoxy or Ci-C 4 haloalkoxy;
  • R 6 represents hydrogen, OH, CrC 4 alkyl, Ci-C 4 alkoxy, C 3 -C 6 cycloalkyl, Ci-C 8
  • p 0, 1 or 2;
  • X represents X-2, X-3, X-4 or X-5:
  • each R 7 and R 8 independently of one another represent hydrogen, halogen, CN, OH, d- C 4 alkyl, Ci-C 4 haloalkyi or phenyl, wherein the phenyl is optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkyl, d-C 4 haloalkyi, Ci-C 4 alkoxy and d-C 4 haloalkoxy;
  • R 7 and R 8 together with the carbon atom to which they are attached may form a C 3 - C 6 cycloalkyl group or a C 3 -C 6 halocycloalkyl group;
  • each R 9 and R 10 independently of one another represent hydrogen, halogen, Ci-C 4 alkyl or Ci-C 4 haloalkyi;
  • each R 11 , R 12 , R 13 and R 14 independently of one another represent hydrogen, halogen,
  • CN OH, Ci-C 4 alkyl, Ci-C 4 haloalkyi, d-C 4 alkoxy or phenyl, wherein phenyl is optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkyl, d- C 4 haloalkyi, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy;
  • R 11 and R 12 together with the carbon atom to which they are attached may form a C 3 - C 6 cycloalkyl group or a C 3 -C 6 halocycloalkyl group;
  • groupings X-2, X-3, X-4 and X-5 contain at most one ring which contains either only one of the radicals Z 1 to Z 14 or two radicals Z 1 to Z 14 or three radicals Z 1 to Z 14 or four radicals Z 1 to Z 14 as ring members; and wherein radicals Z 1 , Z 3 , Z 6 and Z 10 are not substituted by OH; and wherein none of Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , Z 8 , Z 9 , Z 10 , Z 11 , Z 12 , Z 1 Z 14 represent a carbon atom substituted by two OH;
  • W represents cycle W-l, W-2, W-3, W-4, W-5, W-6 or W-7:
  • R 15 , R 16 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, CN, N0 2 , Ci-Cs alkyl, C 3 -C 8 cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, phenyl, a 5- or 6-membered heterocycle containing one to three heteroatoms independently selected from O, S and N, providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, benzyl, OR 1 , COR 2 , SH, Ci-C 8 alkylthio, Ci-C 8 alkylsulphinyl, Ci-C 8 alkylsulphonyl, phenylthio, phenylsulphinyl, phenylsulphonyl, N(R 3 ) 2 , CO ⁇ 1 , 0(CO)R 2 , CON(R 3
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a partially or fully unsaturated 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from O, S, N and N(R 3 ), providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, and wherein the ring formed by R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 is optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, d-C 4 haloalkyi, d-C 4 alkoxy and d-C 4 haloalkoxy;
  • Halogen either as a lone substituent or in combination with another substituent (e.g. haloalkyi) is generally fluorine, chlorine, bromine or iodine, and usually fluorine, chlorine or bromine.
  • Each alkyl moiety (including the alkyl moiety of alkoxy, alkylthio, etc.) is a straight or branched chain and, depending on the number of carbon atoms it contains, is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, /so-propyl, sec-butyl, /so-butyl, te t-butyl, neo-pentyl, n-heptyl or 1, 3-d i methyl butyl, and usually methyl or ethyl.
  • alkenyl and alkynyl groups can be mono- or di-unsaturated and examples thereof are derived from the above mentioned alkyl groups.
  • the alkenyl group is an unsaturated straight or branched chain having a carbon-carbon double bond and, depending on the number of carbon atoms it contains, is, for example ethenyl, 1-propenyl, 2-propenyl, 1-methyl-ethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl- 1-propenyl, 2-methyl-l-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-l-butenyl, 2-methyl-l-butenyl, 3-methyl-l-butenyl, l-methyl-2- butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3-butenyl, 3- methyl-3-butenyl, l,l-dimethyl-2-propenyl, 1,2-dimethyl-l-prop
  • the alkynyl group is an unsaturated straight or branched chain having a carbon-carbon triple bond and, depending on the number of carbon atoms it contains, is, for example ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl, 1- pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 3-methyl-l-butynyl, l-methyl-2-butynyl, 1- methyl-3-butynyl, 2-methyl-3-butynyl, l,l-dimethyl-2-propynyl, l-ethyl-2-propynyl, 1- hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3-methyl-l-pent
  • Haloalkyl moieties are alkyl moieties which are substituted by one or more of the same or different halogen atoms and are, for example, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2,2- difluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 1-fluoroethyl, 2-chloroethyl, pentafluoroethyl, l,l-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl, and typically trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, /so-propoxy, n-butoxy, /so-butoxy, sec-butoxy and tert-butoxy, and usually methoxy or ethoxy.
  • Haloalkoxy 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, and usually difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
  • Alkylthio is, for example, methylthio, ethylthio, propylthio, /so-propylthio, n-butylthio, /so-butylthio, sec-butylthio or tert-butylthio, and usually methylthio or ethylthio.
  • Alkylsulphonyl is, for example, methylsulphonyl, ethyl sulphonyl, propyl sulphonyl, iso- propylsulphonyl, n-butylsulphonyl, /so-butylsulphonyl, sec-butylsulphonyl or tert- butylsulphonyl, and usually methylsulphonyl or ethylsulphonyl.
  • Alkylsulphinyl is, for example, methylsulphinyl, ethylsulphinyl, propylsulphinyl, iso- propylsulphinyl, n-butylsulphinyl, /so-butylsulphinyl, sec-butylsulphinyl or tert-butylsulphinyl, and usually methylsulphinyl or ethylsulphinyl.
  • Cycloalkyl may be saturated or partially unsaturated, preferably fully saturated, and is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, /so-propoxymethyl or /so-propoxyethyl.
  • Aryl includes phenyl, naphthyl, anthracyl, fluorenyl and indanyl, but is usually phenyl.
  • Carbocycle includes cycloalkyl groups and aryl groups.
  • Heterocycloalkyl is a non-aromatic ring that may be saturated or partially unsaturated, preferably fully saturated, containing carbon atoms as ring members and at least one heteroatom selected from O, S and N as ring members.
  • Examples include oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1,3-dioxolanyl, 1,4-dioxanyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, oxazinanyl, morpholinyl, thiomorpholinyl, imidazolidinyl, pyrazolidinyl and piperazinyl, preferably morpholinyl, pyrrolidinyl, piperdinyl and piperazinyl, more preferably morpholinyl and pyrollidinyl.
  • Heteroaryl is, for example, a monovalent monocyclic or bicyclic aromatic hydrocarbon radical.
  • monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, and thiadiazolyl.
  • bicyclic groups include quinolinyl, cinnolinyl, quinoxalinyl, benzimidazolyl, benzothiophenyl, and benzothiadiazolyl.
  • Monocyclic heteroaryl groups are preferred, preferably pyridyl, pyrrolyl, imidazolyl and triazolyl, e.g. 1,2,4 triazolyl, pyridyl and imidazolyl being most preferred.
  • heterocycle and “heterocyclic ring” are used interchangeably and are defined to include heterocycloalkyl and heteroaryl groups. Any reference herein to a heterocycle or heterocyclic ring preferably refers to the specific examples given under the definition of heteroaryl and heterocycloalkyl above, and are preferably morpholinyl, pyrrolidinyl, piperdinyl, piperazinyl pyridyl, pyrrolyl, imidazolyl and triazolyl, e.g. 1,2,4 triazolyl, more preferably morpholinyl, pyrollidinyl, pyridyl and imidazolyl.
  • No heterocycle contains adjacent oxygen atoms, adjacent sulphur atoms, or adjacent oxygen and sulphur atoms.
  • a moiety is indicated as being (optionally) substituted, e.g. alkyl, this includes those moieties where they are part of a larger group, e.g. the alkyl in the alkylthio group. The same applies, e.g. to the phenyl moiety in phenylthio etc.
  • a moiety is indicated as being optionally substituted by one or more other groups, preferably there are one to five optional substituents, more preferably one to three optional substituents.
  • a moiety is substituted by a cyclic group, e.g. aryl, heteroaryl, cycloalkyi, preferably there are no more than two such substituents, more preferably no more than one such substituent.
  • D 1 represents N or C-Y 1 .
  • D 1 represents C-Y 1 .
  • D 2 represents N or C-Y 2 .
  • D 2 represents C-Y 2 .
  • both D 1 and D 2 be N.
  • D 3 represents N or C-Y 5 .
  • D 3 represents C-Y 5 .
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, halogen, CN, N0 2 , Ci-Cs alkyl, C 3 -C 8 cycloalkyi, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, phenyl, a 5- or 6-membered heterocycle containing one to three heteroatoms independently selected from O, S and N, providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, (e.g.
  • heterocycle as defined herein, preferably morpholinyl, pyrrolidinyl, piperdinyl, piperazinyl, pyridyl, pyrrolyl, imidazolyl or triazolyl, e.g.
  • 1,2,4 triazolyl more preferably morpholinyl, pyrollidinyl, pyridyl or imidazolyl
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, halogen, CN, OR 1 , Ci-C 8 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyi, phenyl, pyridyl, C0 2 R 1 , N(R 3 ) 2 , NR 3 COR 2 , SH, Ci-C 8 -alkylthio, Ci-C 8 -alkylsulphinyl, Ci-C 8 -alkylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl, wherein the alkyl, alkenyl, cycloalkyi, phenyl and pyridyl are optionally substituted by one or more groups, e.g.
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, halogen, OR 1 , CN, C r C 4 alkyl, C 3 -C 6 cycloalkyl, N(R 3 ) 2 , phenyl, C0 2 R 1 or NR 3 COR 2 , wherein the alkyl, cycloalkyl and phenyl are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, d-C 4 alkyl, Ci-C 4 - haloalkyi, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, halogen, OH, CN, d-C 4 alkyl, Ci-C 4 alkoxy, C 3 -C 6 alkenyloxy, C 3 -C 6 cycloalkyl, N(R 3 ) 2 , phenyl or GC ⁇ R 1 , wherein the alkyl, alkoxy, alkenyloxy, cycloalkyl and phenyl are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, d-C 4 alkyl, Ci-C 4 -haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, d-C 4 alkyl, CN or d-C 4 alkoxy, wherein the alkyl and alkoxy are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a partially or fully unsaturated 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from O, S, N and N(R 3 ), providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, and wherein the ring formed by Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 is optionally substituted by one or more groups, e.g.
  • one to five groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, Ci-C 4 haloalkyi, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7- membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from N and N(R 3 ), and wherein the ring formed by Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 is optionally substituted by one or more groups, e.g.
  • one to five groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, Ci-C 4 haloalkyi, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7- membered carbocyclic ring wherein the ring formed by Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 is optionally substituted by one or more groups, e.g. one to five groups,
  • Y 1 and Y 2 independently of one another represent hydrogen, d-C 4 alkyl, CN or d-C 4 alkoxy, wherein the alkyl and alkoxy are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy and Y 3 is as defined according to any of the defintions above.
  • Y 4 , Y 5 and Y 6 other than when forming a carbocyclic ring or heterocyclic ring with each other, independently of one another represent hydrogen, CN, OR 1 , NH 2 , halogen, Ci-C 8 alkyl, Ci-C 8 haloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 8 cycloalkyl, SH, Ci-C 8 alkylthio, N(R 3 ) 2 , NR 3 COR 2 , phenyl or pyridyl, wherein phenyl and pyridyl are optionally substituted by one or more groups, e.g. one to five groups,
  • each R 1 independently represents one another represents hydrogen, d-C 8 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 alkenyl, C 3 -C 8 alkynyl, benzyl, phenyl or pyridyl, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, benzyl and pyridyl are optionally substituted by one or more groups, e.g.
  • each R 2 independently of one another represents Ci-C 4 -alkyl or Ci-C 4 haloalkyl;
  • each R 3 independently of one another represent hydrogen or Ci-C 4 alkyl
  • radicals R 3 wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • Y 4 , Y 5 , and Y 6 other than when forming a carbocyclic ring or heterocyclic ring each other, independently of one another represent hydrogen, CN, OH, NH 2 , halogen, C1-C4 alkyl, d-C haloalkyl, d-C alkoxy, d-C haloalkoxy, C 3 -C 6 cycloalkyl, N(R 3 ) 2 , NR 3 COR 2 or phenyl, wherein phenyl is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, methyl, CN, methoxy, halomethyl and halomethoxy;
  • each R 2 independently represents d-C 4 -alkyl or d-C 4 haloalkyl
  • each R 3 independently of one another represent hydrogen or Ci-C 4 alkyl
  • radicals R 3 wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • Each R 1 independently of one another represents hydrogen, d-C 8 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 alkenyl, C 3 -C 8 alkynyl, d-C 4 alkylsulphonyl, phenyl, benzyl or a 5- or 6-membered heterocycle containing one to three heteroatoms independently selected from O, S and N, providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, benzyl and heterocycle are optionally substituted by one or more groups, e.g.
  • the heterocycle is preferably one as defined herein, preferably morpholinyl, pyrrolidinyl, piperdinyl, piperazinyl, pyridyl, pyrrolyl, imidazolyl or triazolyl, e.g. 1,2,4 triazolyl, more preferably morpholinyl, pyrollidinyl, pyridyl or imidazolyl.
  • each R 1 independently of one another represents hydrogen, Ci-C 8 alkyl, d-C 8 haloalkyl, C 3 -C 8 alkenyl, C 3 -C 8 haloalkenyl, C 3 -C 8 haloalkynyl, phenyl, benzyl or pyridyl, wherein the phenyl, benzyl and pyridyl are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, Ci-Grhaloalkyl, Ci-C 4 alkoxy and d-C 4 haloalkoxy.
  • each R 1 independently of one another represents hydrogen, Ci-C 4 alkyl or Ci-C haloalkyl.
  • Each R 2 independently of one another represents hydrogen, d-C 8 alkyl, C 3 -C 8 cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, phenyl, benzyl or pyridyl, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, benzyl and pyridyl are optionally substituted by one or more groups, e.g.
  • one to five groups independently selected from halogen, CN, NH 2 , N0 2 , OH, d-C 4 alkyl, d- C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • each R 2 independently of one another represents hydrogen, d-C 8 alkyl or d- C 8 haloalkyl.
  • each R 2 independently of one another represents hydrogen, Ci-C 4 alkyl or Ci-C 4 haloalkyl.
  • Each R 3 independently of one another represents hydrogen, OH, Ci-C 8 alkyl, Ci-C 8 alkoxy, Ci-C 8 -alkoxy-Ci-C 4 -alkyl, C 3 -C 8 alkenyl, C 3 -C 8 alkynyl, or COR 2 , wherein the alkyl, alkoxy, alkenyl and alkynyl are optionally substituted by one or more, e.g. one to five, halogen;
  • radicals R 3 when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different; wherein when two radicals R 3 are attached to the same nitrogen atom, both of these radicals cannot be OH, Ci-C 4 alkoxy or Ci-C 4 haloalkoxy;
  • cycle formed is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • groups e.g. one to five groups, independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • each R 3 independently of one another represents hydrogen, d-C 8 alkyl or
  • radicals R 3 wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • each R 3 independently of one another represents hydrogen or Ci-C 4 alkyl
  • radicals R 3 wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • G 1 and G 2 independently of one another represent -C(R R 5 )-;
  • G 3 represents -C(R R 5 )-, O, N(R 3 ) or S;
  • each R 4 and R 5 independently of one another represent hydrogen, halogen, d-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy or d-C 4 haloalkoxy;
  • R 6 represents hydrogen, OH, CrC 4 alkyl, CrC 4 alkoxy, C3-C5 cycloalkyl, Ci-C 8
  • G 1 , G 2 and G 3 represent C(R 21 ) 2 , wherein each R 21 independently of one another represents hydrogen or CrC 4 alkyl.
  • p 0, 1 or 2.
  • p is 1.
  • X represents X-2, X-3, X-4 or X-5.
  • X represents X-3 or X-5.
  • X represents X-3.
  • C CR 9 R 10 ; more preferably methylene.
  • X is X-2, preferably one of Z 1 and Z 2 is methylene or halomethylene, preferably methylene.
  • Z 3 , Z 4 and Z 5 are substituted only by hydrogen or halogen, preferably hydrogen, or Z 4 and Z 5 together are -C ⁇ C-, more preferably two of Z 3 , Z 4 and Z 5 are independently methylene or halomethylene, preferably methylene.
  • Z 3 and Z 5 are methylene or halomethylene, preferably methylene.
  • X is X-4
  • Z 6 , Z 7 , Z 8 and Z 9 are substituted only by hydrogen or halogen, preferably hydrogen, with the proviso that Z 7 and Z 8 or Z 8 and Z 9 together may be -C ⁇ C-, more preferably at least three of Z 6 , Z 7 , Z 8 and Z 9 are independently methylene or halomethylene, preferably methylene.
  • Z 10 , Z 11 , Z 12 , Z 13 and Z 14 are substituted only by hydrogen or halogen, preferably hydrogen, with the proviso that Z 11 and Z 12 or Z 12 and Z 13 or Z 13 and Z 14 together may be -C ⁇ C-, more preferably four of Z 10 , Z 11 , Z 12 , Z 13 and Z 14 are independently methylene or halomethylene, preferably methylene.
  • Z 10 , Z 11 , Z 13 and Z 14 are independently methylene or halomethylene, preferably methylene.
  • Radicals Z 1 , Z 3 , Z 6 and Z 10 are not substituted by OH, and none of Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , Z 8 , Z 9 , Z 10 , Z 11 , Z 12 , Z 13 and Z 14 represent a carbon atom substituted by two OH groups.
  • Each R 7 and R 8 independently of one another represent hydrogen, halogen, CN, OH, d- C 4 alkyl, Ci-C 4 haloalkyl or phenyl, wherein the phenyl is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, d-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy;
  • R 7 and R 8 together with the carbon atom to which they are attached may form a C 3 -
  • each R 7 and R 8 independently of one another represent hydrogen, halogen, CN, OH, C1-C4 alkyl or d-C 4 haloalkyi.
  • Each R 9 and R 10 independently of one another represent hydrogen, halogen, Ci-C 4 alkyl or Ci-C 4 haloalkyi.
  • each R 9 and R 10 independently of one another represent hydrogen, halogen, methyl or halomethyl.
  • Each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH, Ci-C 4 alkyl, Q-Q haloalkyi, d-C 4 alkoxy or phenyl, wherein phenyl is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, Ci-C 4 alkyl, Ci-C 4 haloalkyi, d-C 4 alkoxy and Ci-C 4 haloalkoxy;
  • R 11 and R 12 together with the carbon atom to which they are attached may form a C 3 - C 6 cycloalkyl group or a C 3 -C 6 halocycloalkyl group.
  • each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH, Ci-C 4 alkyl, Ci-C 4 haloalkyi, d-C 4 alkoxy or phenyl, wherein the phenyl is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, methyl, halomethyl, methoxy and halomethoxy;
  • R 11 and R 12 together with the carbon atom to which they are attached may form a C 3 - C 6 cycloalkyl group or a C 3 -C 6 halocycloalkyl group.
  • each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH, Ci-C 4 alkyl, Ci-C 4 haloalkyi, CrC 4 alkoxy or phenyl, wherein the phenyl is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, methyl, halomethyl, methoxy and halomethoxy.
  • each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH, d-C 4 alkyl, d-C 4 haloalkyi, d-C 4 alkoxy.
  • R 11 and R 12 represent hydrogen.
  • Each R 13 and R 14 independently of one another represent hydrogen, halogen, CN, OH, Ci-C 4 alkyl, Ci-C 4 haloalkyi or phenyl, wherein phenyl is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, d-C 4 alkyl, Ci-C 4 haloalkyi, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • each R 13 and R 14 independently of one another represent hydrogen, halogen,
  • CN OH, Ci-C 4 alkyl, Ci-C 4 haloalkyi or phenyl, wherein the phenyl is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, methyl, halomethyl, methoxy and halomethoxy.
  • W represents cycle W-l, W-2, W-3, W-4, W-5, W-6 or W-7:
  • W represents cycle W-1, W-2 or W-4.
  • W represents W-1 or W-2.
  • W represents cycle W-1.
  • R 15 , R 16 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, CN,
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a partially or fully unsaturated 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from O, S, N and N(R 3 ), providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, (e.g.
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a ring system selected from isoquinoline; 5,6,7,8-tetrahydro-isoquinoline; 6,7-dihydro-5H-[2]pyrindine; 3,4- dihydro-lH-pyrano[3,4-c]pyridine; 6,7,8,9-tetrahydro-5H-cyclohepta[c]pyridine;
  • one to five groups independently selected from halogen, CN, NH 2 , N0 2 , OH, d-d alkyl, Crd haloalkyi, d-d alkoxy and d-d haloalkoxy.
  • R 15 , R 16 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, CN, OR 1 , d-C 8 alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyi, phenyl, pyridyl, benzyl, N(R 3 ) 2 , NR 3 COR 2 , SH, d-C 8 alkylthio, Ci-C 8 alkylsulphinyl, Ci-C 8 alkylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl, wherein the alkyl, alkenyl, cycloalkyi, phenyl, pyridyl and benzyl are optionally substituted by one or more groups, e.g. one to five groups,
  • halogen independently selected from halogen, CN, OR 1 , Crd alkyl and d-d haloalkyi.
  • R 15 , R 16 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, OR 1 , CN, Crd alkyl, C 3 -C 6 cycloalkyi, N(R 3 ) 2 , d-C 4 alkylthio, d-C 4 alkylsulphinyl, d-C 4 alkylsulphonyl, phenyl, benzyl, C0 2 R J or NR 3 COR 2 wherein the alkyl, cycloalkyi, phenyl and benzyl are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, d-C 4 alkyl, d-C 4 -haloalkyl, Crd alkoxy and Crd haloalkoxy.
  • R 15 , R 16 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, OH, CN, Crd alkyl, Crd alkoxy, C 3 -C 6 alkenyloxy, C 3 -C 6 cycloalkyi, N(R 3 ) 2 , d-d alkylthio, Crd alkylsulphinyl, Crd alkylsulphonyl, phenyl, phenyloxy, benzyl or CO ⁇ 1 , wherein the alkyl, alkoxy, alkenyloxy, cycloalkyi, phenyl and benzyl are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, Crd alkyl, Crd-haloalkyl, Crd alkoxy and Crd haloalkoxy.
  • R 15 , R 16 , R 17 , R 18 and R 19 independently of one another represent hydrogen, d-C 4 alkyl, CN or d-C 4 alkoxy, wherein the alkyl and alkoxy are optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, d-C 4 alkoxy and Crd haloalkoxy.
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a partially or fully unsaturated 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from O, S, N and N(R 3 ), providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, and wherein the ring formed by R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 is optionally substituted by one or more groups, e.g. one to five groups,
  • halogen independently selected from halogen, CN, Crd alkyl, Crd haloalkyi, Crd alkoxy and Crd haloalkoxy.
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from N and N(R 3 ), and wherein the ring formed by R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 is optionally substituted by one or more groups, e.g.
  • one to five groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7- membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from N and N(R 3 ), and wherein the ring formed by R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 is optionally substituted by one or more groups, e.g.
  • one to five groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, d-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7- membered carbocyclic ring wherein the ring formed by R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 is optionally substituted by one or more groups, e.g. one to five groups, independently selected from halogen, CN, Ci-C 4 alkyl, d-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from N and N(R 3 ), and wherein the ring formed by Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 is optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, d-C 4 alkyl, d-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy;
  • each R 1 independently of one another represents hydrogen, d-C 8 alkyl, Ci-C 8 haloalkyl, C 3 -C 8 alkenyl, C 3 -C 8 haloalkenyl, C 3 -C 8 alkynyl, C 3 -C 8 haloalkynyl, phenyl, benzyl or pyridyl, wherein the phenyl, benzyl and pyridyl are optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, d-C 4 alkyl, Ci-C 4 -haloalkyl, Ci-C 4 alkoxy and d-C 4 haloalkoxy; each R 2 independently of one another represents hydrogen, d-C 8 alkyl, Ci-C 8 alkenyl or Ci-Ce haloalkyl;
  • each R 3 independently of one another represents hydrogen, d-C 8 alkyl or COR 4 ;
  • radicals R 3 wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • X represents X-3 or X-5;
  • each R 7 and R 8 independently of one another represent hydrogen, halogen, CN, OH, d- C 4 alkyl or Ci-C 4 haloalkyl;
  • each R 9 and R 10 independently of one another represent hydrogen, halogen, Ci-C 4 alkyl or C1-C4 haloalkyl;
  • each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH,
  • R 11 and R 12 together with the carbon atom to which they are attached may form a C 3 - C 6 cycloalkyi group or a C 3 -C 6 halocycloalkyl group;
  • W represents cycle W-l, W-2, W-3, W-4, W-5, W-6 or W-7;
  • R 15 , R 16 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, CN, OR 1 , Ci-Ce alkyl, C 2 -C 8 alkenyl, C 3 -C 8 cycloalkyi, phenyl, pyridyl, benzyl, N(R 3 ) 2 , C0 2 R 1 , NR 3 COR 2 , SH, Ci-Ce alkylthio, Ci-C 8 alkylsulphinyl, Ci-C 8 alkylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl, wherein the alkyl, alkenyl, cycloalkyi, phenyl, pyridyl and benzyl are optionally substituted by one or more groups independently selected from halogen, CN, OR 1 , d-C 4 alkyl and d-C 4 haloalkyl;
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from N and N(R 3 ), and wherein the ring formed by R 15 and R 18 , R 15 and R , or R and R is optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, d-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, halogen, OR 1 ,
  • CN Ci-C alkyl, C 3 -C 6 cycloalkyl, N(R 3 ) 2 , phenyl, COJR or NR 3 COR 2 , wherein the alkyl, cycloalkyl and phenyl are optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkyl, d-C 4 -haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy; or Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from N and N(R 3 ), and wherein the ring formed by Y 1 and Y 3 , Y 2 and
  • each R 1 independently of one another represents hydrogen, d-C 8 alkyl, Ci-C 8 haloalkyl, C 3 -C 8 alkenyl, C 3 -C 8 haloalkenyl, C 3 -C 8 alkynyl, C 3 -C 8 haloalkynyl, phenyl, benzyl, or pyridyl, wherein the phenyl, benzyl and pyridyl are optionally substituted by one or more groups independently selected from halogen, CN, d-C 4 alkyl, d-C 4 -haloalkyl, d-C 4 alkoxy and Ci-C 4 haloalkoxy;
  • each R 2 independently of one another represents hydrogen, d-C 4 alkyl or Ci-C 4
  • each R 3 independently of one another represents hydrogen or d-C 4 alkyl
  • radicals R 3 wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • X represents X-3
  • each R 7 and R 8 independently of one another represent hydrogen, halogen, CN, OH, d- C 4 alkyl or Ci-C 4 haloalkyl; each R and R independently of one another represent hydrogen, halogen, Ci-C 4 alkyl or Ci-C 4 haloalkyl;
  • each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH, Ci-C 4 alkyl, Ci-C 4 alkoxy, Ci-C 4 haloalkyl or phenyl, wherein the phenyl is optionally substituted by one or more groups independently selected from halogen, CN, methyl, halomethyl, methoxy and halomethoxy;
  • R 11 and R 12 together with the carbon atom to which they are attached may form a Cr C 6 cycloalkyi group or a C 3 -C 6 halocycloalkyl group;
  • Z 3 , Z 4 and Z 5 are substituted only by hydrogen or Z 4 and Z 5 together represent -C ⁇ C-;
  • W represents cycle W-l, W-2 or W-4;
  • R 15 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, OR 1 , CN, Ci-C alkyl, C 3 -C 6 cycloalkyi, N(R 3 ) 2 , C r C alkylthio, C r C alkylsulphinyl, C r C
  • alkylsulphonyl phenyl, benzyl, C0 2 R J or NR 3 COR 2 , wherein the alkyl, cycloalkyi, phenyl and benzyl are optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkyl, Ci-C 4 -haloalkyl, d-C 4 alkoxy and Ci-C 4 haloalkoxy;
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from N and N(R 3 ), and wherein the ring formed by R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 is optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, d-C 4 haloalkyl, d-C 4 alkoxy and d-C 4 haloalkoxy.
  • Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 independently of one another represent hydrogen, halogen, OH,
  • CN Ci-C alkyl, d-C alkoxy, C 3 -C 6 alkenyloxy, C 3 -C 6 cycloalkyi, N(R 3 ) 2 , phenyl or C0 2 R 1 , wherein the alkyl, alkoxy, alkenyloxy, cycloalkyi and phenyl are optionally substituted by one or more groups independently selected from halogen, CN, d-C 4 alkyl, Ci-C 4 -haloalkyl, Ci-C 4 alkoxy and d-C 4 haloalkoxy;
  • Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring wherein the ring formed by Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 is optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy;
  • each R 1 independently of one another represents hydrogen, d-C 4 alkyl or Ci-C 4 haloalkyl; each R 3 independently of one another represents hydrogen or d-C 4 alkyl; wherein when two radicals R 3 are attached to the same nitrogen atom, these radicals can be identical or different;
  • X represents X-3
  • each R 7 and R 8 independently of one another represent hydrogen, halogen, CN, OH, d- C 4 alkyl or Ci-C 4 haloalkyl;
  • each R 9 and R 10 independently of one another represent hydrogen, halogen, methyl or halomethyl
  • each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy or phenyl, wherein the phenyl is optionally substituted by one or more groups independently selected from halogen, CN, methyl, halomethyl, methoxy and halomethoxy;
  • R 11 and R 12 together with the carbon atom to which they are attached may form a C 3 -
  • Z 3 , Z 4 and Z 5 are substituted only by hydrogen or Z 4 and Z 5 together represent -C ⁇ C-;
  • W represents cycle W-l, W-2 or W-4;
  • R 15 , R 17 , R 18 and R 19 independently of one another represent hydrogen, halogen, OH, CN,
  • R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring wherein the ring formed by R 15 and R 18 , R 15 and R 19 , or R 17 and R 18 is optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • G 1 , G 2 and G 3 represent C(R 21 ) 2 , wherein each R 21 independently of one another represents hydrogen or Ci-C 4 alkyl.
  • Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 together with the fragment of the ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring or a 5- to 7-membered heterocyclic ring containing one to three heteroatoms independently selected from O, S, N and N(R 3 ), providing that the heterocycle does not contain adjacent oxygen atoms, adjacent sulphur atoms, or adjacent sulphur and oxygen atoms, and wherein the ring formed by Y 1 and Y 3 , Y 2 and Y 3 , Y 4 and Y 5 , or Y 5 and Y 6 is optionally substituted by one or more groups independently selected from halogen, CN, NH 2 , N0 2 , OH, Ci-C 4 alkyl, CrC 4 haloalkyl, Ci-C 4 alkoxy and Ci-C 4
  • Y 1 and Y 2 independently of one another represent hydrogen, CrC 4 alkyl, CN or d-C 4 alkoxy, wherein the alkyl and alkoxy are optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • Y 1 , Y 2 and Y 3 independently of one another represent hydrogen, CrC 4 alkyl, CN or d-C 4 alkoxy, wherein the alkyl and alkoxy are optionally substituted by one or more groups independently selected from halogen, CN, Ci-C 4 alkoxy and Ci-C 4 haloalkoxy.
  • X represents X-3
  • Z 3 and Z 5 represent methylene
  • each R 9 and R 10 independently of one another represent hydrogen, halogen, methyl or halomethyl
  • each R 11 and R 12 independently of one another represent hydrogen, halogen, CN, OH, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy or phenyl, wherein the phenyl is optionally substituted by one or more groups independently selected from halogen, CN, methyl, halomethyl, methoxy and halomethoxy;
  • R 11 and R 12 together with the carbon atom to which they are attached may form a C 3 - C 6 cycloalkyl group optionally substituted by halogen.
  • D 1 represents N.
  • D 1 represents N
  • D 2 represents C-Y 2 ;
  • D 3 represents N.
  • D 1 represents C-Y 1 ;
  • D 1 represents N
  • D 2 represents C-Y 2 ;
  • D 3 represents C-Y 5 .
  • D 1 represents C-Y 1 ;
  • D 3 represents C-Y 5 .
  • D 1 represents C-Y 1 ;
  • D 2 represents C-Y 2 ;
  • D 1 represents C-Y 1 ;
  • D 2 represents C-Y 2 ;
  • D 3 represents C-Y 5 .
  • the invention provides a compound of formula (VII)
  • R 22 is a halogen and G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y and Y 6 are as defined herein for compounds of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 defined in respect of compounds of formula (I) also apply to compounds of formula (VII).
  • R 22 preferably represents chlorine, bromine or iodine.
  • the invention provides a compound of formula (IX)
  • G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 are as defined herein for a compound of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 defined in respect of compounds of formula (I) also apply to compounds of formula (IX).
  • the invention provides a compound of formula (X)
  • G , G , G , p, X, D , D , D , Y , Y ⁇ and Y are as defined for a compound of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 defined in respect of compounds of formula (I) also apply to compounds of formula (X).
  • the invention provides a compound of formula (XI)
  • G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 are as defined for a compound of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 defined in respect of compounds of formula (I) also apply to compounds of formula (XI).
  • the invention provides a compound of formula (XIII)
  • G 1 , G 2 , G 3 , p, X D 1 , D 2 , D 3 , Y 3 , Y 4 , Y 6 and R 15 are as defined for a compound of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 , Y 6 and R 15 defined in respect of compounds of formula (I) also apply to compounds of formula (XIII).
  • the invention provides a compound of formula (XIV)
  • G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 , Y 6 and R 15 are as defined for a compound of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 , Y 6 and R 15 defined in respect of compounds of formula (I) also apply to compounds of formula (XIV).
  • the invention provides a compound of formula (XX)
  • G 1 , G 2 , G 3 , p, D 3 , Y 4 and Y 6 are as defined herein for a compound of formula (I) and X' represents X'-l, X'-2 or X'-3: # Z 2 — # #— z-— z-— # # # _ Z US_ Z U_ Z 12_ #
  • G 1 , G 2 , G 3 , p, Y 4 and Y 6 are as defined for a compound of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, Y 4 and Y 6 defined in respect of compounds of formula (I) also apply to compounds of formula (Ilia).
  • G 1 , G 2 , G 3 , p, Y 4 and Y 6 are as defined for a compound of formula (I) and R 38 represents hydrogen, CO-CH 3 , CO-CH 2 CH 3 , CO-CH 2 CH 2 CH 3 , CO-CH(CH 3 ) 2 , CO-CF 3 or CO- CF 2 CF 3 ; or a salt or N-oxide thereof.
  • R 38 represents hydrogen, CO-CH 3 , CO-CH 2 CH 3 , CO-CH 2 CH 2 CH 3 , CO-CH(CH 3 ) 2 , CO-CF 3 or CO- CF 2 CF 3 ; or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, Y 4 and Y 6 defined in respect of compounds of formula (I) also apply to compounds of formula
  • G 1 , G 2 , G 3 , p, Y 4 and Y 6 are as defined for a compound of formula (I); or a salt or N-oxide thereof.
  • the preferred definitions of G 1 , G 2 , G 3 , p, Y 4 and Y 6 defined in respect of compounds of formula (I) also apply to compounds of formula (Via).
  • the compounds of formula (I) may exist as different geometric or optical isomers or in different tautomeric forms. These may be separated and isolated by well-known (usually chromatographic) techniques, and all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms, such as deuterated compounds, are part of the present invention.
  • the carbon-nitrogen double bonds of the compound of formula (I) allow the cis/trans isomers shown below:
  • the present invention includes each of these isomers.
  • the invention may provide a compound of formula (I) as just one of these isomers or as a mixture of one or more isomers in any ratio.
  • the invention also includes the corresponding isomers of the intermediates described herein, in particular compounds (VII), (IX), (X), (XI), (XIII) and (XIV).
  • VII compounds
  • IX compounds
  • X compounds
  • XIII XIII
  • XIV synthesis of the other geometric isomers where possible.
  • reaction scheme A shown below also encompasses reaction scheme B:
  • Table X represents Table 1 (when X is 1), Table 2 (when X is 2), Table 3 (when X is 3), Table 4 (when X is 4), Table 5 (when X is 5), Table 6 (when X is 6), Table 7 (when X is 7), Table 8 (when X is 8), Table 9 (when X is 9), Table 10 (when X is 10), Table 11 (when X is 11), Table 12 (when X is 12), Table 13 (when X is 13), Table 14 (when X is 14) and Table 15 (when X is 15), Table 16 (when X is 16), Table 17 (when X is 17), Table 18 (when X is 18), Table 19 (when X is 19), Table 20 (when X is 20), Table 21 (when X is 21), Table 22 (when X is 22), Table 23 (when X is 23), Table 24 (when X is 24), Table 25 (when X is 25), Table 26 (when X is 26), Table 27 (when X is 27), Table 28 (when X
  • Table 1 This table discloses compounds 1.001 to 1.479 of the formula (I-I)
  • Table 6 This table discloses compounds 6.001 to 6.479 of the formula (I-VI)
  • Table 8 This table discloses compounds 8.001 to 8.479 of the formula (I-VIII)
  • Table 10 This table discloses compounds 10.001 to 10.479 of the formula (I-X)
  • Table 14 This table discloses compounds 14.001 to 14.479 of the formula (I-XIV)
  • Table 18 This table discloses compounds 18.001 to 18.479 of the formula (I-XVIII)
  • Table 24 This table discloses compounds 24.001 to 24.479 of the formula (I-XXIV)
  • Table 26 This table discloses compounds 26.001 to 26.479 of the formula (I-XXVI) I)
  • Table 30 This table discloses compounds 30.001 to 30.479 of the formula (I-XXX)
  • Table 34 This table discloses compounds 34.001 to 34.479 of the formula (I-XXXIV)
  • Table 38 illustrates embodiments E of compounds of formula (I-XXXVIII) (I-XXXVIII)
  • the compounds in table 39 illustrate compounds of formula (I-XXXVIII) wherein E is as defined in table 38.
  • the compounds in Tables 1 to 37 and table 39 include all isomers, tautomers and mixtures thereof, including the cis/trans isomers shown above.
  • the compounds of the invention may be made by a variety of methods, illustrated in schemes 1-17.
  • the compounds depicted in the schemes also indicate any isomers and tautomers, in particular the geometric isomers arising from the oxime and oxime ether moieties.
  • Compounds of formula (I) may be prepared by reacting a compound of formula (II), wherein X, D 1 , D 2 , Y 3 and W are as defined herein for compounds of formula (I), with a compound of formula (III), wherein G 1 , G 2 , G 3 , D 3 , Y 4 , Y 6 and p are as defined herein for compounds of formula (I), and T 1 and T 2 are Ci-C 8 alkoxy, or T 1 and T 2 together with the carbon they are attached to form a carbonyl group or a ketal function of the form C(0-d-C 6 - alkylidene-O) whereby the alkylidene fragment may optionally be mono- to tetra-substituted by Ci-C 6 alkyl, as seen in scheme 1.
  • X'-1 X'-2 X'-3 may be prepared by catalytic hydrogenation from compounds of formula (la), that is a compound of formula (I) wherein Z and Z 5 , Z 8 and Z 9 or Z 13 and Z 14 together form a ethynyl group and X' is defined as herein for compounds of formula (lb), in the presence of a metal catalyst, for example palladium, nickel or platinum.
  • a metal catalyst for example palladium, nickel or platinum.
  • the reaction is usually carried out in the presence of a solvent under a hydrogen atmosphere. In some cases it is necessary to apply pressure in the range of 1 to 100 bar.
  • Suitable solvents for such reactions are alcohols, such as methanol or ethanol, cyclic ethers, such as dioxane or tetrahydrofuran or esters like ethyl acetate.
  • the reaction is usually carried out at a reaction temperature ranging from 0°C to the boiling point of the solvent.
  • Examples for the hydrogenation in the presence of a nickel catalyst can be found in Journal of Organometallic Chemistry, 333(2), 139-53; 1987.
  • Examples for the hydrogenation in the presence of a palladium catalyst can be found in Tetrahedron, 63(26), 6015-6034; 2007 or in Bioorganic & Medicinal Chemistry, 9(11), 2863- 2870; 2001.
  • Examples for the hydrogenation in the presence of a platinum catalyst can be found in Journal of Organic Chemistry, 53(2), 386-90; 1988 or in Journal of Medicinal Chemistry, 32(8), 1820-35; 1989
  • X'-1 X'-2 X'-3 and each R 7 and R 8 independently of one another represent hydrogen, halogen, Ci-C 4 alkyl, Ci-C 4 haloalkyi, phenyl or CN, wherein phenyl is optionally substituted by one or more groups, e.g.
  • a metal catalyst for example palladium, nickel or platinum.
  • the reaction is usually carried out in the presence of a solvent under a hydrogen atmosphere.
  • Suitable solvents for such reactions are alcohols, such as methanol or ethanol, cyclic ethers, such as dioxane or tetrahydrofuran or esters like ethyl acetate.
  • the reaction is usually carried out at a reaction temperature ranging from 0°C to the boiling point of the solvent.
  • Examples for the hydrogenation in the presence of a nickel catalyst can be found in Journal of Organic Chemistry, 69(6), 1959-1966; 2004.
  • Examples for the hydrogenation in the presence of a palladium catalyst can be found in Journal of Organic Chemistry, 74(16), 6072-6076; 2009.
  • Examples for hydrogenation in the presence of a platinum catalyst can be found in Organometallics, 5(2), 348-55; 1986.
  • X"-2 X"-3 X"-4 may be obtained from compounds of (Ie), that is a compound of formula (I) wherein Z 5 , Z 9 or Z 14 represent a carbonyl group and X" is as defined for compounds of formula (If)
  • the Wittig reaction comprises the reaction between an aldehyde or a ketone, for example the ketone of formula (Ie) and a phosphorous ylide.
  • Phosphorous ylides are usually prepared by treatment of a phosphonium salt with a base and phosphonium salts are usually prepared from a triarylphosphine and an alkyl halide.
  • Several improvements and modification of the Wittig reaction are known and are described for example in March's Advanced Organic Chemistry: Reaction, Mechanisms and Structure, Sixth Edition, 2007 and references therein. Specific reaction conditions may be found in Journal of the American Chemical Society, 131(34), 12344-12353; 2009; Journal of Medicinal Chemistry, 51(22), 7193-7204; 2008 or Journal of Organic Chemistry, 74(11), 4166-4176; 2009.
  • compounds of formula (I) may be prepared by reacting compounds of formula (V) wherein X, D 1 , D 2 , Y 3 , and W are as defined herein for compounds of formula (I) and R 23 is a halogen, in particular chlorine, bromine or iodine, or a sulfonic acid ester group, such as mesylate, tosylate, triflate, a phenylsulfonic acid ester, a nitro-phenylsulfonic acid ester, or a nonafluorobutylsulfonic acid ester, and a compound of formula (VI) wherein G 1 , G 2 , G 3 , D 3 , Y 4 , Y 6 and p are as defined herein for compounds of formula (I).
  • compounds of formula (I) may be prepared by reacting compounds of formula (VII) wherein G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 are as defined herein for compounds of formula (I) and R 22 is a halogen, in particular chlorine, bromine or iodine, with a compound of formula (VIII) wherein W is as defined herein for compounds of formula (I) and M is an organometallic residue.
  • This can be done using one of several techniques well known to the person skilled in the art, including Suzuki, Stille and Negishi cross coupling reactions.
  • Examples and specific conditions for the Stille reaction may be found in Bioorganic & Medicinal Chemistry Letters, 19(19), 5689-5692; 2009; Journal of Organic Chemistry, 73(12), 4491-4495; 2008; Journal of the American Chemical Society, 129(3), 490-491; 2007 or in Journal of Organic Chemistry, 75(2), 424-433; 2010.
  • Examples and specific conditions for the Negishi reaction may be found in European Journal of Inorganic Chemistry, (26), 4101-4110; 2008; Tetrahedron Letters, 50(38), 5329-5331; 2009; Tetrahedron Letters, 51(2), 357-359; 2010 or in Tetrahedron Letters, 51(19), 2657- 2659; 2010.
  • Examples and specific conditions for the Suzuki reaction may be found in
  • Compounds of formula (Ig), that is a compound of formula (I) wherein W is W-2, may be obtained from amidines of formula (X) wherein G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 are as defined herein for compounds of formula (I).
  • amidines of formula (X) wherein G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 are as defined herein for compounds of formula (I).
  • Such transformations can be effected using a number of conditions well known to the person skilled in the art.
  • Amidines of formula (X) may be prepared from nitriles of formula (IX) wherein G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y and Y 6 are as defined herein for compounds of formula (I). Typical conditions for such transformations can be found in Bioorganic & Medicinal
  • Compounds of formula (XIV) may be prepared by oxidation from compounds of formula (XIII), wherein G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 , Y 6 and R 15 are as defined herein for compounds of formula (I).
  • Such oxidations can be effected using a number of conditions well known to the person skilled in the art. Specific reaction conditions may be found in Journal of the American Chemical Society, 132(8), 2532-2533; 2010; Journal of Organic Chemistry, 74(15), 5750-5753; 2009 or in Tetrahedron, 64(29), 7008-7014; 2008.
  • Compounds of formula (XIII) may be prepared from aldehydes of formula (XI) wherein G 1 , G 2 , G 3 , p, X, D 1 , D 2 , D 3 , Y 3 , Y 4 and Y 6 are as defined herein for compounds of formula (I) and compounds of formula (XII) wherein R 15 is as defined herein for compounds of formula (I).
  • Typical conditions for such transformations can be found in Tetrahedron, 64(29), 7008-7014; 2008; Journal of Organic Chemistry, 72(20), 7783-7786; 2007 or in Organic Letters, 9(6), 1169-1171; 2007.
  • Compounds of formula (Ila), that is a compound of formula (II) wherein Z and Z 5 , Z 8 and Z 9 or Z 13 and Z 14 are both methylene and X' is as defined for compounds of formula (la) may be obtained from compounds of (XVIII) wherein D 1 , D 2 , Y 3 and W are as defined herein for a compound of formula (I) and X' is as herein defined for a compound of formula (la) by cleavage of the phtalimide protecting group. Examples for such deprotections can be found in Greene, T. W., Wuts, P. G. N., Protective Groups in Organic Synthesis, John Wiley & Sons, Inc, 2006.
  • Compounds of formula (XVII) may be prepared from compounds of formula (XVI) wherein D 1 , D 2 , Y 3 and W are as defined herein for a compound of formula (I) and X' is as herein defined for a compound of formula (la) by a Mitsunobu reaction.
  • the Mitsunobu reaction comprises the substitution of primary or secondary alcohols with nucleophiles like for example N-hydroxyphtalimide as seen in Scheme 9, in the presence of a dialkyl azodicarboxylate and a trialkyi- or triaryl phosphine.
  • Compounds of formula (la) may be prepared from compounds of formula (VI) wherein G 1 , G 2 , G 3 , p, D 3 , Y 4 and Y 6 are as defined herein for compounds of formula (I) and compounds of formula (Va), that is a compound of formula (V) wherein Z and Z 5 , Z 8 and Z 9 or Z 13 and Z 14 together form an ethynyl group and X' is as defined herein for a compound of formula (la).
  • the alkylation reaction can be carried out analogously to procedure 5 as shown in Scheme 5.
  • compounds of (la) can be prepared by a Sonogashira reaction of compounds of formula (XXI) wherein D 1 , D 2 , Y 3 and W are as defined herein for compounds of formula (I) and R is as defined herein for a compound of formula (VII) with compounds of formula (XX) wherein G 1 , G 2 , G 3 , p, D 3 , Y 4 and Y 6 are as defined herein for a compound of formula (I) and X' is as defined for a compound of formula (la) .
  • the reaction can be carried out in the presence of a palladium catalyst like tetrakis triphenyphosphine or dichlorobis (triphenylphosphine) palladium(II), a copper(I) salt like copper (I)chloride, copper(I)bromide or copper(I)iodide and a base, for example
  • a palladium catalyst like tetrakis triphenyphosphine or dichlorobis (triphenylphosphine) palladium(II)
  • a copper(I) salt like copper (I)chloride, copper(I)bromide or copper(I)iodide
  • a base for example
  • the base may also serve as solvent.
  • suitable solvents are N,N-dimethylformamide, ⁇ , ⁇ -dimethylacetamide, acetonitrile, dimethylsulfoxide, dioxane or tetrahydrofuran.
  • the reaction is usually carried out at a reaction temperature ranging from 0°C to the boiling point of the solvent. Examples for Sonogashira reactions can be found in Handbook of Organopalladium Chemistry for Organic Synthesis 2002, 1, 493- 529.
  • the reaction can be carried out in the presence of a palladium catalyst like tetrakis triphenyphosphin or dichlorobis (tri phenyl phosphine) palladium(II), a copper(I) salt like copper (I)chloride; copper(I)bromide or copper(I)iodide and a base, for example triethylamine, ethyl-diisopropyl-amine, diethyl -a mine, diisopropyl-amine or dicyclohexyl- amine. Where possible, the base may also serve as solvent.
  • a palladium catalyst like tetrakis triphenyphosphin or dichlorobis (tri phenyl phosphine) palladium(II), a copper(I) salt like copper (I)chloride; copper(I)bromide or copper(I)iodide and a base, for example triethylamine, ethyl-di
  • Examples for other suitable solvents are N,N-dimethylformamide, ⁇ , ⁇ -dimethylacetamide, acetonitrile, dimethylsulfoxide, dioxane or tetrahydrofuran.
  • the reaction is usually carried out at a reaction temperature ranging from 0°C to the boiling point of the solvent.
  • Examples for Sonogashira reactions can be found in Handbook of Organopalladium Chemistry for Organic Synthesis 2002,1, 493-529.
  • Compounds of formula (XXX) may be prepared from compounds of formula (XXIX) wherein D 1 , D 2 ,Y 3 and W are as defined herein for compounds of formula (I), R 7 and R 8 are as defined herein for compounds of formula (Ic) and R 24 represents Ci-C 4 alkyl, by reduction with a metal hydride, for example lithium aluminium hydride or diisobutyl aluminium hydride. Examples for such reductions can found in Journal of Combinatorial Chemistry, 7(6), 958- 967; 2005. The reaction is usually carried out at temperatures between -100 to 20°C in the presence of a solvent.
  • a metal hydride for example lithium aluminium hydride or diisobutyl aluminium hydride. Examples for such reductions can found in Journal of Combinatorial Chemistry, 7(6), 958- 967; 2005.
  • the reaction is usually carried out at temperatures between -100 to 20°C in the presence of a solvent.
  • Appropriate bases are for example metal hydrides like calcium-, lithium, sodium or potassium hydride, organometal compounds like buthyllithium or organic bases like for example triethyl-amine or ethyl-diisopropyl-amine in combination with lithium chloride. Examples can be found in Bioorganic & Medicinal Chemistry, 11(18), 4015-4026; 2003; Synthesis, (4), 283-5; 1981 or in Journal of Medicinal Chemistry, 53(3), 1200-1210; 2010
  • Z 1 , Z 3 , Z 4 , Z 6 , Z 7 , Z 8 , Z 10 , Z 11 , Z 12 and Z 13 are as defined herein for compounds of formula (I) may be prepared from aldehydes of formula (XXXIII), wherein G 1 , G 2 , G 3 , p, D 3 , Y 4 and Y 6 are as defined for compounds of formula (I) and X'" is as defined for a compound of formula (Ik), and compounds of formula (XXIa), that is a compound of formula (XXI) wherein R 22 is R 22 , wherein R 22' is chlorine, bromine or iodine.
  • Such a transformation can be done by the halogen metal exchange in compound (XXIa) with an appropriate reagent like for example magnesium, isopropyl magnesium chloride or bromide or n-buthyllithium and the reaction of this metalated pyridine intermediate with a compound of formula (XXXIII).
  • an appropriate reagent like for example magnesium, isopropyl magnesium chloride or bromide or n-buthyllithium
  • Oximes of formula (VI) may be obtained by a condensation reaction, whereby a compound of formula (III), wherein G 1 , G 2 , G 3 , p, D 3 , Y 4 and Y 6 are as defined herein for compounds of formula (I) and T 1 and T 2 are Ci-C 8 alkoxy, or T 1 and T 2 together with the carbon they are attached to form a carbonyl group or a ketal function of the form C(0-d-C 6 - alkylidene-O) whereby the alkylidene fragment may optionally be mono- to tetra-substituted by Ci-C 6 -alkyl, is reacted with hydroxylamine, or, alternatively, with a salt of hydroxylamine.
  • condensation processes is given below.
  • ketones of formula (Illb), that is a compound of formula (III) wherein D 3 is N and Y 6 is hydrogen may be obtained from compounds of formula (XXXIVb), wherein G 1 , G 2 , G 3 , Y 4 and p are as described herein for compounds of formula (I) and R 38 represents hydrogen, CO-CH 3 , CO-CH 2 CH 3 , CO-CH 2 CH 2 CH 3 , CO-CH(CH 3 ) 2 , CO-CF 3 , CO-CF 2 CF 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 or CH(CH 3 ) 2 using acidic hydrolysis methods well known to the person skilled in the art.
  • Enol ethers of formula (XXXIVb) can be obtained by reacting enaminones of formula
  • Enaminones of formula (XXXVI) can be obtained by reacting ketones of formula (XXXVIII) wherein G 1 , G 2 , G 3 and p are as described herein for compounds of formula (I) and R 38 represents hydrogen, CO-CH 3 , CO-CH 2 CH 3 , CO-CH 2 CH 2 CH 3 , CO-CH(CH 3 ) 2 , CO-CF 3 , CO- CF2CF3, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 or CH(CH 3 ) 2 with ⁇ , ⁇ -dimethylformamide dialkyl acetals of formula (XXXVII) wherein R 39 represents C1-C4 alkyl.
  • Such condensation reactions are well known to the person skilled in the art.
  • the reaction is carried out in an inert solvent or without solvent at temperatures ranging from 0°C to 250°C preferably between 50 and 160°C.
  • Specific reaction conditions may be found in Synthesis, (97), 3397, 1964; Synthesis, (97), 3407, 1964; Journal of Med. Chem., Vol. 52, No. 16, 5152-5163; Tetrahedron Lett, (27), 2567, 1986; Tetrahedron Lett, (50), 2255-2264, 1994; Synthetic Commun., (28), 10, 1743-1753, 1998 or in Chem. Ber., (104), 2975, 1971.
  • Enol ethers of formula (XXXVIII) can be obtained by reacting ketones of formula (XXXX) wherein G 1 , G 2 , G 3 and p are as described herein for compounds of formula (I) with an alcohol of formula (XXXIX) wherein R 38 represents hydrogen, CO-CH 3 , CO-CH 2 CH 3 , CO- CH 2 CH 2 CH 3 , CO-CH(CH 3 ) 2 , CO-CF 3 , CO-CF 2 CF 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 or CH(CH 3 ) 2 .
  • Such reactions can be affected using a number of conditions well known to the person skilled in the art. Specific reaction conditions may be found in W02004104007.
  • oximes of formula (VI) can be obtained by a nitrosation reaction of compounds of formula (XXXV), wherein G 1 , G 2 , G 3 , p, D 3 , Y 4 and Y 6 are as defined herein for compounds of formula (I), with base and an alkyl nitrite, as seen in scheme 17.
  • Typical bases include lithium diisopropyl amide (LDA), lithium hexamethyldisilazane, n-butyl lithium, s-butyl lithium, tert-butyl lithium, sodium tert-butylate or potassium tert-butylate .
  • Typical alkyl nitrites include isopentyl nitrite and tert-butyl nitrite.
  • the compound of formula (XXXIV), the alkyl nitrite or the base can be used in different stoichiometric amounts, with each reagent possibly being in excess with respect to the others.
  • such reactions are carried out under non-aqueous conditions in an inert solvent such as hexane, heptanes, cyclohexane, toluene or ethers such as THF or tert-butyl methyl ether.
  • the reaction may be performed at temperatures ranging from -80 to 250°C, preferably between -50 and 120°C.
  • Such reactions can lead to a mixture of the E- and the Z-oxime (ether) product, or the product may also be exclusively either the E- or the Z-oxime (ether).
  • the reaction may be performed in the presence or absence of an inert organic or inorganic solvent, or in the presence of a mixture of such solvents. Preferentially, it is performed in the presence of one or more solvents.
  • Preferred solvents include the following aliphatic or aromatic hydrocarbons, which may optionally be substituted by one or more halogen atoms, such as pentane, hexanes, heptanes, cyclohexane, petroleum ether, benzene, toluene, xylene, chlorobenzene, dichlorobenzenes, dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride, ethers such as diethylether, diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane or diglycol dimethyl ether, ketones such as acetone
  • solvents includes water and alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, tert-butanol, pentanol, isopentanol, hexanol, thfluorethanol, ethylene glycol or methoxyethanol.
  • alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, tert-butanol, pentanol, isopentanol, hexanol, thfluorethanol, ethylene glycol or methoxyethanol.
  • the reaction may be performed between -20 C and 250 C, preferentially between 0 ° C and lOO C. In some cases the reaction mixture may be heated to reflux.
  • compounds can be used in the form of the free compound, or, alternatively, they can be used in the form of a salt such as the acetate, trifluoroacetate, propionate, benzoate, oxalate, methyl solfonate, phenylsulfonate, p-tolylsulfonate, trifluormethylsulfonate, fluoride, chloride, bromide, iodide, sulfate, hydrogensulfate or nitrate, including bis-salts if appropriate.
  • the reaction can be carried out in the absence of an acid using the free compounds. Alternatively, the reaction may be performed in the presence of an acid in catalytic, stoichiometric or excess amounts.
  • Acids that could be used include acetic acid, propionic acid, oxalic acid, trifluoroacetic acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, methansulfonic acid, para-toluenesulfonic acid, sulphuric acid, sodium hydrogensulfate and phosphoric acid.
  • the reaction can optionally be carried out in a water-free solvent system in the presence of a drying agent, such as sodium or magnesium sulfate, potassium carbonate or molecular sieves.
  • the condensation reaction can lead to a mixture of the E- and the Z-oxime (ether) product.
  • the condensation product may also be exclusively either the E- or the Z- oxime (ether).
  • Condensations can be performed under reduced pressure, normal pressure or increased pressure. Preferentially the reaction is performed under normal pressure.
  • the reaction may be performed in the absence or presence of a solvent or a mixture of solvents.
  • Preferential solvents include the following aliphatic or aromatic hydrocarbons that may optionally be substituted by one or more halogen atoms such as pentane, hexanes, heptanes, cyclohexane, petroleum ether, benzene, toluene, xylene, chlorobenzene, dichlorobenzenes, dichloromethane, chloroform, 1,2-dichloroethanev or carbon tetrachloride, ethers such as diethyl ether, diisopropyl ether, tert-butyl-methyl ether, tetrahydrofuran, 1,4- dioxane, dimethoxyethane or diglycol dimethyl ether, ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone or methyl isobutyl
  • the selction of solvents includes also water and alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, tert-butanol, pentanol, isopentanol, hexanol, trifluorethanol, ethylene glycol or methoxyethanol.
  • the reaction may be performed in a biphasic system comprising an organic solvent that is not miscible with water, such as toluene, dichloromethane, dichloro-ethylene, and an aqueous solvent, such as water.
  • a phase-transfer catalyst such as tetra-n-butylammonium bromide (TBAB)
  • TDMBAC Tetradecyldimethylbenzylammonium chloride
  • N-Benzyltrimethylammonium hydroxide N-Benzyltrimethylammonium hydroxide
  • the biphasic reaction may be performed with or without ultrasonication.
  • the reaction may be carried out at temperatures varying from -100°C and 250°C. Preferentially, the temperature range is between 0°C and 100°C.
  • an organic or inorganic base may be present such as alkali- and earth alkali acetates, amides, carbonates, hydrogencarbonates, hydrides, hydroxides or alcoholates such as sodium, potassium, caesium or calcium acetate, sodium, potassium, caesium or calcium carbonate, sodium, potassium, caesium or calcium hydrogencarbonate, sodium, potassium, caesium or calcium hydride, sodium, potassium, caesium or calcium amide, sodium, potassium, caesium or calcium hydroxide, sodium, potassium, caesium or calcium methanolate, sodium, potassium, caesium or calcium ethanolate, sodium, potassium, caesium or calcium n-, i-, s- or t-butanolate, triethylamine, tri propylamine, tributylamine, di- isopropyl-ethylamine, ⁇ , ⁇ -dimethyl-cyclohexylamine, N-methyl-dicyclohexyl
  • the alkylation can be performed under reduced pressure, normal pressure or increased pressure. Preferentially the reaction is performed under normal pressure.
  • schemes 1) to 16 may be required to be purified using, for example, chromatography, crystallisation or other purification techniques well known to the person skilled in the art.
  • the compounds of formula (I) to formula (XXXIII) 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 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, 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).
  • Fungi imperfecti e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria
  • Basidiomycetes e.g. Rhizoctonia, Hemileia, Puccinia
  • 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 (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides like bromoxynil or classes of herbicides
  • EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors
  • GS glutamine synthetase
  • PPO protoporphyrinogen-oxidase
  • imazamox by conventional methods of breeding (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 ® .
  • useful plants is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
  • YieldGard ® (maize variety that expresses a CrylA(b) toxin); YieldGard Rootworm ® (maize variety that expresses a CrylllB(bl) toxin); YieldGard Plus ® (maize variety that expresses a CrylA(b) and a CrylllB(bl) toxin); Starlink ® (maize variety that expresses a Cry9(c) toxin); Herculex I ® (maize variety that expresses a CryIF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B ® (cotton variety that expresses a CrylA(c) toxin); Bollgard I ® (cotton variety that expresses a CrylA(c) toxin); Bollgard II
  • 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 active 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.
  • 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 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 active 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 active 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) may 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, 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).
  • the agrochemical formulations will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula (I), 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.
  • 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.
  • 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) 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) 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 composition comprising as an active ingredient a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a
  • 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 A. 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 prolificans.
  • Microsporum Spp Trichophyton Spp, Epidermophyton Spp, Mucor Spp, Sporothorix Spp, Phialophora Spp, Cladosporium Spp, Petriellidium spp, Paracoccidioides Spp and Histoplasma Spp.
  • compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
  • the present invention provides a fungicidal composition
  • a fungicidal composition comprising a fungicidally effective amount of a compound of formula (I), optionally comprising at least one additional active ingredient.
  • 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 1-37, 39 and 41-42) 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 examples 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,
  • Carbamates including aryl carbamates, such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl;
  • Benzoyl ureas such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or chlorfluazuron;
  • Organic tin compounds such as cyhexatin, fenbutatin oxide or azocyclotin;
  • Macrolides such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, or spinosad, spinetoram or azadirachtin;
  • 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 1-37, 39 and 41-42, 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
  • 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-/V-methyl-/V-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 [CC
  • bromopropylate (94) + TX, buprofezin (99) + TX, butocarboxim (103) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, calcium polysulfide (IUPAC name) (111) + TX, camphechlor (941) + TX, carbanolate (943) + TX, carbaryl (115) + TX, carbofuran (118) + TX, carbophenothion (947) + TX, CGA 50'439 (development code) (125) + TX, chinomethionat (126) + TX, chlorbenside (959) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorfenapyr (130) + TX, chlorfenethol (968) + TX, chlorfenson (970) + TX, chlorfensulphide (971) + TX, chlorfen
  • fenothiocarb (337) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fen- pyroximate (345) + TX, fenson (1157) + TX, fentrifanil (1161) + TX, fenvalerate (349) + TX, fipronil (354) + TX, fluacrypyrim (360) + TX, fluazuron (1166) + TX, flubenzimine (1167) + TX, flucycloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1169) + TX, flufenoxuron (370) + TX, flumethrin (372) + TX, fluorbenside (1174) + TX, fluvalinate (1184) + TX, FMC 1137 (development code) (1185) + TX, formetanate (405) + TX, forme
  • an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX;
  • an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX; an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1122)
  • a bactericide selected from the group of substances consisting of l-hydroxy-l/-/-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) + T
  • 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
  • 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
  • an insect pheromone selected from the group of substances consisting of (£)-dec-5-en- 1-yl acetate with (f)-dec-5-en-l-ol (IUPAC name) (222) + TX, (£)-tridec-4-en-l-yl acetate (IUPAC name) (829) + TX, (f)-6-methylhept-2-en-4-ol (IUPAC name) (541) + TX, (E,Z)- tetradeca-4,10-dien-l-yl acetate (IUPAC name) (779) + TX, (Z)-dodec-7-en-l-yl acetate
  • 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-dichlorophenyl)ethyl acetate (IUPAC name) (1451) + TX, 2,2-dichlorovinyl 2- ethylsulphinylethyl methyl phosphate (IUPAC name) (1066) + T
  • 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, cloth
  • flubendiamide (CAS. Reg. No.: 272451-65-7) + TX, flucofuron (1168) + TX, flucycloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1169) + TX, flufenerim [CCN] + TX, flufenoxuron (370) + TX, flufenprox (1171) + TX, 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,
  • 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) + T
  • 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-isopentenylaminopur
  • a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX;
  • a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX;
  • a rodenticide selected from the group of substances consisting of 2-isovalerylindan-l,3- dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (
  • 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,
  • a virucide selected from the group of substances consisting of imanin (alternative name)
  • 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 [35554-44-0] + TX, imibenconazole [86598- 92-7] + 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-
  • 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 under the internet address http://www.alanwood.net/pesticides/ [A. Wood; Compendium of Pesticide Common Names, Copyright ⁇ 1995-2012]; or preferably one of the further pesticides listed below.
  • the compound of the formula I is preferably a compound selected from the Tables 1-37, 39 and 41-42; more preferably a compound selected from the Tables 41 and 42;
  • the mixing ratios can vary over a large range and are, preferably 100: 1 to 1:6000, especially 50: 1 to 1:50, more especially 20: 1 to 1:20, even more especially 10: 1 to 1: 10.
  • Those mixing ratios are understood to include, on the one hand, ratios by weight and also, on other hand, molar ratios.
  • mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient” relates to the respective mixture of TX with the mixing partner).
  • Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type.
  • other formulation types may be prepared.
  • one active ingredient is a water insoluble solid and the other a water insoluble liquid
  • the resultant composition is a suspoemulsion (SE) formulation.
  • the mixtures comprising a TX selected from Tables 1-37, 39 and 41-42 and one or more active ingredients as described above can be applied, for example, in a single "ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix", and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days.
  • the order of applying the compounds of formula I selected from Tables 1-37, 39 and 41-42 and the active ingredients as described above is not essential for working the present invention.
  • 6-bromo-pyridin-2-carboxylic acid (15.4g) and a catalytic amount of DMF in dichloromethane (150ml_) was added dropwise oxalyl chloride (11.6g).
  • the reaction mixture was stirred for 30min at room temperature and 30min at reflux and then concentrated to give 6-bromo-pyridine-2-carboxylic acid chloride as a beige solid, which was dissolved in dichloromethane (80ml_) and added dropwise to a solution of (Z)-4-amino-pent-3-en-2-one (7.6g) in dichloromethane (70ml_) and triethylamine (9.3g) at -20°C.
  • 6-Methyl-pyridine-2-carboxamidine hydrochloride 25 g was added portionwise to a stirred sodium ethoxide solution, prepared from ethanol (500 mL) and metallic sodium (3.05 g) at room temperature, followed by dropwise addition of ethyl -3-oxobutanoate (16.6 mL).
  • the reaction mixture (beige suspension) was stirred for 3.5 hours at reflux. Then, the solvent was removed in vacuo. Wwater and 1M HCI was added until the reaction mixture reached pH 3, followed by extraction with ethyl acetate. The organic fraction was dried over sodium sulfate. Filtration and concentration gave 6-methyl-2-(6-methyl-pyridin-2-yl)- pyrimidin-4-ol (13.1 g) as a beige solid.
  • Step B) A 50 mL single-necked round-bottom flask equipped with a condenser was charged with a solution of 2-methyl-5,6,7,8-tetrahydro-quinolin-4-ol (4.00 g) in phosphorus oxide chloride (18.3 ml.) under an argon atmosphere. The resulting colourless solution was stirred at 100°C for 3.5 hours, after which time TLC indicated that no starting material was remaining. The solvent was removed in vacuo and hot water (40-50°C) was added carefully and slowly to the residue to hydrolyse the remaining phosphorus oxide chloride. Under cooling with an ice-water cooling bath, the pH was adjusted to 12 by the addition of 4 M aqueous NaOH.
  • Step C A 25 ml. single-necked round-bottom flask equipped with a condenser was charged with a solution of 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline (560 mg) in acetic anhydride (0.49 ml_). Under stirring, benzaldehyde (0.34 ml.) was added and the resulting yellow solution was stirred under heating to reflux for 3.5 hours. Following the course of the reaction by TLC indicated that starting material was consumed by this time. The resulting brown solution was cooled to room temperature. Crushed ice was added and the pH was adjusted to 10 using a small amount of 2 M aqueous NaOH.
  • Step D A 25 mL single-necked round-bottom flask was charged with a solution of 8- benzylidene-4-chloro-2-methyl-5,6,7,8-tetrahydro-quinoline (263 mg) in dichloromethane (2.0 mL) / methanol (3.8 mL). Under stirring and cooling to -78°C with a dry ice-acetone cooling bath, ozone was passed through the reaction mixture for 3 minutes until a light blue color was observed. Then dimethyl sulfide (2.0 mL) was added at -78°C Then, the reaction mixture was allowed to reach room temperature and was stirred for 4 hours.
  • Step A) A 5 ml. microwave tube was charged with a solution of 4-chloro-2-methyl- 5,6,7,8-tetrahydroquinoline (500 mg) in 1,2-dichloroethane (2.50 ml_). Under stirring, trimethylboroxine (380 mg), potassium carbonate (647 mg) and dichloro[l,l'- bis(di phenyl phosphino)ferrocene] palladium(II) dichloromethane adduct (101 mg) were added and the resulting red suspension was degassed under argon for 5 minutes. The reaction mixture was subjected to microwave irradiation at 120°C for 0.5 hour.
  • TLC Plates: Merck DC-Plates, silica gel F 254 , saturated atmosphere in developing tank,
  • Step C A 25 mL single-necked round-bottom flask equipped with a condenser was charged with a solution of 2,4-dimethyl-5,6,7,8-tetrahydro-quinoline-l-oxide (334 mg) in dichloromethane (2.00 mL) under an argon atmosphere. Under stirring and cooling with an ice-water cooling bath, trifluoroacetic anhydride (2.66 mL) was added dropwise and the resulting orange solution was stirred under heating to reflux for 22 hours. Following the course of the reaction by TLC indicated that starting material was consumed by this time. The resulting brown solution was cooled to room temperature. Crushed ice was added and the pH was adjusted to 12 using 2 M aqueous NaOH (5 mL).
  • Step D A 25 mL single-necked round-bottom flask equipped with a condenser was charged with a solution of 2,4-dimethyl-5,6,7,8-tetrahydro-quinolin-8-ol (226 mg) in chloroform (2.00 mL). Under stirring, manganese(IV) oxide (443 mg) was added and the resulting black suspension was stirred under heating to reflux for 18 hours, after which time TLC indicated that no starting material was remaining. The resulting black material was purified by chromatography on silica gel (eluent: heptane / ethyl acetate gradient from 1: 1 to 1:2 (v:v)). This gave the tittle compound (78 mg) as an orange gum.
  • Step A) 9-Methyl-l,2,3,4-tetrahydroacridine In a round-bottom flask, cyclohexanone (6.1 ml_, 58 mmol) was heated at 90°C, and 2-aminoacetophenone hydrochloride (10 g; 58 mmol) was added by small fractions. The bottom flask was then equipped with a condenser, and the crude heterogeneous mixture was further heated overnight at 110°C. After cooling to room temperature, the red-orange solid was dissolved in ethanol/HCI (12 N) [95/5 v/v]. The solution was then neutralized with an aqueous NaOH solution.
  • Step B) N-Oxide-9-methyl-l,2,3,4-tetrahydroacridine A dichloromethane solution (300 ml.) of 3-chloroperbenzoic acid (26 g; 105 mmol) was slowly added to a dichloromethane solution (100 mL) of 9-methyl-l,2,3,4-tetrahydroacridine (10.2 g; 52 mmol) at 0°C. The mixture was stirred for 4 h at room temperature and quenched with an aqueous NaOH solution. The organic layers were further washed with water (5 x 100 mL) and dried over MgS0 4 , and the solvent was removed under reduced pressure giving desired product as a brownish solid.
  • the crude solid was dissolved in methanol (50 ml.) and saponified by an aqueous K 2 C0 3 solution (2 M, 150 ml_); a brown solid precipitated.
  • the methanol was removed under reduced pressure, and the product was extracted with dichloromethane (2 x 150 ml_).
  • the combined organic layers were washed with brine (2 x 50 ml_), dried over magnesium sulfate, and evaporated to dryness.
  • the desired product was recovered as a brown solid (9.4 g, 84%).
  • Step D) 9-methyl-2,3-dihydro-l/-/-acridin-4-one: To a dichloromethane solution (300 ml.) of 9-methyl-l,2,3,4-tetrahydroacridin-4-ol (9.4 g, 44 mmol) was added Mn0 2 (23 g, 264 mmol) at room temperature, and the heterogeneous solution was allowed to stir for 2 days. After filtration over Celite, the solvent was evaporated. The crude dark solid was purified by column chromatography (neutral alumina, dichloromethane as eluant). After evaporation of the solvent, the title compound was recovered as a brownish solid (5.41 g, 58%).
  • HP 1100 HPLC from Agilent solvent degasser, binary pump, heated column compartment and diode-array detector.
  • HP 1100 HPLC from Agilent solvent degasser, quaternary pump (ZCQ) / binary pump (ZDQ), heated column compartment and diode-array detector.
  • HP 1100 HPLC from Agilent solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Phenomenex Gemini C18, 3 ⁇ , 30 x 3 mm
  • Ionization method Electrospray
  • Solvent degasser binary pump, heated column compartment and diode-array detector; Column: Phenomenex Gemini C18, 3 - m, 30 x 2 mm;
  • Ionization method Electrospray
  • Phvtoohthora 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 at an application rate of 200ppm.
  • 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% relative humidity under a light regime of 24 h darkness followed by 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 in untreated check leaf disks (5 - 7 days after application).
  • the following compounds gave at least 80% control of Phytophthora infestans: P.01, P.02, P.07, P.08, P.13, P.14
  • 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% relative humidity 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 in untreated check leaf disks (6 - 8 days after application).
  • the following compounds gave at least 80% control of Plasmopara viticola: P.01, P.09, P.13
  • Wheat leaf segments cultivated variety (cv) Kanzler were placed on agar in 24-well plates and sprayed with formulated test compound diluted in water at an application rate of 200ppm.
  • 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% relative humidity 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 in untreated check leaf segments (7 - 9 days after application).
  • the following compounds gave at least 80% control of Puccinia recondita f. sp. tritici: P.01, P.02, P.03, P.05, P.06, P.07, P.08, P.09, P.10, P.12, P.13, P.14
  • Wheat leaf segments cv Kanzler were placed on agar in 24-well plates. The leaf segments were inoculated with a spore suspension of the fungus. The plates were stored in darkness at 19°C and 75% relative humidity. The formulated test compound diluted in water was applied at an application rate of 200ppm 1 day after inoculation. The leaf segments were incubated at 19°C and 75% relative humidity under a light regime of 12/12 h
  • Wheat leaf segments cv Kanzler were placed on agar in a 24-well plate and sprayed with formulated test compound diluted in water at an application rate of 200ppm.
  • 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% relative humidity 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 in untreated check leaf disks (5 - 7 days after application).
  • Barley leaf segments cv Hasso were placed on agar in a 24-well plate and sprayed with formulated test compound diluted in water at an application rate of 200ppm.
  • the leaf segments were inoculated with a spore suspension of the fungus two days after application of the test solution.
  • the inoculated leaf segments were incubated at 20°C and 65% relative humidity under a light regime of 12/12 h (light/dark) 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).
  • Botrvotinia fuckeliana (Botrvtis cinerea) I liquid culture (Gray mould):
  • 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 96-well microtiter plate at an application rate of 200ppm, 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. The following compounds gave at least 80% control of Glomerella lagenarium P.Ol, P.02, P.03, P.05, P.06, P.07, P.08, P.09, P.10, P.13, P.14
  • Mycosphaerella arachidis (Cercosoora arachidicola) I liquid culture (early leaf spot): Conidia of the fungus from cryogenic storage were directly mixed into nutrient 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 96-well microtiter plate at an application rate of 200ppm, 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. The following compounds gave at least 80% control of Mycosphaerella graminicola: P.Ol, P.02, P.03, P.04, P.05, P.06, P.07, P.08, P.09, P.10, P.ll, P.12, P.13, P.14
  • 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 96-well microtiter plate at an application rate of 200ppm, the nutrient broth Op.33, containing the fungal spores is added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application. The following compounds gave at least 80% control of Gaeumannomyces graminis: P.Ol, P.02, P.03, P.08, P.10, P.ll, P.12, P.13, P.14
  • 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 96-well microtiter plate at an application rate of 200ppm, 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.
  • nutrient broth PDB potato dextrose broth
  • Wheat leaf segments cv. Kanzler were placed on agar in a 24-well plate and sprayed with the formulated test compound diluted in water at an application rate of 200ppm.
  • 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% relative humidity under a light regime of 24 h darkness followed by 12h/12h (dark/light) 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).
  • Tomato leaf disks cultivated variety (cv.) Baby were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water at an application rate of 200ppm.
  • 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% relative humidity 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).
  • the following compounds gave at least 80% control of Alternaria solani: P.05, P.06, P.07, P.08
  • Mycelia fragments and oospores of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (potato dextrose broth). After placing a DMSO solution of test compound into a 96-well format microtiter plate at an application rate of 200ppm, the nutrient broth containing the fungal mycelia/spore mixture was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 2-3 days after application. The following compounds gave at least 80% control of Pythium ultimum: P.01, P.02, P.05, P.07, P.08, P.09, P.13, P.14
  • the leaf segments were inoculated with a spore suspension of the fungus 2 days after application.
  • the inoculated leaf segments were incubated at 22°C and 80% rh under a light regime of 24 h darkness followed by 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 in untreated check leaf segments (5 - 7 days after application).
  • the following compounds gave at least 80% control of
  • Magnaporthe grisea P.02, P.03, P.06, P.07, P.08, P.09, P.12, P.13, P.14, P.15

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Abstract

La présente invention concerne des composés de formule (I), où D1, D2, D3, G1, G2, G3, Y3, Y4, Y6, p et X sont tels que définis dans les revendications. L'invention concerne en outre des compositions contenant ces composés et leur utilisation en agriculture ou en horticulture pour prévenir ou lutter contre l'infestation des plantes par des micro-organismes phytopathogènes, de préférence des champignons.
PCT/EP2012/053444 2011-03-03 2012-02-29 Nouveaux éthers d'oxime microbiocides WO2012117021A2 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9745253B2 (en) 2015-03-13 2017-08-29 Forma Therapeutics, Inc. Alpha-cinnamide compounds and compositions as HDAC8 inhibitors
US10029995B2 (en) 2015-09-03 2018-07-24 Forma Therapeutics, Inc. [6,6] fused bicyclic HDAC8 inhibitors
CN110799498A (zh) * 2017-01-23 2020-02-14 深圳大学 一种对非靶生物体具有低毒性的新型天然灭藻剂

Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0353191A2 (fr) 1988-07-29 1990-01-31 Ciba-Geigy Ag Séquences d'ADN codant des polypeptides avec activité béta-1,3-glucanase
EP0392225A2 (fr) 1989-03-24 1990-10-17 Ciba-Geigy Ag Plantes transgéniques résistantes aux maladies
WO1995033818A2 (fr) 1994-06-08 1995-12-14 Ciba-Geigy Ag Genes pour la synthese des substances antipathogenes
WO1997033890A1 (fr) 1996-03-11 1997-09-18 Novartis Ag Derives de pyrimidine-4-one utilises comme pesticide
WO2004104007A1 (fr) 2003-05-22 2004-12-02 Pharmacia Italia S.P.A. Derives de pyrazolo-quinazoline, procede de preparation associe et leur utilisation en tant qu'inhibiteurs de kinase
US20050075366A1 (en) 2002-05-21 2005-04-07 Heidelbaugh Todd M. 4-(2-Methyl-5,6,7,8-tetrahydro-quinolin-7-ylmethyl)-1,3-dihydro-imidazole-2-thione as specific alpha2B agonist and methods of using the same
WO2006087343A1 (fr) 2005-02-16 2006-08-24 Basf Aktiengesellschaft Anilides d'acide carboxylique pyrazole, procedes de production associes et agents les contenant pour la lutte antifongique
WO2006123145A1 (fr) 2005-05-18 2006-11-23 F2G Ltd Agents antifongiques
US20070032470A1 (en) 2005-08-04 2007-02-08 Yong-Jin Wu Novel phenylcarboxyamides as beta-secretase inhibitors
WO2007048556A1 (fr) 2005-10-25 2007-05-03 Syngenta Participations Ag Dérivés d'amides hétérocycliques utiles en tant que microbiocides
WO2007058504A1 (fr) 2005-11-21 2007-05-24 Lg Life Sciences, Ltd. Nouveaux composes utilises comme agonistes des ppar gamma et des ppar alpha, procede de preparation afferent et composition pharmaceutique les renfermant
WO2007075459A2 (fr) 2005-12-16 2007-07-05 E. I. Du Pont De Nemours And Company 5-arylisoxazolines pour lutter contre des parasites invertebres
WO2008013925A2 (fr) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Amides azocycliques fongicides
WO2008074418A2 (fr) 2006-12-19 2008-06-26 Bayer Cropscience Aktengesellschaft Bisoxime utilisée comme fongicide
WO2008148570A1 (fr) 2007-06-08 2008-12-11 Syngenta Participations Ag Amides d'acide carboxylique de pyrazole utiles comme microbiocides
WO2009010488A1 (fr) 2007-07-16 2009-01-22 Novartis Ag Composés hétérocycliques utiles comme inhibiteurs de mk2
WO2009049846A1 (fr) 2007-10-16 2009-04-23 Syngenta Participations Ag Composés insecticides
WO2010123791A1 (fr) 2009-04-22 2010-10-28 E. I. Du Pont De Nemours And Company Formes solides d'un amide azocyclique
WO2011051243A1 (fr) 2009-10-29 2011-05-05 Bayer Cropscience Ag Combinaisons de composé actif
WO2011104089A1 (fr) 2010-02-25 2011-09-01 Syngenta Participations Ag Procédé de préparation de dérivés d'isoxazoline
WO2012001040A1 (fr) 2010-07-02 2012-01-05 Syngenta Participations Ag Nouveaux dérivés microbicides d'éther de dioxime

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101977504B (zh) * 2008-03-19 2014-11-26 拜尔农科股份公司 杀真菌剂肟基-四唑衍生物
JP2012162460A (ja) * 2009-05-27 2012-08-30 Nippon Soda Co Ltd 含窒素ヘテロアリール誘導体および農園芸用殺菌剤

Patent Citations (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0353191A2 (fr) 1988-07-29 1990-01-31 Ciba-Geigy Ag Séquences d'ADN codant des polypeptides avec activité béta-1,3-glucanase
EP0392225A2 (fr) 1989-03-24 1990-10-17 Ciba-Geigy Ag Plantes transgéniques résistantes aux maladies
WO1995033818A2 (fr) 1994-06-08 1995-12-14 Ciba-Geigy Ag Genes pour la synthese des substances antipathogenes
WO1997033890A1 (fr) 1996-03-11 1997-09-18 Novartis Ag Derives de pyrimidine-4-one utilises comme pesticide
US20050075366A1 (en) 2002-05-21 2005-04-07 Heidelbaugh Todd M. 4-(2-Methyl-5,6,7,8-tetrahydro-quinolin-7-ylmethyl)-1,3-dihydro-imidazole-2-thione as specific alpha2B agonist and methods of using the same
WO2004104007A1 (fr) 2003-05-22 2004-12-02 Pharmacia Italia S.P.A. Derives de pyrazolo-quinazoline, procede de preparation associe et leur utilisation en tant qu'inhibiteurs de kinase
WO2006087343A1 (fr) 2005-02-16 2006-08-24 Basf Aktiengesellschaft Anilides d'acide carboxylique pyrazole, procedes de production associes et agents les contenant pour la lutte antifongique
WO2006123145A1 (fr) 2005-05-18 2006-11-23 F2G Ltd Agents antifongiques
US20070032470A1 (en) 2005-08-04 2007-02-08 Yong-Jin Wu Novel phenylcarboxyamides as beta-secretase inhibitors
WO2007048556A1 (fr) 2005-10-25 2007-05-03 Syngenta Participations Ag Dérivés d'amides hétérocycliques utiles en tant que microbiocides
WO2007058504A1 (fr) 2005-11-21 2007-05-24 Lg Life Sciences, Ltd. Nouveaux composes utilises comme agonistes des ppar gamma et des ppar alpha, procede de preparation afferent et composition pharmaceutique les renfermant
WO2007075459A2 (fr) 2005-12-16 2007-07-05 E. I. Du Pont De Nemours And Company 5-arylisoxazolines pour lutter contre des parasites invertebres
WO2008013925A2 (fr) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Amides azocycliques fongicides
WO2008013622A2 (fr) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Amides azocycliques fongicides
WO2008074418A2 (fr) 2006-12-19 2008-06-26 Bayer Cropscience Aktengesellschaft Bisoxime utilisée comme fongicide
WO2008148570A1 (fr) 2007-06-08 2008-12-11 Syngenta Participations Ag Amides d'acide carboxylique de pyrazole utiles comme microbiocides
WO2009010488A1 (fr) 2007-07-16 2009-01-22 Novartis Ag Composés hétérocycliques utiles comme inhibiteurs de mk2
WO2009049846A1 (fr) 2007-10-16 2009-04-23 Syngenta Participations Ag Composés insecticides
WO2010123791A1 (fr) 2009-04-22 2010-10-28 E. I. Du Pont De Nemours And Company Formes solides d'un amide azocyclique
WO2011051243A1 (fr) 2009-10-29 2011-05-05 Bayer Cropscience Ag Combinaisons de composé actif
WO2011104089A1 (fr) 2010-02-25 2011-09-01 Syngenta Participations Ag Procédé de préparation de dérivés d'isoxazoline
WO2012001040A1 (fr) 2010-07-02 2012-01-05 Syngenta Participations Ag Nouveaux dérivés microbicides d'éther de dioxime

Non-Patent Citations (105)

* Cited by examiner, † Cited by third party
Title
"Angewandte Chemie", vol. 43, 2004, INTERNATIONAL EDITION, pages: 3333 - 3336
"Chem. Ber.", 1971, pages: 2975
"Handbook of Organopalladium Chemistry for Organic Synthesis", vol. 1, 2002, pages: 493 - 529
"March's Advanced Organic Chemistry: Reaction, Mechanisms and Structure", 2007
ADVANCED SYNTHESIS & CATALYSIS, vol. 346, no. 13-15, 2004, pages 1798 - 1811
ARCHIV DER PHARMAZIE, vol. 340, no. 4, 2007, pages 202 - 208
BARK, THOMAS; THUMMEL, RANDOLPH P., INORGANIC CHEMISTRY, vol. 44, no. 24, 2005, pages 8733 - 8739
BIOINORGANIC CHEMISTRY AND APPLICATIONS, vol. 1, no. 3-4, pages 299 - 308,2003
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 12, no. 3, 2002, pages 341 - 344
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 15, no. 12, 2005, pages 2990 - 2993
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 18, no. 24, 2008, pages 6471 - 6475
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, no. 10, 2009, pages 2654 - 2660
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, no. 10, 2009, pages 2683 - 2687
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, no. 13, 2009, pages 3627 - 3631
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, no. 19, 2009, pages 5689 - 5692
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, no. 8, 2009, pages 2277 - 2281
BIOORGANIC & MEDICINAL CHEMISTRY, vol. 11, no. 18, 2003, pages 4015 - 4026
BIOORGANIC & MEDICINAL CHEMISTRY, vol. 17, no. 18, 2009, pages 6651 - 6658
BIOORGANIC & MEDICINAL CHEMISTRY, vol. 9, no. 11, 2001, pages 2863 - 2870
C. D. S. TOMLIN: "The Pesticide Manual - A World Compendium", THE BRITISH CROP PROTECTION COUNCIL, article "The Pesticide Manual"
CHEM. EUR. J., vol. 15, 2009, pages 6811 - 6814
CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 51, no. 2, 2003, pages 138 - 151
CHEMICAL COMMUNICATIONS, 2009, pages 5618 - 5620
CHEMISTRY & BIOLOGY, vol. 9, no. 1, 2002, pages 113 - 129
CHEMISTRY-A EUROPEAN JOURNAL, vol. 15, no. 20, 2009, pages 5006 - 5011
CHEMISTRY-A EUROPEAN JOURNAL, vol. 16, no. 1, 2010, pages 89 - 94,S89,1-S89,10
CHINESE JOURNAL OF CHEMISTRY, vol. 27, no. 1, 2009, pages 33 - 42
CRAWFORD, JASON B.; CHEN, GANG; GAUTHIER, DAVID; WILSON, TREVOR; CARPENTER, BRYON; BAIRD, IAN R.; MCEACHERN, ERNIE; KALLER, ALAN;, ORGANIC PROCESS RESEARCH & DEVELOPMENT, vol. 12, no. 5, 2008, pages 823 - 830
EJEAFCHE, ELECTRONIC JOURNAL OF ENVIRONMENTAL, AGRICULTURAL AND FOOD CHEMISTRY, vol. 5, no. 5, 2006, pages 1515 - 1521
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, 2008, pages 4101 - 4110
GREENE, T. W.; WUTS, P. G. N.: "Protective Groups in Organic Synthesis", 2006, JOHN WILEY & SONS, INC
HETEROCYCLES, vol. 80, no. 1, pages 359 - 368
J. AM. CHEM. SOC., vol. 128, 2006, pages 1243 - 12255
J. HETEROCYCL. CHEM., vol. 20, 1983, pages 649 - 653
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 38, no. 3, 1990, pages 839 - 44
JOURNAL OF ANTIBIOTICS, vol. 61, no. 10, 2008, pages 603 - 614
JOURNAL OF COMBINATORIAL CHEMISTRY, vol. 7, no. 4, 2005, pages 517 - 519
JOURNAL OF COMBINATORIAL CHEMISTRY, vol. 7, no. 6, 2005, pages 958 - 967
JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 46, no. 1, 2009, pages 116 - 118
JOURNAL OF MED. CHEM., vol. 52, no. 16, pages 5152 - 5163
JOURNAL OF MEDICINAL CHEMISTRY, vol. 20, no. 5, 1977, pages 718 - 21
JOURNAL OF MEDICINAL CHEMISTRY, vol. 32, no. 8, 1989, pages 1820 - 35
JOURNAL OF MEDICINAL CHEMISTRY, vol. 44, no. 21, 2001, pages 3339 - 3342
JOURNAL OF MEDICINAL CHEMISTRY, vol. 49, no. 17, 2006, pages 5177 - 5186
JOURNAL OF MEDICINAL CHEMISTRY, vol. 50, no. 26, 2007, pages 6535 - 6544
JOURNAL OF MEDICINAL CHEMISTRY, vol. 51, no. 15, 2008, pages 4601 - 4608
JOURNAL OF MEDICINAL CHEMISTRY, vol. 51, no. 22, 2008, pages 7193 - 7204
JOURNAL OF MEDICINAL CHEMISTRY, vol. 51, no. 6, 2008, pages 1719 - 1729
JOURNAL OF MEDICINAL CHEMISTRY, vol. 53, no. 3, 2010, pages 1200 - 1210
JOURNAL OF ORGANIC CHEMISTRY, vol. 52, no. 22, 1987, pages 4978 - 84
JOURNAL OF ORGANIC CHEMISTRY, vol. 53, no. 2, 1988, pages 386 - 90
JOURNAL OF ORGANIC CHEMISTRY, vol. 69, no. 6, 2004, pages 1959 - 1966
JOURNAL OF ORGANIC CHEMISTRY, vol. 70, no. 17, 2005, pages 6995 - 6998
JOURNAL OF ORGANIC CHEMISTRY, vol. 72, no. 20, 2007, pages 7783 - 7786
JOURNAL OF ORGANIC CHEMISTRY, vol. 73, no. 11, 2008, pages 4017 - 4026
JOURNAL OF ORGANIC CHEMISTRY, vol. 73, no. 12, 2008, pages 4491 - 4495
JOURNAL OF ORGANIC CHEMISTRY, vol. 73, no. 5, 2008, pages 2007 - 2010
JOURNAL OF ORGANIC CHEMISTRY, vol. 74, no. 11, 2009, pages 4166 - 4176
JOURNAL OF ORGANIC CHEMISTRY, vol. 74, no. 12, 2009, pages 4646 - 4649
JOURNAL OF ORGANIC CHEMISTRY, vol. 74, no. 15, 2009, pages 5750 - 5753
JOURNAL OF ORGANIC CHEMISTRY, vol. 74, no. 16, 2009, pages 6072 - 6076
JOURNAL OF ORGANIC CHEMISTRY, vol. 75, no. 2, 2010, pages 424 - 433
JOURNAL OF ORGANOMETALLIC CHEMISTRY, vol. 333, no. 2, 1987, pages 139 - 53
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 129, no. 3, 2007, pages 490 - 491
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 130, no. 12, 2008, pages 4196 - 4201
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 130, no. 38, 2008, pages 12592 - 12593
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 131, no. 20, 2009, pages 6961 - 6963
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 131, no. 34, 2009, pages 12344 - 12353
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 132, no. 8, 2010, pages 2532 - 2533
MCEACHERN, E. J.; YANG, W.; CHEN, G.; SKERLJ, R. T.; BRIDGER, G. J., SYNTHETIC COMMUNICATIONS, vol. 33, no. 20, 2003, pages 3497 - 350
ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 6, no. 21, 2008, pages 4036 - 4040
ORGANIC LETTERS, vol. 10, no. 2, 2008, pages 285 - 288
ORGANIC LETTERS, vol. 11, no. 2, 2009, pages 345 - 347
ORGANIC LETTERS, vol. 11, no. 20, 2009, pages 4540 - 4543
ORGANIC LETTERS, vol. 11, no. 9, 2009, pages 2019 - 2022
ORGANIC LETTERS, vol. 6, no. 26, 2004, pages 4905 - 4907
ORGANIC LETTERS, vol. 9, no. 6, 2007, pages 1169 - 1171
ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL, vol. 26, no. 1, 1994, pages 111 - 13
ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL, vol. 32, no. 2, 2000, pages 153 - 159
ORGANOMETALLICS, vol. 5, no. 2, 1986, pages 348 - 55
PROC. BCPC, INT. CONGR, vol. 1, 2003, pages 93
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY, vol. 42, no. 5, 2006, pages 735 - 738
SCIENTIA PHARMACEUTICA, vol. 66, no. 1, 1998, pages 9 - 21
SYNLETT, 2008, pages 3036 - 3040
SYNTHESIS, 1964, pages 3397
SYNTHESIS, 1964, pages 3407
SYNTHESIS, 1981, pages 283 - 5
SYNTHESIS, 1996, pages 1012 - 1018
SYNTHESIS, 2010, pages 85 - 90
SYNTHESIS, 2010, pages 91 - 97
SYNTHETIC COMMUN., vol. 10, no. 28, 1998, pages 1743 - 1753
SYNTHETIC COMMUNICATIONS, vol. 19, no. 18, 1989, pages 3129 - 38
SYNTHETIC COMMUNICATIONS, vol. 27, no. 14, 1997, pages 2521 - 2526
SYNTHETIC COMMUNICATIONS, vol. 28, no. 14, 1998, pages 2621 - 2633
SYNTHETIC COMMUNICATIONS, vol. 37, no. 7, 2007, pages 1155 - 1165
TETRAHEDRON LETT, 1986, pages 2567
TETRAHEDRON LETT, 1994, pages 2255 - 2264
TETRAHEDRON LETTERS, vol. 48, no. 4, 2007, pages 647 - 650
TETRAHEDRON LETTERS, vol. 50, no. 38, 2009, pages 5329 - 5331
TETRAHEDRON LETTERS, vol. 50, no. 49, 2009, pages 6818 - 6822
TETRAHEDRON LETTERS, vol. 51, no. 19, 2010, pages 2657 - 2659
TETRAHEDRON LETTERS, vol. 51, no. 2, 2010, pages 357 - 359
TETRAHEDRON, vol. 63, no. 26, 2007, pages 6015 - 6034
TETRAHEDRON, vol. 64, no. 29, 2008, pages 7008 - 7014
TETRAHEDRON: ASYMMETRY, vol. 8, no. 2, 1997, pages 253 - 263

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